Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS)
immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing
rabbits with a reduced number of oral doses and evaluating the host’s adaptive immune responses.
The duration of immunogenicity and subsequently protective efficacy was determined against wild type
heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with
HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae
were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype
specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains
were detected by immunoblot assay. Up-regulation of IL-12p35, IFN- and IL-10 mRNA expression was
detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS
in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level
of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the
immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae
challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided
complete protection in a rabbit model. These immunogens could be a broad spectrum non-living
vaccine candidate for human use in the near future.