Background: The development and testing of oral mucosal, prophylactic HIV vaccines represent novel prevention approaches against the global HIV/AIDS epidemic. As HIV transmission occurs first through primary virus replication in the lymphoid tissue of rectal, genital and oral mucosae, targeting these sites with mucosal vaccines are effective methods of inducing local and systemic immunity against HIV infection. In this study, lactic acid bacteria, common oral commensal microbes, were tested as recombinant HIV vaccine vectors for oral mucosal immunization and immunogenicity assessment in mice.
Advance: NIDCR-supported investigators established an oral mucosal, prophylactic HIV vaccine by using the Lactobacillus acidophilus strain, which co-expressed on its cell surface the HIV-1 antigen Gag and the Salmonella enterica serovar Typhimurium flagellin FliC. The recombinant strain co-expressing Gag and FliC yielded stronger immunopotency compared to the strain expressing only Gag. In vitro testing of the immunological properties of these vaccines was done by co-culturing them with human myeloid dendritic cells (hmDCs). The heterologous antigens expressed by these recombinant strains induced hmDCs to differentiate and secrete cytokines. In vivo immunogenicity testing of these vaccines was done by intragastric immunization of mice. Vaccination with the Gag-producing strain alone induced secretion of interferon gamma by lymphocytes at local mucosa. In contrast, vaccination of mice with the recombinant L. acidophilus expressing Gag and FliC yielded an enhanced Gag-specific IgA response by B lymphocytes. These results demonstrated the immunogenicity of an oral, mucosal HIV vaccine prototype, consisting of Gag/FliC-expressed in L. acidophilus, which also contained an adjuvant effect on local IgA production triggered by FliC.
Public Impact Statement/Significance: Immunogenic and protective oral prophylactic HIV vaccines are novel and feasible in preventing HIV infection.
Publication Citation: Kajikawa A, Zhang L, Long J, Nordone S, Stoeker L, LaVoy A, Bumgardner S, Klaenhammer T, Dean G (2012). Construction and Immunological Evaluation of Dual Cell Surface Display of HIV-1 Gag and Salmonella enterica Serovar Typhimurium FliC in Lactobacillus acidophilus for Vaccine Delivery. Clin. Vaccine Immunol., 19(9):1374-81. Link to PDF Article: