(SAGARPA 15/8/12)
Para mantener seguro el abasto, el SENASICA ha
otorgado a 385 granjas libres del virus seis mil 865 certificados zoosanitarios
de movilización para huevo fértil, huevo industrial, huevo para plato, harinas,
yema líquida y aves vivas, entre otros derivados de ave.
El Servicio Nacional de Sanidad, Inocuidad y
Calidad Agroalimentaria (SENASICA) informó que se han aplicado 80 millones de
dosis de vacuna contra la Influenza Aviar AH7N3 en la región de Los Altos de
Jalisco, con lo que se cumple la primera etapa de vacunación prevista en las
granjas avícolas.
A siete semanas de haber iniciado el Dispositivo
Nacional de Emergencia de Sanidad Animal (DINESA) para controlar y erradicar la
enfermedad se han revisado 426 granjas, ubicadas en 45 municipios de la región,
de las que 385 están libres del virus; el número de positivas se mantiene en
41, igual que lo reportado desde hace dos semanas.
El Director en Jefe del SENASICA, Enrique Sánchez
Cruz, manifestó que con base en el Programa Nacional de Vigilancia
Epidemiológica se ha contenido el virus en la región referida.
Con la finalidad de mantener el abasto a la
población, detalló, se han otorgado seis mil 865 certificados zoosanitarios de
movilización para huevo fértil, huevo industrial, huevo para plato, harinas,
yema líquida y aves vivas, entre otros derivados.
“Las granjas libres del virus han tenido
facilidades para la movilización de sus productos hacia los principales mercados
de abasto”, subrayó.
Destacó que se mantiene la cuarentena en la zona de
riesgo y el aislamiento precautorio, así como el control de la movilización
para evitar la diseminación del virus.
Una medida de control para evitar la diseminación
de la enfermedad es el sacrificio sanitario, que hasta la fecha se mantiene en
ocho millones de aves que dieron positivo al AH7N3.
Puntualizó que, a través del Programa Nacional de
Vigilancia Epidemiológica, se han recabado y analizado 11 mil 253 muestras en
granjas ubicadas en 20 estados del país, que han arrojado resultados negativos
al aislamiento viral, lo que evidencia científicamente que el brote sigue
contenido en la zona de Los Altos de Jalisco, donde se originó.
Sánchez Cruz reiteró que la presencia del virus no
implica ningún riesgo para la salud humana, por lo que las medidas de control
aplicadas por el DINESA tienen el propósito de proteger la producción avícola
de la zona.
|
Web of Knowledge
|
||
|
Record 1 of 40
|
||
|
Walker, Patrick; Cauchemez, Simon; Hartemink, Nienke; Tiensin,
Thanawat; Ghani, Azra C.
|
||
|
Outbreaks of H5N1 in poultry in Thailand: the relative role of poultry
production types in sustaining transmission and the impact of active
surveillance in control
|
||
|
JOURNAL OF THE ROYAL SOCIETY INTERFACE 9(73) 1836-1845 AUG 7 2012
|
||
|
H5N1, highly pathogenic avian influenza, continues to pose a public
health risk in the countries of southeast Asia where it has become endemic.
However, in Thailand, which experienced two of the largest recorded epidemics
in 2004-2005, the disease has been successfully reduced to very low levels.
We fitted a spatio-temporal model of the spread of infection to outbreak data
collected during the second wave of outbreaks to assess the extent to which
different poultry types were responsible for propagating infection. Our
estimates suggest that the wave of outbreaks would not have been possible
without the contribution of backyard flocks to the susceptibility of a
sub-district. However, we also estimated that outbreaks involving commercial
poultry, a much larger sector in Thailand than in neighbouring countries, were
disproportionately infectious, a factor which was also crucial in sustaining
the wave. As a result, implemented measures that aim to reduce the role of
commercial farms in the spread of infection, such as the drive to bring
aspects of the supply chain 'in house', may help to explain the subsequent
success in controlling H5N1 in Thailand. We also found that periods of active
surveillance substantially improved the rate of outbreak detection.
|
||
|
ISSN: 1742-5689
|
||
|
Record 2 of 40
|
|
Koopmans, M.; de Bruin, E.; Godeke, G-J;
Friesema, I.; van Gageldonk, R.; Schipper, M.; Meijer, A.; van Binnendijk,
R.; Rimmelzwaan, G. F.; de Jong, M. D.; Buisman, A.; van Beek, J.; van de
Vijver, D.; Reimerink, J.
|
|
Profiling of humoral immune responses to influenza viruses by using protein
microarray
|
|
CLINICAL MICROBIOLOGY AND INFECTION 18(8) 797-807. AUG 2012
|
|
Clin Microbiol Infect Abstract The emergence of pandemic A(H1N1) 2009
influenza showed the importance of rapid assessment of the degree of immunity
in the population, the rate of asymptomatic infection, the spread of
infection in households, effects of control measures, and ability of
candidate vaccines to produce a response in different age groups. A
limitation lies in the available assay repertoire: reference standard methods
for measuring antibodies to influenza virus are haemagglutination inhibition
(HI) assays and virus neutralization tests. Both assays are difficult to
standardize and may be too specific to assess possible partial humoral
immunity from previous exposures. Here, we describe the use of
antigen-microarrays to measure antibodies to HA1 antigens from seven recent
and historical seasonal H1, H2 and H3 influenza viruses, the A(H1N1) 2009
pandemic influenza virus, and three avian influenza viruses. We assessed antibody
profiles in 18 adult patients infected with A(H1N1) 2009 influenza virus
during the recent pandemic, and 21 children sampled before and after the
pandemic, against background reactivity observed in 122 persons sampled in
2008, a season dominated by seasonal A(H1N1) influenza virus. We show that
subtype-specific and variant-specific antibody responses can be measured,
confirming serological responses measured by HI. Comparison of profiles from
persons with similar HI response showed that the magnitude and broadness of
response to individual influenza subtype antigens differs greatly between
individuals. Clinical and vaccination studies, but also exposure studies,
should take these findings into consideration, as they may indicate some
level of humoral immunity not measured by HI assays.
|
|
ISSN: 1198-743X
|
|
Record 3 of 40
|
|
Abdelwhab, E. M.; Arafa, Abdel-Satar; Stech, Juergen; Grund,
Christian; Stech, Olga; Graeber-Gerberding, Marcus; Beer, Martin; Hassan,
Mohamed K.; Aly, Mona M.; Harder, Timm C.; Hafez, Hafez M.
|
|
Diversifying evolution of highly pathogenic H5N1 avian influenza virus
in Egypt from 2006 to 2011
|
|
VIRUS GENES 45(1) 14-23. AUG 2012
|
|
An evolutionary analysis was conducted of 354 hemagglutinin (HA) and
208 neuraminidase (NA) genes, including newly generated sequences of 5 HA and
30 NA, of Egyptian H5N1 clade 2.2.1 viruses isolated from poultry and humans.
Five distinct phylogenetically distinguishable clusters arose from a
monophyletic origin since 2006. Only two clusters remained in circulation after
2009: (i) A cluster of viruses arose in 2007 in industrial-vaccinated
chickens and carried multiple mutations in or adjacent to the immunogenic
epitopes of the HA. Viruses within this cluster evolved with significantly
elevated mutation rates indicating persisting selective pressures, e.g. to
escape host immunity and (ii) The second group arose in 2008 and harboured
strains from recent human infections featuring a conspicuous deletion in the
HA receptor-binding domain and substitutions close to the highly conserved
active site of the NA. In both sublineages, a number of positively selected
amino acids, different glycosylation patterns and variations in the polybasic
proteolytic cleavage site were observed. Continuous monitoring of the
evolving H5N1 virus in Egypt is essential to develop new control campaigns in
poultry and human population.
|
|
ISSN: 0920-8569
|
|
Record 4 of 40
|
|
Chen, Feng; Yan, Zhuan-Qiang; Liu, Jun; Ji, Jun;
Chang, Shuang; Liu, Di; Qin, Jian-Ping; Ma, Jing-Yun; Bi, Ying-Zuo; Xie,
Qing-Mei
|
|
Phylogenetic analysis of hemagglutinin genes of 40 H9N2 subtype avian
influenza viruses isolated from poultry in China from 2010 to 2011
|
|
VIRUS GENES 45(1) 69-75. AUG 2012
|
|
Avian influenza virus (H9N2) infection is a major problem of product
performance in poultry worldwide. Vaccination is used to limit spread, but
more knowledge is needed on the epidemiology of virus subtypes to improve
vaccine design. In this study, 40 H9N2 subtype avian influenza viruses (AIVs)
were isolated from vaccinated poultry flocks in China from 2010 to 2011.
Hemagglutinin (HA) from different virus strains was sequenced and analyzed.
We found that the HA genes of these strains shared nucleotide and deduced
amino acid homologies that ranged from 90.1 to 92.9 and 91.4 to 95.0 %, respectively,
when compared with vaccine strains. Phylogenetic analysis showed that the
strains tested could be divided into two major groups. Group I consisted of
24 strains isolated mainly from Eastern and Central China. Group II consisted
of 20 strains isolated from Southern China. The cleavage site within the HA
protein contained two basic motifs, PSRSSRa dagger"GLF for group I, and
PARSSRa dagger"GLF for group II. Additional potential glycosylation
sites were found at amino acid position 295 in the HA1 of the isolates in
group I, compared with isolates in group II and the vaccine strains.
