title: Single epitope mucosal vaccine delivered via immuno-stimulating complexes induces low level of immunity against simian-HIV.
abstract: The difficulty in developing an effective vaccine to contain the HIV/AIDS epidemic coupled with the fact that primary HIV-1 infection typically occurs via mucosal sites has increased emphasis on vaccine approaches that protect at mucosal surfaces. In this study we employed HIV and simian-HIV (SHIV)-derived T helper (Th) and cytotoxic T lymphocyte (CTL) single epitopes incorporated into immuno-stimulating complexes (ISCOM) as a candidate immunogens. Immunized rhesus macaques (Macaca mulatta) were challenged with CCR5-tropic SHIV(SF162p4). On the day of challenge, low levels of virus-neutralizing antibodies (Ab) and CTLs were detected in ISCOM-immunized macaques. Greater than 10(5) viral RNA copies per ml of plasma in 2/5 immunized and 3/4 control macaques were detected within 3 weeks post-challenge. Depletion of CD4+ T cells from gut-associated lymphoid tissues (GALT) was observed by post-challenge day (PCD) 14 in all macaques regardless immunization. Nonetheless, lower viral loads and relatively better preservation of peripheral CD4+ T cells following the SHIV infection was observed in ISCOM-immunized macaques. We predict that if coadministered with additional epitopes and/or more efficacious mucosal delivery system or route, HIV/SIV-derived peptide vaccines may have potential to elicit heterologous protection.
authors.affiliation: Tulane National Primate Research Center, Covington, LA 70433, USA.
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.forename: Mayra A
authors.initials: MA
authors.lastname: Cantu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Pyone P
authors.initials: PP
authors.lastname: Aye
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Karin
authors.initials: K
authors.lastname: Lovgren-Bengtsson
authors.forename: Karol
authors.initials: K
authors.lastname: Sestak
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D009500:Neutralization Tests; D010641:Phenotype; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000939:Epitopes; D015683:Gene Products, gag; D019394:Ki-67 Antigen; D018449:SAIDS Vaccines; D019014:fas Receptor; D007371:Interferon-gamma