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Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.
PLoS Pathog. 2009 May; 5(5):e1000409.PP

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.

Authors+Show Affiliations

Animal Influenza Laboratory of the Ministry of Agriculture and National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19412338

Citation

Fan, Shufang, et al. "Immunogenicity and Protective Efficacy of a Live Attenuated H5N1 Vaccine in Nonhuman Primates." PLoS Pathogens, vol. 5, no. 5, 2009, pp. e1000409.
Fan S, Gao Y, Shinya K, et al. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathog. 2009;5(5):e1000409.
Fan, S., Gao, Y., Shinya, K., Li, C. K., Li, Y., Shi, J., Jiang, Y., Suo, Y., Tong, T., Zhong, G., Song, J., Zhang, Y., Tian, G., Guan, Y., Xu, X. N., Bu, Z., Kawaoka, Y., & Chen, H. (2009). Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathogens, 5(5), e1000409. https://doi.org/10.1371/journal.ppat.1000409
Fan S, et al. Immunogenicity and Protective Efficacy of a Live Attenuated H5N1 Vaccine in Nonhuman Primates. PLoS Pathog. 2009;5(5):e1000409. PubMed PMID: 19412338.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. AU - Fan,Shufang, AU - Gao,Yuwei, AU - Shinya,Kyoko, AU - Li,Chris Kafai, AU - Li,Yanbing, AU - Shi,Jianzhong, AU - Jiang,Yongping, AU - Suo,Yongbing, AU - Tong,Tiegang, AU - Zhong,Gongxun, AU - Song,Jiasheng, AU - Zhang,Ying, AU - Tian,Guobin, AU - Guan,Yuntao, AU - Xu,Xiao-Ning, AU - Bu,Zhigao, AU - Kawaoka,Yoshihiro, AU - Chen,Hualan, Y1 - 2009/05/01/ PY - 2008/09/18/received PY - 2009/04/01/accepted PY - 2009/5/5/entrez PY - 2009/5/5/pubmed PY - 2009/8/27/medline SP - e1000409 EP - e1000409 JF - PLoS pathogens JO - PLoS Pathog VL - 5 IS - 5 N2 - 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. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/19412338/Immunogenicity_and_protective_efficacy_of_a_live_attenuated_H5N1_vaccine_in_nonhuman_primates_ L2 - https://dx.plos.org/10.1371/journal.ppat.1000409 DB - PRIME DP - Unbound Medicine ER -