Heterosubtypic immunity to influenza A virus: where do we stand?

Abstract

Influenza A virus (IAV) strains are denoted by the subtype of their hemagglutinin (HA) and neuraminidase (NA) virion surface proteins. Major changes in HA subtype among strains circulating in humans are referred to as "antigenic shift". Antigenic shift can occur by two means; direct transmission of a zoonotic strain to humans or through reshuffling of the segmented genome in cells co-infected with animal and human strains. The lack of circulating anti-HA antibodies in human populations to a novel IAV results in extremely high frequency of illness and the potential for severe morbidity and mortality on a world-wide basis; the dreaded pandemic. Such pandemics could be partially controlled by developing a vaccine that generates effective heterosubtypic immunity (HSI) based on immune recognition of IAV antigens conserved across all viral strains. While it has long been known that T cells exhibit such broad cross-reactive specificity that could provide effective HSI, recent animal studies suggest a potential role for antibodies as well. Here we review current knowledge of the mechanisms contributing to HSI to influenza and speculate on the potential for this approach to contribute to public health.

Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza

“…Both the virus and the immune response to it have been extensively characterized at the molecular, immunological and epidemiological levels [1][2][3][4][5][6][7][8][9][10]. Current influenza vaccines focus on the generation of antibodies to the surface proteins haemagglutinin (HA) and, to a lesser extent, neuraminidase.…”

Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

“…However, due to antigenic drift, these antibodies fail to protect against new antigenic variants of the same type or subtype and are rarely cross reactive against other influenza virus strains [3]. Thus, annual vaccine reformulation is necessary to ultimately maintain immunity against seasonal influenza viruses [4,5]. Furthermore, antigenic drift renders uniform population wide vaccination campaigns, that have led to the control of measles and smallpox, ineffective for influenza virus [6].…”

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

“…The latter has been shown to afford various degrees of protection in animal models and humans, depending on the combination of subtypes of IAV used for priming and challenge infection, respectively (Benton et al, 2001;Grebe et al, 2008;Kreijtz et al, 2007Kreijtz et al, , 2009McMichael et al, 1983;Nguyen et al, 1999;O'Neill et al, 2000;Schulman & Kilbourne, 1965;Seo & Webster, 2001). …”