title: Seasonal H1N1 influenza virus infection induces cross-protective pandemic H1N1 virus immunity through a CD8-independent, B cell-dependent mechanism.
abstract: During the 2009 H1N1 influenza virus pandemic (pdmH1N1) outbreak, it was found that most individuals lacked antibodies against the new pdmH1N1 virus, and only the elderly showed anti-hemagglutinin (anti-HA) antibodies that were cross-reactive with the new strains. Different studies have demonstrated that prior contact with the virus can confer protection against strains with some degree of dissimilarity; however, this has not been sufficiently explored within the context of a pdmH1N1 virus infection. In this study, we have found that a first infection with the A/Brisbane/59/2007 virus strain confers heterologous protection in ferrets and mice against a subsequent pdmH1N1 (A/Mexico/4108/2009) virus infection through a cross-reactive but non-neutralizing antibody mechanism. Heterologous immunity is abrogated in B cell-deficient mice but maintained in CD8(-/-) and perforin-1(-/-) mice. We identified cross-reactive antibodies from A/Brisbane/59/2007 sera that recognize non-HA epitopes in pdmH1N1 virus. Passive serum transfer showed that cross-reactive sH1N1-induced antibodies conferred protection in naive recipient mice during pdmH1N1 virus challenge. The presence or absence of anti-HA antibodies, therefore, is not the sole indicator of the effectiveness of protective cross-reactive antibody immunity. Measurement of additional antibody repertoires targeting the non-HA antigens of influenza virus should be taken into consideration in assessing protection and immunization strategies. We propose that preexisting cross-protective non-HA antibody immunity may have had an overall protective effect during the 2009 pdmH1N1 outbreak, thereby reducing disease severity in human infections.
authors: Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China.
authors: Yuan
authors: Y
authors: Fang
authors: David
authors: D
authors: Banner
authors: Alyson A
authors: AA
authors: Kelvin
authors: Stephen S H
authors: SS
authors: Huang
authors: Christopher J
authors: CJ
authors: Paige
authors: Steven A
authors: SA
authors: Corfe
authors: Kevin P
authors: KP
authors: Kane
authors: R Chris
authors: RC
authors: Bleackley
authors: Thomas
authors: T
authors: Rowe
authors: Alberto J
authors: AJ
authors: Leon
authors: David J
authors: DJ
authors: Kelvin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002642:Chick Embryo; D056738:Cross Protection; D005260:Female; D005289:Ferrets; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D008800:Mexico / Q000453:epidemiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058873:Pandemics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016827:CD8 Antigens