Enhancing protection against highly pathogenic H5N1 avian influenza A viruses (170.31)

• Published in: The Journal of immunology (1950) 2012-05, Vol.188 (1_Supplement), p.170-170.31
• Main Authors: McGargill, Maureen, Keating, Rachael, Lukens, John, Hertz, Tomer, Harris, Tarsha, Edwards, Benjamin, Creasy, Blaine, Doherty, Peter, Thomas, Paul
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.170.31

Highly pathogenic H5N1 avian influenza A viruses pose a serious threat for a deadly pandemic. Vaccination is the most effective strategy for controlling influenza, however it is not possible to predict which H5N1 variants may acquire the ability to transmit efficiently between humans, and conserved epitopes between different subtypes do not induce sufficient immunity. Thus, a strategy to increase the efficacy of universal vaccines is essential for preventing a deadly pandemic. Others demonstrated that the immunosuppressive drug, rapamycin, paradoxically increased the number of memory T cells during LCMV infection. Thus, we examined whether rapamycin increases the number of memory T cells during influenza infection, and consequently enhances protection against a secondary infection with a heterosubtypic H5N1 strain. Mice were immunized with HKx31 (H3N2), treated with rapamycin for 30 days, and challenged with a modified H5N1 virus, ΔVn1203. We found rapamycin protected mice from a lethal ΔVn1203 infection, but not in the absence of a primary infection. Interestingly, rapamycin increased the number of influenza-specific CD8 T cells after the primary and secondary infection. However, memory CD8 T cells were not required for protection. Rather, CD4 T cells and B cells were critical for the enhanced survival following rapamycin treatment. These data suggest that rapamycin protects against a highly pathogenic, heterosubtypic influenza infection by altering the antibody response.