Furthermore, 38 out of the 40 isolates had a leucine residue at position 216
(aa 226 in H3), which was characteristic of human influenza virus-like
receptor specificity. In the present study we found that geographical factors
play a significant role in virus evolution, and emphasize the importance of
continuing surveillance of H9N2 AIVs in chickens in China.
|
|
ISSN: 0920-8569
|
|
Record 5 of 40
|
|
Vergara-Alert, Julia; Argilaguet, Jordi M.;
Busquets, Nuria; Ballester, Maria; Martin-Valls, Gerard E.; Rivas, Raquel;
Lopez-Soria, Sergio; Solanes, David; Majo, Natalia; Segales, Joaquim;
Veljkovic, Veljko; Rodriguez, Fernando; Darji, Ayub
|
|
Conserved Synthetic Peptides from the Hemagglutinin of Influenza
Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model
|
|
PLOS ONE 7(7). JUL 16 2012
|
|
Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have
recently become an increasing threat to cause potential pandemics. Pigs have
an important role in this aspect. As reflected in the 2009 human H1N1
pandemia, they may act as a vehicle for mixing and generating new assortments
of viruses potentially pathogenic to animals and humans. Lack of universal
vaccines against the highly variable influenza virus forces scientists to
continuously design vaccines a la carte, which is an expensive and risky
practice overall when dealing with virulent strains. Therefore, we focused
our efforts on developing a broadly protective influenza vaccine based on the
Informational Spectrum Method (ISM). This theoretical prediction allows the
selection of highly conserved peptide sequences from within the hemagglutinin
subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the
flanking region of the HA binding site and with the potential to elicit
broader immune responses than conventional vaccines. Confirming the
theoretical predictions, immunization of conventional farm pigs with the
synthetic peptides induced humoral responses in every single pig. The fact
that the induced antibodies were able to recognize in vitro heterologous
influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine
influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic
avian virus, confirm the broad recognition of the antibodies induced.
Unexpectedly, all pigs also showed T-cell responses that not only recognized
the specific peptides, but also the pH1N1 virus. Finally, a partial effect on
the kinetics of virus clearance was observed after the intranasal infection
with the pH1N1 virus, setting forth the groundwork for the design of
peptide-based vaccines against influenza viruses. Further insights into the
understanding of the mechanisms involved in the protection afforded will be
necessary to optimize future vaccine formulations.
|
|
ISSN: 1932-6203
|
|
Record 6 of 40
|
|
Jazayeri, Seyed Davoud; Ideris, Aini; Zakaria,
Zunita; Shameli, Kamyar; Moeini, Hassan; Omar, Abdul Rahman
|
|
Cytotoxicity and immunological responses following oral vaccination of
nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis
silver nanoparticles
|
|
JOURNAL OF CONTROLLED RELEASE 161(1) 116-123. JUL 10 2012
|
|
DNA formulations provide the basis for safe and cost effective
vaccine. Low efficiency is often observed in the delivery of DNA vaccines. In
order to assess a new strategy for oral DNA vaccine formulation and delivery,
plasmid encoding hemagglutinin (HA) gene of avian influenza virus,
A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1/H5) was formulated using green
synthesis of sliver nanoparticles (AgNP) with polyethylene glycol (PEG). AgNP
were successfully synthesized uniformly dispersed with size in the range of 4
to 18 nm with an average size of 11 nm. Cytotoxicity of the prepared AgNP was
investigated in vitro and in vivo using MCF-7 cells and cytokine expression,
respectively. At the concentration of -5 log(10)AgNP, no cytotoxic effects
were detected in MCF-7 cells with 9.5% cell death compared to the control.
One-day-old specific pathogen-free (SPF) chicks immunized once by oral gavage
with 10 mu l of pcDNA3.1/H5 (200 ng/ml) nanoencapsulated with 40 mu l AgNP
(3.7x10(-2) mu g of Ag) showed no clinical manifestations. PCR successfully
detect the AgNP/H5 plasmid from the duodenum of the inoculated chicken as
early as 1 h post-immunization. Immunization of chickens with AgNP/H5
enhanced both pro inflammatory and Th1-like expressions, although no
significant differences were recorded in the chickens inoculated with AgNP,
AgNP/pcDNA3.1 and the control. In addition, serum samples collected from
immunized chickens with AgNP/H5 showed rapidly increasing antibody against H5
on day 14 after immunization. The highest average antibody titres were
detected on day 35 post-immunization at 51.2 +/- 7.5. AgNP/H5 also elicited
both CD4+ and CD8+ T cells in the immunized chickens as early as day 14 after
immunization, at 7.5 +/- 2.0 and 20 +/- 1.9 percentage, respectively. Hence,
single oral administrations of AgNP/H5 led to induce both the antibody and
cell-mediated immune responses as well as enhanced cytokine production. (C)
2012 Elsevier B.V. All rights reserved.
|
|
ISSN: 0168-3659
|
|
Record 7 of 40
|
|
Marcelin, Glendie; Sandbulte, Matthew R.; Webby, Richard J.
|
|
Contribution of antibody production against neuraminidase to the protection
afforded by influenza vaccines
|
|
REVIEWS IN MEDICAL VIROLOGY 22(4) 267-279. JUL 2012
|
|
Vaccines are instrumental in controlling the burden of influenza virus
infection in humans and animals. Antibodies raised against both major viral
surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), can
contribute to protective immunity. Vaccine-induced HA antibodies have been
characterized extensively, and they generally confer protection by blocking
the attachment and fusion of a homologous virus onto host cells. Although not
as well characterized, some functions of NA antibodies in influenza
vaccine-mediated immunity have been recognized for many years. In this
review, we summarize the case for NA antibodies in influenza vaccine-mediated
immunity. In the absence of well-matched HA antibodies, NA antibodies can
provide varying degrees of protection against disease. NA proteins of
seasonal influenza vaccines have been shown in some instances to elicit serum
antibodies with cross-reactivity to avian-origin and swine-origin influenza
strains, in addition to HA drift variants. NA-mediated immunity has been
linked to (i) conserved NA epitopes amongst otherwise antigenically distinct
strains, partly attributable to the segmented influenza viral genome; (ii) inhibition
of NA enzymatic activity; and (iii) the NA content in vaccine formulations.
There is a potential to enhance the effectiveness of existing and future
influenza vaccines by focusing greater attention on the antigenic
characteristics and potency of the NA protein. Copyright (c) 2012 John Wiley
& Sons, Ltd.
|
|
ISSN: 1052-9276
|
|
Record 8 of 40
|
|
Pearce, Melissa B.; Belser, Jessica A.; Gustin,
Kortney M.; Pappas, Claudia; Houser, Katherine V.; Sun, Xiangjie; Maines,
Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.; Tumpey, Terrence
M.
|
|
Seasonal Trivalent Inactivated Influenza Vaccine Protects against 1918
Spanish Influenza Virus Infection in Ferrets
|
|
JOURNAL OF VIROLOGY 86(13) 7118-7125. JUL 2012
|
|
The influenza virus H1N1 pandemic of 1918 was one of the worst medical
catastrophes in human history. Recent studies have demonstrated that the
hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus
[A(H1N1)pdm09], the latter now a component of the seasonal trivalent
inactivated influenza vaccine (TIV), share cross-reactive antigenic
determinants. In this study, we demonstrate that immunization with the
2010-2011 seasonal TIV induces neutralizing antibodies that cross-react with
the reconstructed 1918 pandemic virus in ferrets. TIV-immunized ferrets
subsequently challenged with the 1918 virus displayed significant reductions
in fever, weight loss, and virus shedding compared to these parameters in
nonimmune control ferrets. Seasonal TIV was also effective in protecting
against the lung infection and severe lung pathology associated with 1918
virus infection. Our data demonstrate that prior immunization with
contemporary TIV provides cross-protection against the 1918 virus in ferrets.
These findings suggest that exposure to A(H1N1)pdm09 through immunization may
provide protection against the reconstructed 1918 virus which, as a select
agent, is considered to pose both biosafety and biosecurity threats.
|
|
ISSN: 0022-538X
|
|
Record 9 of 40
|
|
Sakoda, Yoshihiro; Okamatsu, Masatoshi; Isoda,
Norikazu; Yamamoto, Naoki; Ozaki, Koichi; Umeda, Yasuto; Aoyama, Shigeyuki;
Kida, Hiroshi
|
|
Purification of human and avian influenza viruses using cellulose
sulfate ester (Cellufine Sulfate) in the process of vaccine production
|
|
MICROBIOLOGY AND IMMUNOLOGY 56(7) 490-495. JUL 2012
|
|
Affinity chromatography using sulfated, spherical cellulose beads
(Cellufine Sulfate) was assessed for purification of influenza A and
influenza B viruses. Recovery rates of viruses eluted from the beads were
high for all tested virus strains. This method was also useful for removing
chicken egg-derived impurities from allantoic fluids containing influenza
viruses; the hemagglutination activity per amount of protein in the eluted
sample was significantly higher than that in the applied sample. These
results suggest that use of Cellufine Sulfate is a practical method for
primary purification of influenza viruses in the process of influenza vaccine
production.
|
|
ISSN: 0385-5600
|
|
Record 10 of 40
|
|
Wang ZhaoGuo; Jiang WenMing; Liu Shuo; Hou GuangYu;
Li JinPing; Wang ZhiYu; Chen JiMing
|
|
Increased substitution rate in H5N1 avian influenza viruses during
mass vaccination of poultry
|
|
CHINESE SCIENCE BULLETIN 57(19) 2419-2424. JUL 2012
|
|
As a means of heated debate, mass vaccination of poultry has been used
in some countries to control H5N1 highly pathogenic avian influenza (HPAI),
which remains of global economic and public health significance.
