Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.
Identifieur interne : 000236 ( PubMed/Corpus ); précédent : 000235; suivant : 000237Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.
Auteurs : Shufang Fan ; Yuwei Gao ; Kyoko Shinya ; Chris Kafai Li ; Yanbing Li ; Jianzhong Shi ; Yongping Jiang ; Yongbing Suo ; Tiegang Tong ; Gongxun Zhong ; Jiasheng Song ; Ying Zhang ; Guobin Tian ; Yuntao Guan ; Xiao-Ning Xu ; Zhigao Bu ; Yoshihiro Kawaoka ; Hualan ChenSource :
- PLoS pathogens [ 1553-7374 ] ; 2009.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Antibodies, Viral (blood), Body Temperature, Female, Influenza A Virus, H5N1 Subtype (immunology), Influenza A Virus, H5N1 Subtype (physiology), Influenza Vaccines (immunology), Injections, Intravenous, Macaca mulatta, Mice, Mice, Inbred BALB C, Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (virology), Reassortant Viruses (immunology), T-Lymphocytes (immunology), Vaccination, Vaccines, Attenuated (immunology), Viral Load, Virus Replication, Virus Shedding.
- MESH :
- chemical , blood : Antibodies, Viral.
- immunology : Influenza A Virus, H5N1 Subtype, Influenza Vaccines, Reassortant Viruses, T-Lymphocytes, Vaccines, Attenuated.
- physiology : Influenza A Virus, H5N1 Subtype.
- prevention & control : Orthomyxoviridae Infections.
- virology : Orthomyxoviridae Infections.
- Administration, Intranasal, Animals, Body Temperature, Female, Injections, Intravenous, Macaca mulatta, Mice, Mice, Inbred BALB C, Vaccination, Viral Load, Virus Replication, Virus Shedding.
Abstract
The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N1 virus A/VN/1203/2004 (clade 1) was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca) that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05) (clade 2.3), and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca). AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2). These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.
DOI: 10.1371/journal.ppat.1000409
PubMed: 19412338
Links to Exploration step
pubmed:19412338Le document en format XML
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<front><div type="abstract" xml:lang="en">The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N1 virus A/VN/1203/2004 (clade 1) was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca) that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05) (clade 2.3), and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca). AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2). These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.</div>
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