The feline immunodeficiency virus (FIV) model provides a system to study lentivirus transmission, virus kinetics, pathogenesis, host responses, and immune dysfunction in a natural, out-bred host, under controlled conditions with specific-pathogen-free animals. The diversity of primary FIV strains can be exploited to mirror the range of disease manifestations associated with HIV infection. FIV is infectious via intravenous, intraperitoneal, intradermal, or subcutaneous injection as well as by atraumatic instillation onto the oral, vaginal, or rectal mucosa. Together, these features allow investigators to model specific aspects of HIV infection in a highly relevant and relatively inexpensive animal model. Well-developed areas of the FIV model include: (1) transmission of cell-associated as well as cell-free virus; (2) mucosal infectivity and immunopathogenesis; (3) vertical transmission; (4) acquired immunodeficiency including defects of the innate immune system; (5) thymic dysfunction; (6) neurotropism and neuropathogenesis; (7) host-virus interactions and the role of specific gene products; (8) efficacy of antiviral therapy; and (9) efficacy and immune correlates of experimental vaccines. This review will encompass areas specific to transmission and immunopathogenesis.

Lactic acid bacteria (LAB) have been utilized since the 1990s for therapeutic heterologous gene expression. The ability of LAB to elicit an immune response against expressed foreign antigens has led to their exploration as potential mucosal vaccine candidates. LAB vaccine vectors offer many attractive advantages: simple, noninvasive administration (usually oral or intranasal), the acceptance and stability of genetic modifications, relatively low cost, and the highest level of safety possible. Experimentation using LAB of the genus Lactobacillus has become popular in recent years due to their ability to elicit strong systemic and mucosal immune responses. This article reviews Lactobacillus vaccine constructs, including Lactobacillus species, antigen expression, model organisms, and in vivo immune responses, with a primary focus on viral and bacterial antigens.

Lactobacillusspecies are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use ofL. gasserias a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies ofLactobacillusbeing studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modifiedL. gasseri. L. gasseriprimarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile ofL. gasseriand the immunogenicity of the vector, a plasmid containingfliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production.In vivostudies established that treatment withL. gasseriled to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modifiedL. gasseriled to a significant decrease in the percentage of FoxP3⁺colonic lymphocytes. Taken together, these data clarify the interaction ofL. gasseriwith the host immune system and support further investigation of thein vivoimmunogenicity ofL. gasseriexpressing both flagellin and candidate vaccine antigens.

Oral vaccines that elicit a mucosal immune response may be effective against human immunodeficiency virus type 1 (HIV-1) because its transmission occurs mainly at the mucosa. The aim of this study was to construct recombinant Lactobacillus for oral delivery of oral vaccines against HIV-1 and to evaluate their immunogenicity. A recombinant Lactobacillus acidophilus strain expressing the HIV-1 Gag on the bacterial cell surface was established by fusion with the signal peptide and anchor motif of a mucus binding protein (Mub) from L. acidophilus with or without coexpression of Salmonella enterica serovar Typhimurium flagellin (FliC) fused to a different Mub signal peptide and anchor. Using HEK293 cells engineered to express Toll-like receptor 5 (TLR5), the biological activity of FliC on the bacterial cell surfaces was determined. The surface-exposed flagellin retained its TLR5-stimulating activity, suggesting that the recombinant strain with Gag and FliC dual display might provide a different immunopotency than the strain expressing only Gag. The immunological properties of the recombinant strains were assessed by coculture with human myeloid dendritic cells (DCs). The heterologous antigens on the cell surface affected maturation and cytokine responses of DCs. Acquired immune responses were also investigated by intragastric immunization of mice. The enzyme-linked immunosorbent spot assay showed induction of gamma interferon-producing cells at local mucosa after immunization of mice with the Gag-producing strain. Meanwhile, the immunization with L. acidophilus displaying both Gag and FliC resulted in an increase of Gag-specific IgA-secreting cells. These results suggested that the Gag-displaying L. acidophilus elicited specific immune responses and the coexistence of FliC conferred an adjuvant effect on local IgA production.