Characterization of antibodies specific for hemagglutinin and neuraminidase proteins of the 1918 and 2009 pandemic H1N1 viruses.
Serologic studies have detected protective immunity against 2009 pandemic H1N1 influenza virus (H1N1-2009) in some people. However, further study of preexisting immunity has been complicated by the complexity of the human immunological background. Here, we immunized mice with HA- and NA-encoding plasmids. The cross-neutralizing activity of the anti-HA antisera and the effect of the anti-NA antisera on viral infectivity were evaluated using H1N1-1918- and 2009-pseudotyped particles (pps) and an H1N1-2009 isolate. Antibodies to H1N1-2009 HA (09HA) neutralized pps harboring 09HA or H1N1-1918 HA (18HA); similarly, antibodies to 18HA neutralized pps harboring 18HA or 09HA. Antibodies to 09HA and 18HA also neutralized the H1N1-2009 virus with high efficiency. Antibodies to H1N1-1918 NA (18NA) or H1N1-2009 NA (09NA) both enhanced the infectivity of pps harboring 09NA and 18NA. Although anti-09NA and -18NA antibodies significantly reduced cytopathic effects in multiple-cycle infection assays, conversely, these antibodies enhanced the infectivity of H1N1-2009 in single-cycle infection assays. Our study demonstrates the existence of cross-protection between antibodies against these two antigenically related virus strains and shows that anti-NA antibodies have a dual effect that requires reexamination of their role in human immunity.
Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
Yuan
Y
Liu
Xiaoqing
X
Liu
Jing
J
Fang
Xiaona
X
Shen
Wei
W
Chen
Xiaojing
X
Lin
Huaifang
H
Li
Wenjie
W
Tan
Yue
Y
Wang
Ping
P
Zhao
Zhongtian
Z
Qi
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology*; D002460:Cell Line; D056738:Cross Protection; D003429:Cross Reactions; D003588:Cytopathogenic Effect, Viral; D004285:Dogs; D005260:Female; D005822:Genetic Vectors; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology*; D009500:Neutralization Tests; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; C458881:hemagglutinin fusogenic peptide, influenza virus; C487630:NA protein, influenza A virus; D009439:Neuraminidase