Theoretically, mass vaccination can act as an evolutionary selective force
facilitating the emergence of vaccine-resistant viruses, similar to that
widespread use of antibiotics facilitates the emergence of
antibiotic-resistant bacteria. To support the hypothesis, the substitution
rates in the two subunits, HA1 and HA2, of the viral hemagglutinin gene, were
calculated using a Bayesian Markov Chain Monte Carlo (MCMC) approach. It was
found that the rate in the HA1 subunit, but not in the HA2 subunit, increased
significantly during periods of mass vaccination (2005-2010 in China and
2003-2009 in Indonesia), in contrast to the periods when no mass vaccination
programs took place (1996-2004 in China and 2004-2008 in Thailand). Because
substitutions in the HA1 subunit rather than in the HA2 subunit can lead to
vaccine-resistant viruses, the results support that mass vaccination programs
facilitate the emergence of vaccine-resistant viruses, which, in turn, will
render mass vaccination programs less effective. Therefore, caution must be
taken when adopting mass vaccination as a long-term strategy to control HPAI.
|
|
ISSN: 1001-6538
|
|
Record 11 of 40
|
|
Chittaganpitch, Malinee; Supawat, Krongkaew;
Olsen, Sonja J.; Waicharoen, Sunthareeya; Patthamadilok, Sirima; Yingyong,
Thitipong; Brammer, Lynnette; Epperson, Scott P.; Akrasewi, Passakorn;
Sawanpanyalert, Pathom
|
|
Influenza viruses in Thailand: 7 years of sentinel surveillance data,
2004-2010
|
|
INFLUENZA AND OTHER RESPIRATORY VIRUSES 6(4) 276-283. JUL 2012
|
|
Please cite this paper as: Chittaganpitch et similar to al. (2012)
Influenza viruses in Thailand: 7 years of sentinel surveillance data,
20042010. Influenza and Other Respiratory Viruses 6(4), 276283. Background
The re-emergence of avian influenza A (H5N1) in 2004 and the pandemic of
influenza A (H1N1) in 2009 highlight the need for routine surveillance
systems to monitor influenza viruses, particularly in Southeast Asia where
H5N1 is endemic in poultry. In 2004, the Thai National Institute of Health,
in collaboration with the US Centers for Disease Control and Prevention,
established influenza sentinel surveillance throughout Thailand. Objectives
To review routine epidemiologic and virologic surveillance for influenza
viruses for public health action. Methods Throat swabs from persons with
influenza-like illness and severe acute respiratory illness were collected at
11 sentinel sites during 20042010. Influenza viruses were identified using
the standard protocol for polymerase chain reaction. Viruses were cultured
and identified by immunofluorescence assay; strains were identified by
hemagglutination inhibition assay. Data were analyzed to describe frequency,
seasonality, and distribution of circulating strains. Results Of the 19 457
throat swabs, 3967 (20%) were positive for influenza viruses: 2663 (67%) were
influenza A and able to be subtyped [21% H1N1, 25% H3N2, 21% pandemic (pdm)
H1N1] and 1304 (33%) were influenza B. During 20092010, the surveillance
system detected three waves of pdm H1N1. Influenza annually presents two
peaks, a major peak during the rainy season (June August) and a minor peak in
winter (Octobe February). Conclusions These data suggest that March April may
be the most appropriate months for seasonal influenza vaccination in
Thailand. This system provides a robust profile of the epidemiology of
influenza viruses in Thailand and has proven useful for public health
planning.
|
|
ISSN: 1750-2640
|
|
Record 12 of 40
|
|
Wodal, Walter; Falkner, Falko G.; Kerschbaum,
Astrid; Gaiswinkler, Claudia; Fritz, Richard; Kiermayr, Stefan; Portsmouth,
Daniel; Savidis-Dacho, Helga; Coulibaly, Sogue; Piskernik, Christina;
Hohenadl, Christine; Howard, M. Keith; Kistner, Otfried; Barrett, P. Noel;
Kreil, Thomas R.
|
|
A cell culture-derived whole-virus H9N2 vaccine induces high titer
antibodies against hemagglutinin and neuraminidase and protects mice from
severe lung pathology and weight loss after challenge with a highly virulent
H9N2 isolate
|
|
VACCINE 30(31) 4625-4631. JUL 2012
|
|
Background: Influenza viruses of subtype A/H9N2 are enzootic in
poultry across Asia and the Middle East and are considered to have pandemic
potential. The development of new vaccine manufacturing technologies is a
cornerstone of influenza pandemic preparedness.
Methods: A non-adjuvanted whole-virus H9N2 vaccine was developed using Vero cell culture manufacturing technology. The induction of hemagglutination inhibition (HI) and virus-neutralizing antibodies was assessed in CD1 mice and guinea pigs. A highly sensitive enzyme-linked lectin assay was used to investigate the induction of antibodies capable of inhibiting the enzymatic activity of the H9N2 neuraminidase. Protective efficacy against virus replication in the lung after challenge with the homologous virus was evaluated in BALB/c mice by a TCID50 assay, and prevention of virus replication in the lung and associated pathology were evaluated by histology and immunohistochemistry. To investigate the ability of the vaccine to prevent severe disease, BALB/c mice were challenged with a highly virulent mouse-adapted H9N2 isolate which was generated by multiple lung-to-lung passage of wild-type virus. Results: The vaccine elicited high titers of functional H9N2-specific HA antibodies in both mice and guinea pigs, as determined by HI and virus neutralization assays. High titer H9N2-specific neuraminidase inhibiting (NAi) antibodies were also induced in both species. Vaccinated mice were protected from lung virus replication in a dose-dependent manner after challenge with the homologous H9N2 virus. Immunohistochemical analyses confirmed the lack of virus replication in the lung and an associated substantial reduction in lung pathology. Dose-dependent protection from severe weight loss was also provided after challenge with the highly virulent mouse-adapted H9N2 virus. Conclusions: The induction of high titers of H9N2-specific HI, virus-neutralizing and NAi antibodies and dose-dependent protection from virus replication and severe disease in animal models suggest that the Vero cell culture-derived whole-virus vaccine will provide an effective intervention in the event of a H9N2 pandemic situation. (C) 2012 Elsevier Ltd. All rights reserved. |
|
ISSN: 0264-410X
|
|
Record 13 of 40
|
|
Herfst, Sander; Schrauwen, Eefje J. A.; Linster,
Martin; Chutinimitkul, Salin; de Wit, Emmie; Munster, Vincent J.; Sorrell,
Erin M.; Bestebroer, Theo M.; Burke, David F.; Smith, Derek J.; Rimmelzwaan,
Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.
|
|
Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
|
|
SCIENCE 336(6088) 1534-1541. JUN 22 2012
|
|
Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and
mortality in humans but thus far has not acquired the ability to be
transmitted by aerosol or respiratory droplet ("airborne
transmission") between humans. To address the concern that the virus
could acquire this ability under natural conditions, we genetically modified
A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in
ferrets. The genetically modified A/H5N1 virus acquired mutations during
passage in ferrets, ultimately becoming airborne transmissible in ferrets.
None of the recipient ferrets died after airborne infection with the mutant
A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding
protein hemagglutinin, and one in the polymerase complex protein basic
polymerase 2, were consistently present in airborne-transmitted viruses. The
transmissible viruses were sensitive to the antiviral drug oseltamivir and
reacted well with antisera raised against H5 influenza vaccine strains. Thus,
avian A/H5N1 influenza viruses can acquire the capacity for airborne
transmission between mammals without recombination in an intermediate host
and therefore constitute a risk for human pandemic influenza.
|
|
ISSN: 0036-8075
|
|
Record 14 of 40
|
|
Hou, Yanxia; Guo, Yingying; Wu, Chunyan; Shen,
Nan; Jiang, Yongping; Wang, Jingfei
|
|
Prediction and Identification of T Cell Epitopes in the H5N1 Influenza
Virus Nucleoprotein in Chicken
|
|
PLOS ONE 7(6). JUN 20 2012
|
|
T cell epitopes can be used for the accurate monitoring of avian
influenza virus (AIV) immune responses and the rational design of vaccines.
No T cell epitopes have been previously identified in the H5N1 AIV virus
nucleoprotein (NP) in chickens. For the first time, this study used homology
modelling techniques to construct three-dimensional structures of the
peptide-binding domains of chicken MHC class I molecules for four commonly
encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was
computationally parsed into octapeptides or nonapeptides according to the
peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes.
