Immunogenicity and protective efficacy of a live attenuated vaccine against the 2009 pandemic A H1N1 in mice and ferrets.
A novel 2009 influenza A (H1N1) virus was transmitted from humans to humans worldwide. The live attenuated monovalent A H1N1 vaccine (LAMV) for intranasal administration has shown promising immunogenicity and safety in clinical trials and for human use, but the experimental data based on LAMV is incomplete. In this study, using reverse genetic technology, we produced a cold-adapted (ca), live attenuated BJ/AA ca that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2009 pandemic A H1N1 isolate, A/Beijing/501/2009 virus (BJ501), and the remaining six internal gene segments from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). BJ/AA ca exhibited phenotypes of temperature sensitivity (ts), ca, and attenuation (att). The candidate BJ/AA ca was immunogenic in mice and induced strong mucosal secretory IgA (sIgA) in the respiratory tract. Two dosages of intranasal immunization induced robust HI antibodies and offered efficient protection against challenge by the wild-type (wt) 2009 pandemic A H1N1 (A/Beijing/501/2009 or A/California/07/2009) in mice and ferrets. These results support the evaluation of this vaccine made from a wt strain isolated in China for clinical trials.
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China. xiliangw@126.com
PengHui
P
Yang
YueQiang
Y
Duan
Cheng
C
Wang
Li
L
Xing
Xiao
X
Gao
Chong
C
Tang
DeYan
D
Luo
ZhongPeng
Z
Zhao
Weihong
W
Jia
Daxin
D
Peng
Xiufan
X
Liu
Xiliang
X
Wang
D000818:Animals; D002642:Chick Embryo; D005260:Female; D005289:Ferrets; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology; D013696:Temperature; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D007071:Immunoglobulin A, Secretory; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated