Attenuated dendritic cell function in BALB/c mice following HPAI vaccination results from failed C-type lectin receptor signaling (P4309)

Abstract

Abstract Highly pathogenic avian influenza (HPAI) has an approximate 60% fatality rate in humans. In the United States, a vaccine for HPAI has been manufactured and stockpiled using FDA approved methods for seasonal vaccines. Compared to seasonal vaccines, the HPAI vaccine is less immunogenic in humans despite similar production methods. We developed a mouse model of influenza vaccination to examine differences in the host immune response to these vaccines. Mice that received the seasonal vaccine produced a robust neutralizing antibody response whereas no neutralizing antibodies were detected following HPAI vaccination. Dendritic cells (DCs) cultured with HPAI vaccine had decreased expression of activation markers CD40 and CD86, and produced significantly lower levels of cytokines IL-6, IL-12, and TNF-α compared to those treated with seasonal vaccine. C-type lectin receptors have been implicated as a class of pattern recognition receptors in innate immunity and immunization. Pretreatment with mannan diminished cytokine induction by DCs in a dose dependent manner following seasonal but not HPAI vaccine treatment, suggesting a role for C-type lectin receptors in DC activation by influenza vaccines. These findings implicate a potential mechanism for attenuated DC function following HPAI vaccination and may explain the lack of immunogenicity of the currently approved HPAI vaccine.