Seventy-five peptide sequences were modelled and their MHC class I
molecule-binding abilities were analysed by molecular docking. Twenty-five
peptides (Ten for B4, six for B12, two for B15, and seven for B19) were
predicted to be potential T cell epitopes in chicken. Nine of these peptides
and one unrelated peptide were manually synthesized and their T cell
responses were tested in vitro. Spleen lymphocytes were collected from SPF
chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and
they were stimulated using the synthesized peptides. The secretion of chicken
IFN-gamma and the proliferation of CD8(+) T cells were tested using an ELISA
kit and flow cytometry, respectively. The significant secretion of chicken
IFN-gamma and proliferation of CD8(+) T lymphocytes increased by 13.7% and
11.9% were monitored in cells stimulated with peptides NP89-97 and NP198-206,
respectively. The results indicate that peptides NP89-97 (PKKTGGPIY) and
NP198-206 (KRGINDRNF) are NP T cell epitopes in chicken of certain
haplotypes. The method used in this investigation is applicable to predicting
T cell epitopes for other antigens in chicken, while this study also extends
our understanding of the mechanisms of the immune response to AIV in chicken.
|
|
ISSN: 1932-6203
|
|
Record 15 of 40
|
|
Ehrlich, Hartmut J.; Berezuk, Gregory; Fritsch, Sandor; Aichingere,
Gerald; Singer, Julia; Portsmouth, Daniel; Hart, Mary Kate; El-Amin, Wael;
Kistner, Otfried; Barrett, P. Noel
|
|
Clinical development of a Vero cell culture-derived seasonal influenza
vaccine
|
|
VACCINE 30(29) 4337-4386. JUN 19 2012
|
|
Background: Cell culture technologies have the potential to improve
the robustness and flexibility of influenza vaccine supply and to
substantially shorten manufacturing timelines. We investigated the safety,
immunogenicity and efficacy of a Vero cell culture-derived seasonal influenza
vaccine and utilized these studies to establish a serological correlate of
vaccine protection. Methods: Two multicenter, randomized, double-blind phase
Ill trials were undertaken in the US during the 2008-2009 Northern hemisphere
influenza season, in young (18-49 years) and older (50-64 years and >= 65
years) adult subjects. 7250 young adults were randomized 1:1 to receive
either Vero-derived vaccine or placebo. 3210 older adult subjects were
randomized 8:1 to receive either Vero-derived vaccine or a licensed
egg-derived vaccine. Serum hemagglutination inhibition antibody titers were
assessed 21 days post-vaccination. Vaccine efficacy in preventing cell
culture-confirmed influenza infection was determined for the young adult
population. Local and systemic adverse events were recorded in both studies.
Results: The Vero-derived vaccine was safe and well tolerated in both young and older adults. All US and European immunological licensing thresholds were comfortably met in both populations. Vaccine efficacy in young adults was 79% against A/H1N1 viruses antigenically matching the corresponding vaccine strain and 78.5% for all antigenically matched influenza viruses. A hemagglutination inhibition antibody titer of >= 1:15 provided a reliable correlate of protection for the Vero-derived influenza vaccine, with no additional benefit at titers >1:30. Bridging of the correlate of protection established in the young adult population to the older adult immunogenicity data demonstrated the likely effectiveness of the Vero-derived vaccine in the older adult population. Conclusions: A Vero cell culture-derived seasonal influenza vaccine is safe, immunogenic and protects against infection with influenza virus. The novel vaccine technology has the potential to make a substantial contribution to improving influenza vaccine supply. Clinical trial registration: The studies are registered with ClinicalTrials.gov, numbers NCT00566345 and NCT00782431. (C) 2011 Elsevier Ltd. All rights reserved. |
|
Conference 5th
Semmering Vaccine Symposium APR 28-30, 2011 Baden, AUSTRIA
|
|
ISSN: 0264-410X
|
|
Record 16 of 40
|
|
Rahman, Md Masudur; Uyangaa, Erdenebileg; Han,
Young Woo; Kim, Seong Bum; Kim, Jin Hyoung; Choi, Jin Young; Eo, Seong Kug
|
|
Oral co-administration of live attenuated Salmonella enterica serovar
Typhimurium expressing chicken interferon-alpha and interleukin-18 enhances
the alleviation of clinical signs caused by respiratory infection with avian
influenza virus H9N2
|
|
VETERINARY MICROBIOLOGY 157(3-4) 448-455. JUN 15 2012
|
|
The combined use of cytokines has shown synergistic and/or additive
effects in controlling several viral infections of livestock animals.
However, little is known concerning the practical use of chicken cytokine
combinations to control avian diseases. Here, we investigated the antiviral
efficacy of oral co-administration of chicken interferon-alpha (chIFN-alpha)
and chicken interleukin-18 (chIL-18) using attenuated Salmonella enterica
serovar Typhimurium in chickens infected with avian influenza virus (AIV)
H9N2. Our results demonstrate that oral co-administration of S. enterica
serovar Typhimurium expressing chIFN-alpha and chIL-18 produced a greater
alleviation of clinical signs caused by respiratory infection with AIV H9N2
in chickens, when compared to administration of S. enterica serovar
Typhimurium expressing either chIFN-alpha or chIL-18 alone. Mortality,
clinical symptom severity, and feed and water intake were used to access
treatment effectiveness. This enhancement of antiviral immunity was further
confirmed by evidence of reduced rectal shedding and decreased replication of
AIV H9N2 in several different tissues of challenged chickens including
trachea, lung, cecal tonsil, and brain. Furthermore, oral co-administration
of chIFN-alpha and chIL-18 more efficiently modulated the immune responses of
chickens against AIV H9N2 by enhancing both humoral and Th1-biased
cell-mediated immunity, compared to single administration of either
construct. Therefore, our results suggest that the combined administration of
two chicken cytokines, chIFN-alpha and chIL-18, using attenuated S. enterica
serovar Typhimurium as an oral carrier, provides an effective means for
controlling respiratory disease caused by AIV H9N2 infection. (C)
2011 Elsevier B.V. All rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 17 of 40
|
|
Jing, Xianghong; Phy, Kathryn; Li, Xing; Ye, Zhiping
|
|
Increased hemagglutinin content in a reassortant 2009 pandemic H1N1
influenza virus with chimeric neuraminidase containing donor A/Puerto
Rico/8/34 virus transmembrane and stalk domains
|
|
VACCINE 30(28) 4144-4152. JUN 13 2012
|
|
The glycoproteins, heamagglutinin (HA) and neuraminidase (NA) of
influenza virus confer host protective immune responses during vaccination,
which is the most effective approach for preventing influenza-associated
morbidity and mortality. Since the functional balance between the HA and NA
proteins may affect viral receptor binding and replication, a pandemic
influenza A virus (H1N1 pdm09), strain A/Texas/05/2009, was optimized to
elevate its HA antigen content by modifying the NA gene. In this study, we
have constructed two 2:6 reassortant viruses between pdmH1N1
(A/Texas/05/2009) and A/Puerto Rico/8/34 (PR8), in which the NA gene of
A/Texas/05/2009 was modified to contain part of the NA gene from PR8. One
chimeric NA virus has the PR8 transmembrane (TM) region (HNtm 2:6) and the
other contains both the PR8 NA TM and stem regions (HNst 2:6). Using quantitative
reverse phase-HPLC (RP-HPLC) analysis, we observed that the HNst2:6 virus
contains a higher HA1 content than HN2:6 wild type. In addition, this mutant
virus displays a higher HA1 to nucleoprotein (NP) ratio, based on gel
electrophoresis densitometry analysis. Furthermore, the neuraminidase
activity of purified HNst 2:6 virus is approximately 30% lower than that of
HN2:6 virus, which is suggestive of a lower incorporation of NA into the
viral envelope. Therefore, we propose that the reduction of NA packaging in
the virion may lead to a compensatory increase of HA. Such an improvement in
HA yield is possibly beneficial to H1N1 pdm09 vaccine production. Published
by Elsevier Ltd.
|
|
ISSN: 0264-410X
|
|
Record 18 of 40
|
|
Lin, Shih-Chang; Lin, Yu-Fen; Chong, Pele; Wu, Suh-Chin
|
|
Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost
Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles
|
|
PLOS ONE7(6). JUN 13 2012
|
|
Background: Highly pathogenic avian influenza (HPAI) H5N1 viruses and
their transmission capability from birds to humans have raised global
concerns about a potential human pandemic. The inherent nature of antigenic
changes in influenza viruses has not been sufficiently taken into account in
immunogen designs for broadly protective HPAI H5N1 vaccines. Methods: We
designed a hyperglycosylated HA vaccine using N-linked glycan masking on
highly variable sequences in the HA1 globular head. Immunization of these
hyperglycosylated HA DNA vaccines followed by a flagellin-containing
virus-like particle booster in mice was conducted to evaluate neutralizing
antibody responses against various clades of HPAI H5N1 viruses. Results: We
introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT,
127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence
alignment analyses from 163 HPAI H5N1 human isolates. Although no significant
differences of anti-HA total IgG titers were found with these
hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS
mutants elicited significantly potent cross-clade neutralizing antibodies
against HPAI H5N1 viruses.
