Oral Attenuated Salmonella Enterica Serovar Typhimurium Vaccine Expressing Codon-Optimized HIV Type 1 Gag Enhanced Intestinal Immunity in Mice

Oral immunization is a safe and easily applicable route to induce mucosal immunity to HIV infection. We examined the ability of oral attenuated Salmonella typhimurium (ST) vaccine expressing Gag for the efficiency of generating Gag-specific mucosal IgA and CD8⁺ T cell responses in intestinal lymphoid tissues. By optimizing the codon of HIV-1 gag to the preferred codon bias of Salmonella, the expression of Gag in Salmonella was dramatically improved. The oral ST-Gag vaccine by itself was not so powerful and induces little Gag-specific CD8⁺ T cell responses in the intestine. Nevertheless, we found that it potentiates otherwise weak intestinal CD8 ⁺ T cell responses in nasally primed mice with Gag p24 and cholera toxin adjuvant. Thus, the oral delivery of Salmonella expressing Gag would be utilized in combination with other parenteral vaccine to direct and strengthen intestinal HIV-specific CTL responses.