Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus.
HIV vaccine testing in primates is an important method for determining the possibility of vaccine benefit in humans. Goals of HIV-1 vaccination include establishing neutralizing antibodies and a strong CD8(+) T-cell response. We tested a novel vaccine conjugate for its ability to elicit relevant immune responses to HIV proteins and peptides in rhesus macaques. A neutralizing epitope, V3 loop peptide from HIV-1 envelope, was coupled to heat-inactivated Brucella abortus (V3-HKBA). Rhesus macaques were immunized with this conjugate in the anterior thigh. After two immunizations V3-specific antibodies were found in the sera and at mucosal sites. Neutralizing activity of these antibodies was demonstrated by syncytia inhibition assays. Cellular immune recall responses were demonstrated by antigen-specific induction of interferon-gamma and Regulation on Activation Noraml T Cell Expressed and Secreted (RANTES) secretion in vitro. These results confirm and extend preliminary studies in mice that suggest HKBA is an effective carrier that promotes neutralizing antibody secretion at relevant mucosal sites, as well as cellular immune responses that are correlated with viral protection.
Laboratory of Plasma Derivatives, Division of Hematology, Office of Blood Research and Review, Bethesda, MD 20892, USA. golding@cber.fda.gov
Nancy
N
Eller
Hana
H
Golding
Satoshi
S
Inoue
Paul
P
Beining
John
J
Inman
Natasha
N
Matthews
Dorothy E
DE
Scott
Basil
B
Golding
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002003:Brucella abortus / Q000276:immunology* / Q000821:virology; D018946:Chemokine CCL5 / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015726:Giant Cells / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D007106:Immune Sera / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
D016915:AIDS Vaccines; D018946:Chemokine CCL5; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007106:Immune Sera; D010446:Peptide Fragments; D007371:Interferon-gamma