Conclusions: This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines. |
|
ISSN: 1932-6203
|
|
Record 19 of 40
|
|
Banner, David; Kelvin, Alyson A.
|
|
The current state of H5N1 vaccines and the use of the ferret model for
influenza therapeutic and prophylactic development
|
|
JOURNAL OF INFECTION IN DEVELOPING COUNTRIES 6(6) 465-469. JUN
2012
|
|
Highly pathogenic avian influenza H5N1 is a threat to global public
health as a natural pandemic causing agent but has recently been considered a
bioterrorism concern. The evolving view of the H5N1 virus necessitates the
re-evaluation of the current status of H5N1 therapeutics and prophylactics,
in particular the preparation of viable H5N1 vaccination strategies as well
as the use of ferrets in influenza research. Here the highly pathogenic H5N1
virus dilemma is discussed in context with the current H5N1 vaccine status
and the use of the ferret model. Previously, the development of various H5N1
vaccine platforms have been attempted, many of them tested in the ferret
model, including vector vaccines, adjuvant vaccines, DNA vaccines, and
reverse engineered vaccines. Moreover, as ferrets are a superlative animal
model for influenza investigation and vaccine testing, it is imperative that
this model is recognized for its uses in prophylactic development and not
only as an agent for creating transmissible influenza viruses. Elucidating
the ferret immune response and creating ferret immune reagents remain
important goals in conjunction with the development and manufacture of H5N1
vaccines. In summary, an efficacious H5N1 vaccine is urgently needed and the
ferret model remains an appropriate model for its development.
|
|
ISSN: 1972-2680
|
|
Record 20 of 40
|
|
Song, Min-Suk; Moon, Ho-Jin; Kwon, Hyeok-il;
Pascua, Philippe Noriel Q.; Lee, Jun Han; Baek, Yun Hee; Woo, Kyu-Jin; Choi,
Juhee; Lee, Sangho; Yoo, Hyunseung; Oh, In Gyeong; Yoon, Yeup; Rho, Jong-Bok;
Sung, Moon-Hee; Hong, Seung-Pyo; Kim, Chul-Joong; Choi, Young Ki
|
|
Evaluation of the Efficacy of a Pre-pandemic H5N1 Vaccine (MG1109) in
Mouse and Ferret Models
|
|
JOURNAL OF MICROBIOLOGY 50(3) 478-488. JUN 2012
|
|
The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus
causing the next pandemic remains a major concern. In this study, we
evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1
pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing
the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1
A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34
(RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice
and ferrets elicited high HI and SN titers in a dose-dependent manner against
the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains,
(RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including
a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient
cross-reactivity was not observed against heterosubtypic H9N2
(A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 mu
g HA/dose of MG1109 were completely protected from lethal challenge with
heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and
mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 mu
g HA/dose efficiently suppressed virus growth in the upper respiratory tract
and lungs. Vaccinated mice and ferrets also demonstrated attenuation of
clinical disease signs and limited virus spread to other organs. Thus, this
vaccine provided immunogenic responses in mouse and ferret models even
against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the
specific strain of HPAI H5N1 virus that would potentially cause the next
outbreak is unknown, pre-pandemic vaccine preparation that could provide
cross-protection against various H5 strains could be a useful approach in the
selection of promising candidate vaccines in the future.
|
|
ISSN: 1225-8873
|
|
Record 21 of 40
|
|
Kim, Yeu-Chun; Song, Jae-Min; Lipatov, Aleksandr
S.; Choi, Seong-O; Lee, Jeong Woo; Donis, Ruben O.; Compans, Richard W.;
Kang, Sang-Moo; Prausnitz, Mark R.
|
|
Increased immunogenicity of avian influenza DNA vaccine delivered to
the skin using a microneedle patch
|
|
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 81(2) 239-247. JUN
2012
|
|
Effective public health responses to an influenza pandemic require an
effective vaccine that can be manufactured and administered to large
populations in the shortest possible time. In this study, we evaluated a
method for vaccination against avian influenza virus that uses a DNA vaccine
for rapid manufacturing and delivered by a microneedle skin patch for
simplified administration and increased immunogenicity. We prepared patches
containing 700-mu m long microneedles coated with an avian H5 influenza
hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The
coating DNA dose increased with DNA concentration in the coating solution and
the number of dip-coating cycles. Coated DNA was released into the skin
tissue by dissolution within minutes. Vaccination of mice using microneedles
induced higher levels of antibody responses and hemagglutination inhibition
titers, and improved protection against lethal infection with avian influenza
as compared to conventional intramuscular delivery of the same dose of the
DNA vaccine. Additional analysis showed that the microneedle coating solution
containing carboxymethylcellulose and a surfactant may have negatively
affected the immunogenicity of the DNA vaccine. Overall, this study shows
that DNA vaccine delivery by microneedles can be a promising approach for
improved vaccination to mitigate an influenza pandemic. (C)
2012 Elsevier B.V. All rights reserved.
|
|
ISSN: 0939-6411
|
|
Record 22 of 40
|
|
Hu, Zhi-peng; Yin, Juan; Zhang, Yuan-yuan; Jia,
Shu-ya; Chen, Zuo-jia; Zhong, Jiang
|
|
Characterization of the immune responses elicited by baculovirus-based
vector vaccines against influenza virus hemagglutinin
|
|
ACTA PHARMACOLOGICA SINICA 33(6) 783-790.
JUN 2012
|
|
Aim: To compare the specific immune responses elicited by different
baculovirus vectors in immunized mice.
Methods: We constructed and characterized two recombinant baculoviruses carrying the expression cassette for the H5N1 influenza virus hemagglutinin (HA) gene driven by either an insect cell promoter (vAc-HA) or a dual-promoter active both in insect and mammalian cells (vAc-HA-DUAL). Virus without the HA gene (vAc-EGFP) was used as a control. These viruses were used to immunize mice subcutaneously and intraperitoneally. The production of total and specific antibodies was determined by ELISA and competitive ELISA. Cytokine production by the spleen cells of immunized mice was studied using the ELISPOT assay. Results: Both the vAc-HA and vAc-HA-DUAL vectors expressed HA proteins in insect Sf9 cells, and HA antigen was present in progeny virions. The vAc-HA-DUAL vector also mediated HA expression in virus-transduced mammalian cell lines (BHK and A547). Both vAcHA and vAc-HA-DUAL exhibited higher transduction efficiencies than vAc-EGFP in mammalian cells, as shown by the expression of the reporter gene egfp. Additionally, both vAc-HA and vAc-HA-DUAL induced high levels of HA-specific antibody production in immunized mice; vAc-HA-DUAL was more efficient in inducing IFN-gamma and IL-2 upon stimulation with specific antigen, whereas vAc-HA was more efficient in inducing IL-4 and IL-6. Conclusion: Baculovirus vectors elicited efficient, specific immune responses in immunized mice. The vector displaying the HA antigen on the virion surface (vAc-HA) elicited a Th2-biased immune response, whereas the vector displaying HA and mediating HA expression in the cell (vAc-HA-DUAL) elicited a Th1-biased immune response. |
|
ISSN: 1671-4083
|
|
Record 23 of 40
|
|
Ngunjiri, John M.; Lee, Chang-Won; Ali, Ahmed; Marcus, Philip I.
|
|
Influenza Virus Interferon-Inducing Particle Efficiency Is Reversed in
Avian and Mammalian Cells, and Enhanced in Cells Co-Infected with Defective-Interfering
Particles
|
|
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 32(6) 280-285. JUN 2012
|
|
Naturally selected variants of influenza virus encoding truncated NS1
proteins were tested in chickens as candidate live-attenuated influenza
vaccines. Their effectiveness correlated with the amount of interferon (IFN)
induced in chicken cells. Effective variants induced large amounts of IFN and
contained subpopulations with high ratios of defective-interfering particles:
IFN-inducing particles (DIP: IFP). Ineffective variants induced less IFN and
contained lower ratios of DIP: IFP. Unexpectedly, there was a reversal of
phenotypes in mammalian cells. Variants that induced low amounts of IFN and
had low DIP: IFP ratios in chicken cells were excellent IFN inducers with high
DIP: IFP ratios in mammalian cells, and vice versa. The high DIP: IFP ratios
and computer-simulated dynamics of infection suggested that DIP, as an
individual particle, did not function as an IFP. The higher efficiency of
IFPs in the presence of DIPs was attributed to reduced amounts of newly
synthesized viral polymerase known to result from out-competition by
defective-interfering RNAs, and the subsequent failure of that polymerase to
turn-off cellular mRNA transcription-including IFN-mRNA.
