Proteosomes, Emulsomes, and Cholera Toxin B Improve Nasal Immunogenicity of Human Immunodeficiency Virus gp160 in Mice: Induction of Serum, Intestinal, Vaginal, and Lung IgA and IgG

Abstract

Intranasal immunization of mice with human immunodeficiency virus (HIV) rgp160 complexed to proteosomes improved anti-gp160 serum IgA and IgG titers, increased the number of gp160 peptides recognized, and stimulated anti-gp160 intestinal IgA compared with immunization with uncomplexed rgp160 in saline. These enhanced responses were especially evident when either a bioadhesive nanoemulsion (emulsomes) or cholera toxin B subunit (CTB) was added to the proteosome-rgp160 vaccine. Furthermore, anti-gp160 IgG and IgA in vaginal secretions and fecal extracts were induced after intranasal immunization with proteosome-rgp160 delivered either in saline or with emulsomes. Formulation of uncomplexed rgp160 with emulsomes or CTB also enhanced serum and selected mucosal IgA responses. Induction of serum, vaginal, bronchial, intestinal, and fecal IgA and IgG by intranasal proteosome-rgp160 vaccines delivered in saline or with emulsomes or CTB is encouraging for mucosal vaccine development to help control the spread of HIV transmission and AIDS.

Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses

“…It has been shown that i.n. immunization effectively induces female genital tract immunity (34,48), and we did find that the most consistent protection was achieved by i.n. immunization with SHIV89.6.…”

Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles

“…Intranasal (i.n.) immunization induces local immunity, not only in the nasally associated lymphoid tissue and the lung but also in the female genital tract, in rodents (1,14,31,53,61) as well as humans and nonhuman primates (3,20,34,44). Similarly, intravaginal (IVAG) and intrarectal immunization of rodents also induces local immunity in the genital tract.…”

Targeting of Nasal Mucosa-Associated Antigen-Presenting Cells In Vivo with an Outer Membrane Protein A Derived fromKlebsiellapneumoniae

“…Recently, administration of vaccines by the nasal route has proven to be one of the most efficient ways of inducing both mucosal and systemic antibody responses in experimental animal models and human subjects (10,14,29,32). In addition, nasal immunization can induce immune responses in other mucosal sites, such as the vagina (2,20), a result which is of major interest for sexually transmitted diseases.…”

“…immunization with a soluble protein antigen alone does not usually elicit substantial antibody or cellular immune responses. These failures can be overcome by coadministration of antigens formulated with liposomes (5), biodegradable polymer microspheres (7), microparticles (1), outer membrane proteins (4), or proteosomes (9,20). In addition, adjuvants such as cholera toxin (CT), Escherichia coli heatlabile toxin (LT), or their B subunits (CTB and LTB, respectively) or, more recently, mutated forms of LT demonstrated efficacy in inducing mucosal and systemic responses when coupled to or mixed with several antigens (15,35).…”

“…Lung lavage fluids, nasal tract lavage fluids, and vaginal secretions were recovered as previously described (20,27). Enzyme-linked immunosorbent assays (ELISA) were performed essentially as described previously (26).…”