Immunity to Pre-1950 H1N1 Influenza Viruses Confers Cross-Protection against the Pandemic Swine-Origin 2009 A (H1N1) Influenza Virus

Abstract

The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50–60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse-adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine-origin 2009 H1N1 influenza virus.

T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model

“…Previous analysis of human serum samples found neutraliz- (34). Thus, our inability to detect cross-reactive HAI activity against CA/E3/09 in PR8-infected sera is essentially comparable with these studies.…”

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

“…Depending on the study and region analyzed, individuals under the age of 25 years represented 45% to 60% of infected subjects, though the pathogenic effects of H1N1 virus infection were most pronounced in individuals more than 60 years old (4,36). These findings, as well as recent immunological studies from our laboratory and other laboratories (11,17,20,22,25,33,39,48,51,52,55,61,62), suggest that previous encounters with vaccines or viruses provide immunological advantages and immunological memory in the population despite the "serological distance" between the hemagglutinin (HA) and neuraminidase (NA) proteins of seasonal and pandemic strains.…”

Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses

“…This theory has been validated in human and animal models, although debate still exists in the field over a mechanism governing the phenomenon. It is possible that the immunological mechanisms that bias one's response to early exposures to virus may be, in part, explained by the induction of stalk-specific antibodies (30,31).…”