|
|
ISSN: 1079-9907
|
|
Record 24 of 40
|
|
Zhou, Fan; Wang, Guiqin; Buchy, Philippe; Cai,
Zhipeng; Chen, Honglin; Chen, Zhiwei; Cheng, Genhong; Wan, Xiu-Feng; Deubel,
Vincent; Zhou, Paul
|
|
A Triclade DNA Vaccine Designed on the Basis of a Comprehensive
Serologic Study Elicits Neutralizing Antibody Responses against All Clades
and Subclades of Highly Pathogenic Avian Influenza H5N1 Viruses
|
|
JOURNAL OF VIROLOGY86(12) 6970-6978. JUN
2012
|
|
Because of their rapid evolution, genetic diversity, broad host range,
ongoing circulation in birds, and potential human-to-human transmission, H5N1
influenza viruses remain a major global health concern. Their high degree of
genetic diversity also poses enormous burdens and uncertainties in developing
effective vaccines. To overcome this, we took a new approach, i.e., the
development of immunogens based on a comprehensive serologic study. We
constructed DNA plasmids encoding codon-optimized hemagglutinin (HA) from 17
representative strains covering all reported clades and subclades of highly pathogenic
avian influenza H5N1 viruses. Using DNA plasmids, we generated the
corresponding H5N1 pseudotypes and immune sera. We performed an
across-the-board pseudotype-based neutralization assay and determined
antigenic clusters by cartography. We then designed a triclade DNA vaccine
and evaluated its immunogenicity and protection in mice. We report here that
(sub)clades 0, 1, 3, 4, 5, 6, 7.1, and 9 were grouped into antigenic cluster
1, (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5, and 8 were grouped into another antigenic
cluster, with subclade 2.2.1 loosely connected to it, and each of subclades
2.3.2.1 and 7.2 was by itself. Importantly, the triclade DNA vaccine encoding
HAs of (sub)clades 0, 2.3.2.1, and 7.2 elicited broadly neutralizing antibody
responses against all H5 clades and subclades and protected mice against
high-lethal-dose heterologous H5N1 challenge. Thus, we conclude that broadly
neutralizing antibodies against all H5 clades and subclades can indeed be
elicited with immunogens on the basis of a comprehensive serologic study.
Further evaluation and optimization of such an approach in ferrets and in
humans is warranted.
|
|
ISSN: 0022-538X
|
|
Record 25 of 40
|
|
Woodland, David L.
|
|
Cutting-Edge Articles on the Host Response to Viral Infections
|
|
VIRAL IMMUNOLOGY 25(3) 173-173.
JUN 2012
|
|
ISSN:
0882-8245
|
|
Record 26 of 40
|
|
Mallick, Amirul I.; Kulkarni, Raveendra R.; St Paul, Michael; Parvizi,
Payvand; Nagy, Eva; Behboudi, Shahriar; Sharif, Shayan
|
|
Vaccination with CpG-Adjuvanted Avian Influenza Virosomes Promotes
Antiviral Immune Responses and Reduces Virus Shedding in Chickens
|
|
VIRAL IMMUNOLOGY 25(3) 226-231.
JUN 2012
|
|
The use of virosomes as a vaccine platform has proven successful
against several viruses. Here we examined the protective efficacy of a
virosome-based vaccine consisting of avian influenza virus (AIV)
A/Duck/Czech/56/H4N6 in chickens against a homologous AIV challenge.
Virosomes adjuvanted with CpG-ODN or recombinant chicken interferon
(IFN)-gamma significantly reduced virus shedding after virus challenge.
Furthermore, immunization with virosomes adjuvanted with CpG-ODN increased
hemagglutination inhibition (HI) and virus-specific neutralizing serum
antibodies, as well as virus-specific serum IgG and mucosal IgA responses. We
also found a significant increase in the expression of type I and II
interferon genes in the protected birds following virus challenge. In
summary, this study demonstrated the ability of virosomes adjuvanted with
CpG-ODN to reduce AIV shedding, and elicit virus-specific protective antibody
responses in vaccinated birds.
|
|
ISSN: 0882-8245
|
|
Record 27 of 40
|
|
Tan, Gene S.; Krammer, Florian; Eggink, Dirk; Kongchanagul, Alita;
Moran, Thomas M.; Palese, Peter
|
|
A Pan-H1 Anti-Hemagglutinin Monoclonal Antibody with Potent
Broad-Spectrum Efficacy In Vivo
|
|
JOURNAL OF VIROLOGY 86(11) 6179-6188. JUN
2012
|
|
Seasonal epidemics caused by antigenic variations in influenza A virus
remain a public health concern and an economic burden. The isolation and
characterization of broadly neutralizing anti-hemagglutinin monoclonal
antibodies (MAb) have highlighted the presence of highly conserved epitopes
in divergent influenza A viruses. Here, we describe the generation and
characterization of a mouse monoclonal antibody designed to target the
conserved regions of the hemagglutinin of influenza A H1 viruses, a subtype
that has caused pandemics in the human population in both the 20th and 21st
centuries. By sequentially immunizing mice with plasmid DNA encoding the
hemagglutinin of antigenically different HI influenza A viruses (A/South
Carolina/1/1918, A/USSR/92/1977, and A/California/4/2009), we isolated and
identified MAb 6F12. Similar to other broadly neutralizing MAb previously
described, MAb 6F12 has no hemagglutination inhibition activity against influenza
A viruses and targets the stalk region of hemagglutinins. As designed, it has
neutralizing activity against a divergent panel of H1 viruses in vitro,
representing 79 years of antigenic drift. Most notably, MAb 6F12 prevented
gross weight loss against divergent H1 viruses in passive transfer
experiments in mice, both in pre- and postexposure prophylaxis regimens. The
broad but specific activity of MAb 6F12 highlights the potent efficacy of
monoclonal antibodies directed against a single subtype of influenza A virus.
|
|
ISSN: 0022-538X
|
|
Record 28 of 40
|
|
Liu, Kun; Yao, Zhidong; Zhang, Liangyan; Li,
Junli; Xing, Li; Wang, Xiliang
|
|
MDCK cell-cultured influenza virus vaccine protects mice from lethal
challenge with different influenza viruses
|
|
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY 94(5) 1173-1179. JUN 2012
|
|
Influenza epidemics are major health concern worldwide. Vaccination is
the major strategy to protect the general population from a pandemic.
Currently, most influenza vaccines are manufactured using chicken embroynated
eggs, but this manufacturing method has potential limitations, and cell-based
vaccines offer a number of advantages over the traditional method. We
reported here using the scalable bioreactor to produce pandemic influenza
virus vaccine in a Madin-Darby canine kidney cell culture system. In the
7.5-L bioreactor, the cell concentration reached to 3.2 x 10(6) cells/mL and
the highest virus titers of 256 HAU/50 mu L and 1 x 10(7) TCID50/mL. The HA
concentration was found to be 11.2 mu g/mL. The vaccines produced by the
cell-cultured system induced neutralization antibodies, cross-reactive T-cell
responses, and were protective in a mouse model against different lethal
influenza virus challenge. These data indicate that microcarrier-based
cell-cultured influenza virus vaccine manufacture system in scalable
bioreactor could be used to produce effective pandemic influenza virus
vaccines.
|
|
ISSN: 0175-7598
|
|
Record 29 of 40
|
|
Cao, Zhiliang; Meng, Jiazi; Li, Xingxing; Wu,
Ruiping; Huang, Yanxin; He, Yuxian
|
|
The Epitope and Neutralization Mechanism of AVFluIgG01, a
Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus
|
|
PLOS ONE 7(5). MAY 25 2012
|
|
The continued spread of highly pathogenic avian influenza (HPAI) H5N1
virus underscores the importance of effective antiviral approaches.
AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal
antibody (mAb) showing great potential for use either for therapeutic
purposes or as a basis of vaccine development, but its antigenic epitope and
neutralization mechanism have not been finely characterized. In this study,
we first demonstrated that AVFluIgG01 targets a novel conformation-dependent
epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting
mimotopes from a random peptide library in combination with computational
algorithms and site-directed mutagenesis, the epitope was mapped to three
conserved discontinuous sites (I-III) that are located closely at the
three-dimensional structure of HA. Further, we found that this HA1-specific
human mAb can efficiently block both virus-receptor binding and
post-attachment steps, while its Fab fragment exerts the post-attachment
inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell
membrane fusion at a dose-dependent manner and block the acquisition of
pH-induced protease sensitivity. These results suggest a neutralization
mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the
receptors on host cells and interfering with HA conformational rearrangements
associated with membrane fusion. The presented data provide critical
information for developing novel antiviral therapeutics and vaccines against
HPAI H5N1 virus.
|
|
ISSN: 1932-6203
|
|
Record 30 of 40
|
|
Chaung, Hso-Chi; Cheng, Li-Ting; Hung, Li-Hsiang;
Tsai, Pei-Chun; Skountzou, Ioanna; Wang, Baozhong; Compans, Richard W.; Lien,
Yi-Yang
|
|
Salmonella flagellin enhances mucosal immunity of avian influenza
vaccine in chickens
|
|
VETERINARY MICROBIOLOGY 157(1-2) 69-77. MAY 25 2012
|
|
Flagellin, a bioactive Toll-like receptor (TLR) 5 ligand, may trigger
the innate immunity that in turn is important for subsequent adaptive immune
responses. In the present study, the adjuvant effects of the monomeric and
polymeric forms of Salmonella flagellin (mFliC and pFliC, respectively) were
examined in specific-pathogen free (SPF) chickens immunized intramuscularly
(i.m.) or intranasally (i.n.) with formalin-inactivated avian influenza virus
(AIV) H5N2 vaccines. Results showed that mFliC cooperating with the 64CpG
adjuvant significantly induced influenza-specific antibody titers of plasma
IgA in the i.m.-vaccinated animals. The nasal IgA levels in the
i.n.-mFliC-coadministrated AIV vaccinated chickens were significantly
elevated compared to levels observed in the control group (H5N2 vaccine
alone). The pFliC cooperating with the 64CpG adjuvant significantly enhanced
cell proliferation of splenocytes in the i.m.-vaccinated animals. TLR3 and
TLR5 expressions were activated by flagellin stimulation in vitro and in vivo.
