Vancott TC, Lewis M, Kaminski R, Mascola J, Kalyanaraman V, Veit SD, Lu Y, Jenkins S, Richardson C, Ulrich T, Birx DL; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 204 (abstract no. 755).

Henry M. Jackson Foundation, Rockville, MD.

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. We sought to determine whether such antibodies could be elicited in non-human primates and whether this response was protective against SHIV challenge. Monkeys (n=30) were immunized i.m. at 0, 1 and 6 months with either adjuvant only (n=9), 100 ug of gp120-IIIB formulated in alhydrogel (n=3) or MPL (n=3) or 100 ug 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 4 months after challenge as assessed by negative viral co-cultures and DNA PCR and the absence of any detectable amnestic response or seroconversion to SIV p27. Partial protection as defined by greater than 20-fold reduction in total viral RNA from the mean of the adjuvant-only controls over the first 6 weeks was obtained in 14/21 monkeys receiving either gp120 or ogp160. These data demonstrate the utility of SHIV/macaque challenge system and demonstrate complete and partial protection using an oligomeric gp160 protein.

Publication Types:

• Meeting Abstracts

Keywords:

• Adjuvants, Immunologic
• Adjuvants, Pharmaceutic
• Animals
• HIV Envelope Protein gp120
• HIV-1
• Humans
• Immunization
• MPL protein, human
• Macaca mulatta
• Proto-Oncogene Proteins
• RNA, Viral
• Rabbits
• Receptors, Cytokine
• Simian immunodeficiency virus
• Vaccination
• immunology

Other ID:

• 97926186

UI: 102223195

From Meeting Abstracts