AEGiS-13IAC: A neutralizing human monoclonal antibody protects macaques against vaginal challenge with a pathogenic R5 SHIV.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

A neutralizing human monoclonal antibody protects macaques against vaginal challenge with a pathogenic R5 SHIV.

Int Conf AIDS 2000 Jul 9-14; 13:37 (abstract no.. LbPeA7022)

Parren P, Marx P, Cheng-Mayer C, Harouse J, Moore J, Burton D;;; The Scripps Research Institute, Department of Immunology, La Jolla, CA. Fax: 858-784-8360, E-mail: parren@scripps.edu.

BACKGROUND: Neutralizing antibodies against HIV-1 will most likely play an important role in a vaccine against HIV-1 and may be useful in passive immunoprophylaxis of HIV-1 infection. Passive transfer of neutralizing antibodies in animals models has been shown to provide protection against HIV-1 challenge. Most HIV-1 infections occur by transmission of a pathogenic R5 virus across a mucosal surface. However to date no studies have been performed that investigate the level of protection that neutralizing antibodies can provide against such challenge.

METHODS: Neutralizing mAb b12 was administered i.v. after which rhesus macaques were challenged vaginally with a pathogenic R5 virus: SHIV-162P. Two groups of four monkeys received neutralizing mAb b12 at a high dose (25 mg/kg) and a low dose (5 mg/kg) respectively. Two control monkeys received a control antibody at 25 mg/kg.

RESULTS: Both control animals became infected. The animals treated with the high dose of b12 were sterilely protected, as were two out of the four animals treated with the low dose. The two animals in this group that became infected showed a lower and delayed viremia compared to the controls. More detailed analyses are underway and will be reported.

CONCLUSIONS: Neutralizing antibody can interrupt mucosal transmission of a pathogenic R5 virus. Complete protection was achieved at antibody serum concentrations of approximately 300 ug/ml and partial protection at 50 ug/ml. Since b12 neutralizes the challenge virus at approximately 1 ug/ml in vitro (90%), complete protection is only achieved at serum concentrations which essentially neutralize all of the challenge virus. The high concentrations required contrast with a recent study in which protection against vaginal challenge with an R5X4 virus (SHIV89.6PD) was achieved at lower neutralizing antibody concentrations. As SHIV 89.6PD is primarily infectious via use of CXCR4, this may indicate that it is more difficult to protect against mucosal transmission of R5 than of X4 viruses.

Keywords: AEGIS, Macaca, Vagina, HIV-1, Macaca mulatta, HIV Infections, Hominidae, Naphthalenes, Antibodies, Monoclonal, protect, Human, Animal, Female, In Vitro, immunology, AIDS
000709
LbPeA7022