Induction of Strong Anti-HIV Cellular Immunity by a Combination of Clostridium Perfringens Expressing HIV Gag and Virus Like Particles

Poonam      Pegu; Ruth      Helmus; Phalguni      Gupta; Patrick      Tarwater; Lori      Caruso; Chengli      Shen; Ted      Ross; Yue      Chen

Abstract

The lower gastrointestinal tract is a major mucosal site of HIV entry and initial infection. Thus, the induction of strong cellular immune responses at this mucosal site will be an important feature of an effective HIV vaccine. We have used a novel prime-boost vaccination approach to induce immune responses at mucosal sites. Orally delivered recombinant Clostridium perfringens expressing HIV-1 gag (Cp-Gag) was evaluated for induction of HIV-1 Gag specific T cell responses in a prime-boost model with intranasal inoculation of HIV-1 virus like particles (VLP). HIV-1 specific cellular immune responses in both the effector (Lamina propria) and inductive sites (Peyers patches) of the gastrointestinal (GI) tract were significantly higher in mice immunized using Cp-Gag and VLPs in a prime-boost approach compared to mice immunized with either Cp-Gag or VLPs alone. Such cellular immune response was found to be mediated by both CD8+ and CD4+ T cells. Such a strong mucosal immune response could be very useful in developing a mucosal vaccine against HIV-1.

Keywords: HIV, mucosal vaccine, Clostridium perfringens, virus like particles, mucosal immunity, gastrointestinal tract, immune responses, Adjuvants, Immunization, Sample Collection