Preexisting Immunity to 2009 H1N1 Influenza

The severity of an influenza pandemic is linked not only to the pathogenicity of new influenza strains but also to the degree of immunity that the population has to those new strains. Initial analyses of the current pandemic suggested that only individuals born before 1957 have preexisting cross-reactive antibodies to the 2009 pandemic influenza A (H1N1) virus (JW Infect Dis Sep 16 2009). Yet, the severity of disease during this pandemic has not been markedly greater than what seasonal influenza typically causes.

To better understand this discordance, investigators compared the B- and T-cell epitopes of the 2009 H1N1 virus with all known epitopes of H1N1 viruses that had circulated between 1988 and 2008. Of the 26 B-cell epitopes identified in past H1N1 viruses, only 8 (31%) were found in the 2009 H1N1 virus. However, 57 (41%) of the 139 CD4 T-cell epitopes in past H1N1 viruses — and 54 (69%) of the 78 CD8 T-cell epitopes in these viruses — were found in the current pandemic virus. The conserved epitopes existed predominantly within internal structural proteins of the 2009 H1N1 virus, rather than in the surface-exposed hemagglutinin and neuraminidase proteins.

In a separate analysis, the investigators directly assessed memory T-cell immunity, using peripheral blood mononuclear cell samples collected from 20 adult volunteers in 2007. They found that immune response to the conserved CD4 and CD8 T-cell epitopes in the 2009 H1N1 strain was on par with immune response to other epitopes in past H1N1 strains and that CD8 T-cell response was more robust than CD4 T-cell response.