Influenza Pandemics of 1918 and 2009

A Comparative Account

Madhu Khanna; Latika Saxena; Ankit Gupta; Binod Kumar; Roopali Rajput


Future Virology. 2013;8(4):335-342. 

In This Article

Serology & Antigenic Characteristics

Hancock et al. have shown the presence of detectable antibodies against 2009 H1N1 between 8 and 14 days after onset of infection, with more than 85% of the subjects tested having antibody titers of 32 or greater by hemagglutination inhibition after 15 days.[30] Initial reports suggested that seasonal influenza vaccines failed to elicit any cross-reactivity against the 2009 pandemic virus in humans, suggesting considerable antigenic divergence. However, this observation was later contradicted by studies such as one in Mexico involving 60 confirmed cases of A(H1N1)pdm09 influenza virus.[31] This study further indicates that the 2008–2009 trivalent inactivated vaccine (A/Brisbane/59/2007 [H1N1]-like, A/Brisbane/10/2007 [H3N2]-like and B/Florida/4/2006-like antigen) may provide some protection against A(H1N1)pdm09 virus. Moreover, none of the vaccinated cases of influenza A/H1N1 died, indicating that seasonal vaccination might protect against the most severe forms of the disease. The proportion of patients who died among vaccinated cases was significantly lower than among unvaccinated cases. In another study from Canada, it was observed that prior receipt of 2008–2009 trivalent inactivated vaccine was associated with increased risk of medically attended pH1N1 illness during spring–summer 2009.[32]

Interestingly, several of the immunogenic peptides derived from the A(H1N1)pdm09 influenza virus were representative of the 1918 H1N1 pandemic virus rather than the recent seasonal influenza strains.[33] It has been shown that the A(H1N1)pdm09 monovalent vaccine protects mice from 1918 Spanish influenza virus.[34] In a separate study, immunization with the seasonal trivalent influenza vaccine of 2010–2011 protected ferrets from the reconstructed 1918 virus.[35] These observations are suggestive of a certain degree of similarity between the two pandemic strains. The HA genes of the two pandemic strains are different from those of the seasonal viruses in terms of glycosylation sites. All of the seasonal strains show the presence of at least two glycosylation sites at the top of their HAs, whereas the two pandemic strains are 'bald', lacking these sites. The absence of glycosylation sites at the top of these molecules account for the difference in immune response, as these sugars form a cloud around the HA, masking the ability of the antibody to recognize the right amino acid.[36]

The H1 HA molecules have four distinct antigenic sites: Sa, Sb, Ca and Cb.[37] The crystal structure of the HA of A/Cal/04/2009 H1N1 virus reveals that the antigenic structure, especially within the Sa antigenic site, is extremely similar to that of the 1918 H1N1 virus. 2D1, an antibody from the survivor of the 1918 pandemic that neutralizes both 1918 and 2009 pandemic virus, reveals an epitope that is conserved in both forms of the pandemic virus.[103]

The HA gene of the 2009 pandemic virus has acquired a proline-to-serine substitution at position 200, which might have resulted in decreased virulence compared with the 1918 pandemic virus.

The NA gene facilitates influenza virus release by the cleavage of the terminal sialic acid residues that are receptors of the viruses HA protein. The NA gene of the 2009 pandemic virus differs by 18.2% from the seasonal H1N1 virus, which possibly rendered the seasonal vaccines ineffective against this novel virus.[38]