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Abstract
ANTIBODY PROTECTION OF MACAQUES AGAINST VAGINAL CHALLENGE WITH A PATHOGENIC R5 HIV-1/SIV CHIMERIC VIRUS REQUIRES COMPLETE NEUTRALIZATION OF VIRUS
PARREN P, MARX P, LUCKAY A, HAROUSE J, CHENG-MAYER C, MOORE J, BURTON D
Objectives: A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as coreceptor, appear to be crucial in transmission of HIV-1 in humans. Here we show that passive transfer of the human broadly HIV-1-neutralizing monoclonal antibody b12 can completely protect macaques against vaginal challenge with the R5 virus SHIV162P.
Methods: The challenge virus SHIV162P (grown in rhesus PBMC) was titrated using three groups of three monkeys and it was determined that all monkeys became infected and developed high plasma viremias following vaginal challenge with 300 TCID50. This challenge dose was used in the following experiments. Three groups of four rhesus macaques were injected intravenously with varying doses of the neutralizing antibody mAb b12 and challenged vaginally six hours later with SHIV162P. Animals were closely monitored for the relevant virological, hematological and immunological parameters.
Results: Four of four monkeys given 25 mg/kg of b12 6h prior to challenge showed no evidence of viral replication. Two of four monkeys given 5 mg/kg of b12 were similarly protected whereas the other two showed significantly reduced and delayed viremias compared to control animals. All four monkeys treated with 1 mg/kg became infected and showed viremias close to those of control animals. Antibody b12 serum concentrations at the time of virus challenge corresponded to approximately 400 (25 mg/kg), 80 (5 mg/kg) and 15 (1 mg/kg) times in vitro (90%) neutralization titers.
Conclusions: Therefore complete protection against R5 HIV-1 mucosal challenge required essentially complete neutralization of the infecting virus. This suggests a vaccine based on antibody alone would need to elicit serum neutralizing antibody titers (90%) of the order of 1:400 to achieve sterile protection but that lower titers around 1:100 could provide significant benefit.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
9
Suggested Citation
"PARRENP, et al.
ANTIBODY PROTECTION OF MACAQUES AGAINST VAGINAL CHALLENGE WITH A PATHOGENIC R5 HIV-1/SIV CHIMERIC VIRUS REQUIRES COMPLETE NEUTRALIZATION OF VIRUS.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
9"
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