These results suggest that flagellin can be used as an adjuvant in an AIV
H5N2 vaccine, especially for mucosal immunity. (C) 2011 Elsevier B.V. All
rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 31 of 40
|
|
Arikata, Masahiko; Itoh, Yasushi; Okamatsu,
Masatoshi; Maeda, Toshinaga; Shiina, Takashi; Tanaka, Keiko; Suzuki, Shingo;
Nakayama, Misako; Sakoda, Yoshihiro; Ishigaki, Hirohito; Takada, Ayato;
Ishida, Hideaki; Soda, Kosuke; Van Loi Pham; Tsuchiya, Hideaki; Nakamura,
Shinichiro; Torii, Ryuzo; Shimizu, Takeshi; Inoko, Hidetoshi; Ohkubo, Iwao;
Kida, Hiroshi; Ogasawara, Kazumasa
|
|
Memory Immune Responses against Pandemic (H1N1) 2009 Influenza Virus
Induced by a Whole Particle Vaccine in Cynomolgus Monkeys Carrying
Mafa-A1*052:02
|
|
PLOS ONE 7(5). MAY 18 2012
|
|
We made an H1N1 vaccine candidate from a virus library consisting of
144 (= 16 HAx9 NA) non-pathogenic influenza A viruses and examined its
protective effects against a pandemic (2009) H1N1 strain using
immunologically naive cynomolgus macaques to exclude preexisting immunity and
to employ a preclinical study since preexisting immunity in humans previously
vaccinated or infected with influenza virus might make comparison of vaccine
efficacy difficult. Furthermore, macaques carrying a major histocompatibility
complex class I molecule, Mafa-A1*052:02, were used to analyze
peptide-specific CD8(+) T cell responses. Sera of macaques immunized with an
inactivated whole particle formulation without addition of an adjuvant showed
higher neutralization titers against the vaccine strain A/Hokkaido/2/1981
(H1N1) than did sera of macaques immunized with a split formulation.
Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1)
in sera of macaques immunized twice with the split vaccine reached levels similar
to those in sera of macaques immunized once with the whole particle vaccine.
After inoculation with the pandemic virus, the virus was detected in nasal
samples of unvaccinated macaques for 6 days after infection and for 2.67 days
and 5.33 days on average in macaques vaccinated with the whole particle
vaccine and the split vaccine, respectively. After the challenge infection,
recall neutralizing antibody responses against the pandemic virus and CD8(+)
T cell responses specific for nucleoprotein peptide NP262-270 bound to
Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were
observed more promptly or more vigorously than those in macaques vaccinated
with the split vaccine. These findings demonstrated that the vaccine derived
from our virus library was effective for pandemic virus infection in macaques
and that the whole particle vaccine conferred more effective memory and
broader cross-reactive immune responses to macaques against pandemic
influenza virus infection than did the split vaccine.
|
|
ISSN: 1932-6203
|
|
Record 32 of 40
|
|
Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui;
Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang
|
|
High-yield production of a stable Vero cell-based vaccine candidate
against the highly pathogenic avian influenza virus H5N1
|
|
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 421(4) 850-854.
MAY 18 2012
|
|
Highly pathogenic avian influenza (HPAI) viruses pose a global
pandemic threat, for which rapid large-scale vaccine production technology is
critical for prevention and control. Because chickens are highly susceptible
to HPAI viruses, the supply of chicken embryos for vaccine production might
be depleted during a virus outbreak. Therefore, developing HPAI virus
vaccines using other technologies is critical. Meeting vaccine demand using
the Vero cell-based fermentation process has been hindered by low stability
and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate
(H5N1/YNVa) with stable high yield was achieved by reassortment of the
Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the
A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using
the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high
hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low
pathogenicity and uniform immunogenicity compared to that of the parent
virus. (C)
2012 Elsevier Inc. All rights reserved.
|
|
ISSN: 0006-291X
|
|
Record 33 of 40
|
|
Giles, Brendan M.; Crevar, Corey J.; Carter, Donald M.; Bissel,
Stephanie J.; Schultz-Cherry, Stacey; Wiley, Clayton A.; Ross, Ted M.
|
|
A Computationally Optimized Hemagglutinin Virus-Like Particle Vaccine
Elicits Broadly Reactive Antibodies that Protect Nonhuman Primates from H5N1
Infection
|
|
JOURNAL OF INFECTIOUS DISEASES 205(10)1562-1570. MAY 15 2012
|
|
Highly pathogenic H5N1 avian influenza viruses continue to spread via
waterfowl, causing lethal infections in humans. Vaccines can prevent the
morbidity and mortality associated with pandemic influenza isolates. Predicting
the specific isolate that may emerge from the 10 different H5N1 clades is a
tremendous challenge for vaccine design.
In this study, we generated a synthetic hemagglutinin (HA) on the basis of a new method, computationally optimized broadly reactive antigen (COBRA), which uses worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates. Cynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLPs) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades as compared to nonhuman primates vaccinated with clade 2.2 HA VLPs. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge, with no virus detected in the nasal or tracheal washes. However, COBRA VLP-vaccinated nonhuman primates had reduced lung inflammation and pathologic effects as compared to those that received WS/05 VLP vaccines. The COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine is more effective than a homologous vaccine against a highly pathogenic avian influenza virus challenge. |
|
ISSN: 0022-1899
|
|
Record 34 of 40
|
|
Meliopoulos, Victoria A.; Andersen, Lauren E.; Brooks, Paula; Yan,
Xiuzhen; Bakre, Abhijeet; Coleman, J. Keegan; Tompkins, S. Mark; Tripp, Ralph
A.
|
|
MicroRNA Regulation of Human Protease Genes Essential for Influenza
Virus Replication
|
|
PLOS ONE 7(5) MAY 14 2012
|
|
Influenza A virus causes seasonal epidemics and periodic pandemics
threatening the health of millions of people each year. Vaccination is an
effective strategy for reducing morbidity and mortality, and in the absence
of drug resistance, the efficacy of chemoprophylaxis is comparable to that of
vaccines. However, the rapid emergence of drug resistance has emphasized the
need for new drug targets. Knowledge of the host cell components required for
influenza replication has been an area targeted for disease intervention. In
this study, the human protease genes required for influenza virus replication
were determined and validated using RNA interference approaches. The genes
validated as critical for influenza virus replication were ADAMTS7, CPE,
DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in
global host cell pathways governing inflammation (NF-kappa B), cAMP/calcium
signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to
govern expression of these genes showed that eight miRNAs regulated gene
expression during virus replication. These findings identify unique host
genes and microRNAs important for influenza replication providing potential
new targets for disease intervention strategies.
|
|
ISSN: 1932-6203
|
|
Record 35 of 40
|
|
Schmeisser, Falko; Adamo, Joan E.; Blumberg, Benjamin; Friedman,
Rachel; Muller, Jacqueline; Soto, Jackeline; Weir, Jerry P.
|
|
Production and characterization of mammalian virus-like particles from
modified vaccinia virus Ankara vectors expressing influenza H5N1
hemagglutinin and neuraminidase
|
|
VACCINE 30(23) 3413-3422. MAY 14
2012
|
|
Several studies have described the production of influenza virus-like
particles (VLP) using a variety of platform systems. These VLPs are
non-replicating particles that spontaneously self-assemble from expressed
influenza virus proteins and have been proposed as vaccine candidates for
both seasonal and pandemic influenza. Although still in the early stages of
development and evaluation as influenza vaccines, influenza VLPs have a
variety of other valuable uses such as examining and understanding correlates
of protection against influenza and investigating virus-cell interactions.
