Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
Protection of rhesus macaques from homologous and heterologous SHIV challenge using oligomeric gp160.
Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:50. Unique Identifier : AIDSLINE MED/97927034 VanCott TC; Lewis M; Kaminski R; Mascola J; Kalyanaraman V; Pragman S; Frampton L; Yalley-Ogunro J; Greenhouse J; Lu Y; Jenkins S; Richardson C; Ulrich T; Wassef N; Alving C; Lowell G; Birx D; Henry M. Jackson Foundation, Rockville, MD. Fax: (301) 762-4177.
Abstract:
Protection of rhesus macaques from i.v. challenge with SHIV(HXBc2) was evaluated using affinity purified, oligomeric gp160 (ogp160-IIIB) or monomeric gp120-IIIB formulated with alhydrogel, monophosphoryl lipid A (MPL) or polyphosphazene. Previous studies in rabbits demonstrated the ability of ogp160 formulated in MPL to elicit antibodies preferentially reactive with native forms of gp120 and which neutralized several primary HIV-1 isolates. Formulation with liposomes, MPL or proteosomes elicited high titered serum as well as vaginal, lung, intestinal and salivary IgG/IgA antibodies also directed preferentially to natively folded gp120. Vaginal and lung wash from the ogp160/proteosome immunized mice were capable of neutralizing HIV-1(MN). We sought to determine whether non-human primates immunized intramuscularly with o-gp160-IIIB were protected against homologous and heterologous i.v. SHIV challenge. Monkeys n=30) were immunized i.m. at 0, 1 and 6 months with either adjuvant only (n=9), 100 micrograms of gp120-IIIB formulated in alhydrogel (n=3) or MPL (n=3) or 100 micrograms of ogp160-IIIB formulated in alhydrogel (n=5), MPL (n=5) or polyphosphazene n=5) and challenged two weeks after the 3rd immunization. Sera from all monkeys immunized with ogp160-IIIB had greater than 90% neutralizing antibody titers against HIV-1 from strains IIIB and RF and several also neutralized MN at the time of challenge. 2/5 and 1/5 monkeys immunized with ogp160-IIIB in polyphosphazene and MPL, respectively, and with the highest HIV-1(IIIB) neutralizing antibody titers, were completely protected from SHIV infection. Partial protection, defined by a greater than 10-fold reduction in total viral RNA from the mean of the adjuvant-only controls over the first 6 weeks was obtained in 8/21 monkeys receiving either gp120 or ogp160. 2/2 of the protected monkeys were reboosted at month 12 with 300 micrograms o-gp160-IIIB in polyphosphazene, and completely protected against SHIV(MN) challenge.
Keywords: *AIDS Vaccines/IMMUNOLOGY *HIV Envelope Protein gp160/IMMUNOLOGY *HIV Infections/PREVENTION & CONTROL *Simian Acquired Immunodeficiency Syndrome/PREVENTION & CONTROL 971130
M97B1188
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Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
