Cross-reactive immunity of Influenza A/H5N1 strains in mice & humans

Session VI – Kusters, Inca

Cross-reactive immunity of Influenza A/H5N1 strains in mice & humans
I. Kusters*, C. Caillet, M. Denis
 sanofi pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L’Etoile, France
*inca.kusters@sanofipasteur.com
Possible strategies to prepare for the next influenza pandemic include the stockpiling of H5N1 vaccines for use in the event that a pandemic is declared. An open question is the level of protection that these stockpiled vaccines will provide against the pandemic strain. It is thus important to assess the ability of vaccine candidates to elicit broad cross-reactive immune responses, which will be important in the early response to an emerging pandemic.
The factors possibly influencing cross-reactivity include the vaccine strain, the adjuvant used, and the level of pre-existing immunity. We evaluated the ability of adjuvanted H5N1 vaccines against various H5N1 strains (clade 1 A/Vietnam/1194/2004/NIBRG-14, clade 2.1 A/Indonesia/05/2005 and clade 2.2 A/Bar-Headed Goose/Qinghai Lake/1a/2005) to induce cross-reactive immune responses in mice and humans.
In mice, clade 2 vaccines induced higher homologous hemagglutination inhibition (HI) immune responses compared with clade 1 vaccine, and the clade 2.2 vaccine induced the highest heterologous HI titers. In humans, the clade 1 and 2.1 vaccines elicited similar levels of heterologous HI titers. However, using the seroneutralization assay which is considered to be more sensitive than the HI assay, the clade 2.1 vaccine induced higher homologous titers. In mice, pre-existing influenza immunity was not found to influence HI responses to adjuvanted H5N1 vaccines: groups of influenza-naïve mice and mice primed with trivalent seasonal influenza vaccine mounted comparable HI titers after H5N1 vaccination. H1N1 has been described as the most antigenically-related seasonal influenza strain to H5N1. We therefore evaluated the impact of pre-existing H1N1 antibodies on the response to H5N1 vaccination in humans. As in mice, pre-existing H1N1 immunity in humans did not appear to increase the homologous or the cross-reactive immune responses against a clade 2.1 strain following administration of a clade 1 vaccine. However, in both mice and humans clade 1 H5N1 vaccination increased the preexisting H1N1 HI response. In humans, a second clade 1 H5N1 vaccination did not induce a further increase in H1N1 antibody titers.

These findings on the heterologous and homologous immune responses induced by various H5N1 vaccines have implications for the efficacy of current H5N1 vaccines against a potential future pandemic strain.