title: Induction of mucosal HIV-specific B and T cell responses after oral immunization with live coxsackievirus B4 recombinants.
abstract: Given the limited success of clinical HIV vaccine trials, new vaccine strategies are needed for the HIV pipeline. The present study explored the novel concept that a live enteric virus, with limited disease potential, is a suitable vaccine vector to elicit HIV-specific immune responses in the gut mucosa of immunized mice. Two coxsackievirus B4 (CVB4) vaccine vectors were designed to induce HIV-specific B or T cell responses. A B cell immunogen, CVB4/gp41(2F5), was constructed by expressing an epitope from the membrane proximal external region (MPER) of gp41 as a structural peptide within a surface loop of a capsid protein of CVB4. The T cell immunogen, CVB4/p24(73(3)), was constructed previously by expressing a gag p24 sequence as a non-structural peptide at the amino-terminus of the CVB4 polyprotein. The CVB4/gp41(2F5) recombinant was antigenic in mice and elicited anti-gp41 antibodies in both the mucosal and systemic compartments. The route of immunization affected the antibody response since oral delivery of CVB4/gp41(2F5) induced anti-gp41 antibodies in the mucosal but not in the systemic compartment while parenteral delivery induced anti-gp41 antibodies in both compartments. In contrast, oral immunization with CVB4/p24(73(3)) elicited both mucosal and systemic gag p24-specific T cell responses. Since coxsackieviruses are ubiquitous in the human population, a key question is whether pre-existing vector immunity will inhibit the ability of a CVB4-based vaccine to induce HIV-specific immune responses. We show that pre-existing vector immunity did not preclude the development of mucosal anti-gp41 antibodies or gag p24-specific T cell responses after oral immunization with the CVB4/HIV recombinants. We suggest that the CVB4/HIV recombinants have the potential to be a viable vaccine product because of ease of delivery, safety, immunogenicity, ease of large-scale production, and storage conditions requiring cold-chain temperatures provided by refrigeration.
authors.affiliation: Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Gu
authors.forename: Cristy
authors.initials: C
authors.lastname: Stagnar
authors.forename: Lesya
authors.initials: L
authors.lastname: Zaichenko
authors.forename: Arlene I
authors.initials: AI
authors.lastname: Ramsingh
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004337:Drug Carriers; D029822:Enterovirus B, Human / Q000235:genetics* / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015700:HIV Envelope Protein gp41; D014614:Vaccines, Synthetic; C514787:gp41 protein, Human immunodeficiency virus 1