The most common production system for influenza VLPs is the
baculovirus-insect cell expression which has several attractive features
including the ease in which new gene combinations can be constructed, the
immunogenicity elicited and protection afforded by the produced VLPs, and the
scalability offered by the system. However, there are differences between the
influenza VLPs produced by baculovirus expression systems in insect cells and
the influenza viruses produced for use as current vaccines or the virus
produced during a productive clinical infection. We describe here the
development of a modified vaccinia virus Ankara (MVA) system to generate
mammalian influenza VLPs containing influenza H5N1 proteins. The MVA vector
system is flexible for manipulating and generating various VLP constructs,
expresses high level of influenza hemagglutinin (HA), neuraminidase (NA), and
matrix (M) proteins, and can be scaled up to produce VLPs in quantities
sufficient for in vivo studies. We show that mammalian VLPs are generated
from recombinant MVA vectors expressing H5N1 HA alone, but that increased VLP
production can be achieved if NA is co-expressed. These mammalian H5N1
influenza VLPs have properties in common with live virus, as shown by
electron microscopy analysis, their ability to hemagglutinate red blood
cells, express neuraminidase activity, and to bind influenza specific
antibodies. Importantly, these VLPs are able to elicit a protective immune
response in a mouse challenge model, suggesting their utility in dissecting
the correlates of immunity in such models. Mammalian derived VLPs may also
provide a useful tool for studying virus-cell interactions and may have
potential for development as pandemic vaccines. Published by Elsevier Ltd.
|
|
ISSN: 0264-410X
|
|
Record 36 of 40
|
|
Read, A. J.; Arzey, K. E.; Finlaison, D. S.; Gu, X.; Davis, R. J.;
Ritchie, L.; Kirkland, P. D.
|
|
A prospective longitudinal study of naturally infected horses to
evaluate the performance characteristics of rapid diagnostic tests for equine
influenza virus
|
|
VETERINARY MICROBIOLOGY
156(3-4) 246-255. MAY 4 2012
|
|
An outbreak of equine influenza (EI) occurred in Australia in 2007.
During the laboratory support for this outbreak, real-time reverse
transcriptase polymerase chain reaction (qRT-PCR) assays and a blocking
enzyme linked immunosorbent assay (bELISA) were used as testing methods to
detect infection with the virus. The qRT-PCR and bELISA tests had not been
used for El diagnosis before, so it was not known how soon after infection
these tests would yield positive results, or for how long these results would
remain positive. To answer these questions, nasal swabs and blood samples
were collected daily from a group of 36 naturally infected horses. El viral
RNA was detected in all horses by qRT-PCR from the first to tenth day after
clinical signs were evident, and was detected in some horses for up to 34
days. Antibody was detected in the bELISA in some horses by day 3, with a
median time to seroconversion of 5 days. The results from this study indicate
that viral RNA can be detected from nasal swabs for much longer than
infectious virus is thought to be shed from horses. The bELISA detected
antibodies against El virus in all horses for 139 days following infection,
but only detected approximately 50% of horses 12 months following infection.
Haemagglutination inhibition testing detected antibodies against H3 antigens
in all horses for 28 days following infection, but 2 were negative by 35 days
following infection. Crown Copyright (C) 2011 Published by Elsevier B.V. All
rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 37 of 40
|
|
Desvaux, S.; Garcia, J. M.; Nguyen, T. D.; Reid,
S. A.; Bui, N. A.; Roger, F.; Fenwick, S.; Peiris, J. S. M.; Ellis, T.
|
|
Evaluation of serological tests for H5N1 avian influenza on field
samples from domestic poultry populations in Vietnam: Consequences for
surveillance
|
|
VETERINARY MICROBIOLOGY
156(3-4) 277-284. MAY 4 2012
|
|
In Vietnam, serological post H5N1 vaccination surveillance using the
HI test is applied to assess the efficiency of the vaccination in addition to
virological monitoring. In this paper we report on the evaluations of the
performances of the haemagglutination inhibition (HI) test and of a H5-ELISA,
using chicken and duck field samples. The evaluations were conducted by
comparison with a pseudotyped-based virus neutralization test (H5pp VNT)
performed in a reference laboratory and considered as a "gold
standard" and also by using methods developed for imperfect reference
test. Their global accuracy and best cut-offs were also estimated. Results
from the HI test for several haemagglutinin subtypes and from a commercial
type A influenza competition ELISA were also compared. The results showed
that performance of the HI test was very good in comparison with the H5pp
VNT. Data also clearly supported the cut-off of >4 log, used for the HI
test for chickens but, a 3 log(2) positivity cut-off would be more
appropriate for ducks. When compared with the VNT, the H5-ELISA showed poor
specificity when using the positivity cut-off specified by the manufacturer
but could be used as a screening test if confirmed by the HI test or the
H5ppVNT which presents some interests for large scale testing (no need for
biosafety level 3 conditions and high performance). A general and highly
sensitive pre-screening can also be achieved using the detection of
NP-specific antibodies with a competition ELISA. This appears of little
interest in a context of high subtypes diversity where only a subtype is
targeted for surveillance and control. (C) 2011 Elseviel B.V. All
rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 38 of 40
|
|
Zhang, Yi; Yin, Yanbo; Bi, Yuhai; Wang, Shouchun;
Xu, Shouzhen; Wang, Jianlin; Zhou, Shun; Sun, Tingting; Yoon, Kyoung-Jin
|
|
Molecular and antigenic characterization of H9N2 avian influenza virus
isolates from chicken flocks between 1998 and 2007 in China
|
|
VETERINARY MICROBIOLOGY
156(3-4) 285-293. MAY 4 2012
|
|
Despite extensive vaccination, H9N2 subtype influenza A viruses have
prevailed in chicken populations in China. H9N2 IAVs have been a major cause
of respiratory disease and reduced egg production, resulting in great
economic losses to the Chinese poultry industry. In attempt to find reasons
for lack of adequate protection by commercial vaccines, 41 H9N2 viruses
isolated from chicken flocks in various regions of China through surveillance
between 1998 and 2007 were systemically analyzed using molecular and
serological methods in comparison to IAV Ck/Shandong/6/96 and
Ck/Shanghai/F/98 that have been used in a majority of commercial vaccines for
H9N2 in China since 1998. The analyses showed that the field isolates were
predominantly of Beijing/94 lineage and underwent rapid genetic and antigenic
changes, forming several antigenic groups. Comparisons between the field
isolates and vaccine strains revealed that a majority of the field isolates examined
were antigenically distinct from the vaccine strains to some extent.
Therefore, the rapid antigenic evolution of H9N2 IAV and resulting antigenic
difference from the earlier vaccine strains appears to be a key factor for
sub optimal control of H9N2 IAV in China, emphasizing that the vaccine strain
should be updated in a timely manner through surveillance and accompanying
laboratory evaluation of contemporary viruses for antigenic similarity with
existing vaccine strains. (C) 2011 Elsevier B.V. All rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 39 of 40
|
|
Bi-Hung, Peng; Nadezhda, Yun; Olga, Chumakova;
Michele, Zacks; Gerald, Campbell; Jeanon, Smith; Jennifer, Smith; Seth,
Linde; Jenna, Linde; Slobodan, Paessler
|
|
Neuropathology of H5N1 virus infection in ferrets
|
|
VETERINARY MICROBIOLOGY
156(3-4) 294-304. MAY 4 2012
|
|
Highly pathogenic H5N1 virus remains a potential threat to humans.
Over 289 fatalities have been reported in WHO confirmed human cases since
2003, and lack of effective vaccines and early treatments contribute to
increasing numbers of cases and fatalities. H5N1 encephalitis is a recognized
cause of death in Vietnamese cases, and brain pathology is described in other
human cases and naturally infected animals. However, neither pathogenesis of
H5N1 viral infection in human brain nor post-infection effects in survivors
have been fully investigated. We report the brain pathology in a ferret model
for active infection and 18-day survival stages. This model closely resembles
the infection pattern and progression in human cases of influenza A, and our
report is the first description of brain pathology for longer term (18-day)
survival in ferrets. We analyzed viral replication, type and severity of
meningoencephalitis, infected cell types, and cellular responses to
infection. We found viral replication to very high titers in ferret brain,
closely correlating with severity of meningoencephalitis. Viral antigens were
detected predominantly in neurons, correlating with inflammatory lesions, and
less frequently in astrocytes and ependymal cells during active infection.
Mononuclear cell infiltrates were observed in early stages predominantly in
cerebral cortex, brainstem, and leptomeninges, and less commonly in
cerebellum and other areas. Astrogliosis was mild at day 4 post-infection,
but robust by day 18. Early and continuous treatment with an antiviral agent
(peramivir) inhibited virus production to non-detectable levels, reduced
severity of brain injury, and promoted higher survival rates. (C)
2011 Elsevier B.V. All rights reserved.
|
|
ISSN: 0378-1135
|
|
Record 40 of 40
|
|
Montomoli, Emanuele; Khadang, Baharak;
Piccirella, Simona; Trombetta, Claudia; Mennitto, Elisa; Manini, Ilaria;
Stanzani, Valerio; Lapini, Giulia
|
|
Cell culture-derived influenza vaccines from Vero cells: a new horizon
for vaccine production
|
|
EXPERT REVIEW OF VACCINES 11(5) 587-594. MAY 2012
|
|
In the 20th century, three influenza pandemics killed approximately
100 million people. The traditional method of influenza vaccine manufacturing
is based on using chicken eggs. However, the necessity of the availability of
millions of fertile eggs in the event of a pandemic has led research to focus
on the development of cell culture-derived vaccines, which offer shorter
lead-in times and greater flexibility of production. So far, the cell
substrates being evaluated and in use include Vero, Madin-Darby canine
kidney, PER. C6 and insect cells. However, Vero cells are the most widely
accepted among others. This review introduces briefly the concepts of
advanced cell culture-derived influenza vaccine production and highlights the
advantages of these vaccines in terms of efficiency, speed and immunogenicity
based on the clinical data obtained from different studies.
|
|
ISSN: 1476-0584
|
No hay comentarios:
Publicar un comentario