Skip to main content
Article thumbnail
Location of Repository

Immunogenicity and Protective Efficacy of a Live Attenuated H5N1 Vaccine in Nonhuman Primates

By 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 and Hualan Chen

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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2669169
Provided by: PubMed Central

Suggested articles

Citations

  1. (2000). A DNA transfection system for generation of influenza A virus from eight plasmids.
  2. (2005). Avian flu: isolation of drug-resistant H5N1 virus.
  3. (1998). Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.
  4. (1998). Characterization of avian H5N1influenzavirusesfrom poultryin HongKong. Virology 252:331–342.
  5. ChenH,DengG,LiZ,TianG,LiY,etal.(2004)TheevolutionofH5N1influenza viruses in ducks in southern China.
  6. (1985). Development and characterization of coldadapted viruses for use as live virus vaccines.
  7. (2006). Distribution of amantadine-resistant H5N1 avian influenza variants in Asia.
  8. (2003). Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics.
  9. (2003). Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate.
  10. (1999). Generation of influenza A viruses entirely from cloned cDNAs.
  11. (2008). Human infection with highly pathogenic H5N1 influenza virus.
  12. (2007). Human influenza A (H5N1) cases, urban areas of People’s Republic of China,
  13. (1998). Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus.
  14. (1988). Identification of sequence changes in the cold-adapted, live attenuated influenza vaccine strain, A/Ann
  15. (2007). Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus.
  16. (2005). Influenza A H5N1 replication sites in humans.
  17. (2006). Lethal avian influenza A (H5N1) infection in a pregnant woman in Anhui Province,
  18. (2007). Live Attenuated versus Inactivated Influenza Vaccine in Infants and Young Children.
  19. (2006). Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.
  20. (2005). Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model.
  21. (2005). Oseltamivir resistance during treatment of influenza A (H5N1) infection.
  22. (2002). Principles underlying the development and use of live attenuated cold-adapted influenza A and B virus vaccines.
  23. (2006). Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China.
  24. (1999). Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses.
  25. (1999). Rescue of influenza A virus from recombinant DNA.
  26. (2006). Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial.
  27. (2006). Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial.
  28. (2006). Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine.
  29. (2007). Scientific barriers to developing vaccines against avian influenza viruses.
  30. (2008). Update on avian influenza A (H5N1) virus infection in humans.
  31. (2008). Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus (H5N1) Live Vaccine for H5N1

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.