Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques

• Published in: Nature medicine Vol. 15; no. 8; pp. 951 - 954
• Main Authors: Hessell, Ann J, Poignard, Pascal, Hunter, Meredith, Hangartner, Lars, Tehrani, David M, Bleeker, Wim K, Parren, Paul W H I, Marx, Preston A, Burton, Dennis R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2009; Nature Publishing Group
• Subjects: AIDS vaccines; Animal diseases; Animal models; Animal models in research; Animal vaccines; Animals; Antibodies, Viral - administration & dosage; Antibody Formation - physiology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chimera - immunology; Chimera - virology; Drug dosages; Exposure; Health aspects; HIV - immunology; HIV infection; Human immunodeficiency virus 1; Immunization - methods; Immunization Schedule; Infectious Diseases; letter; Macaca; Macaques; Metabolic Diseases; Molecular Medicine; Monkeys & apes; Neurosciences; Neutralization; Neutralization Tests; Prevention; SAIDS Vaccines - administration & dosage; Sexually transmitted diseases; Simian Acquired Immunodeficiency Syndrome - blood; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Immunodeficiency Virus - immunology; STD; Titrimetry; Treatment Outcome; Vaccines; Viruses; United States; Netherlands
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.1974

Neutralizing antibodies are thought to be crucial for HIV vaccine protection, but studies in animal models suggest that high antibody concentrations are required. This is a major potential hurdle for vaccine design. However, these studies typically apply a large virus inoculum to ensure infection in control animals in single-challenge experiments. In contrast, most human infection via sexual encounter probably involves repeated exposures to much lower doses of virus. Therefore, animal studies may have provided an overestimate of the levels of antibodies required for protection in humans. We investigated whether plasma concentrations of antibody corresponding to relatively modest neutralization titers in vitro could protect macaques from repeated intravaginal exposure to low doses of a simian immunodeficiency virus-HIV chimera (SHIV) that uses the CC chemokine receptor 5 (CCR5) co-receptor. An effector function-deficient variant of the neutralizing antibody was also included. The results show that a substantially larger number of challenges is required to infect macaques treated with neutralizing antibody than control antibody-treated macaques, and support the notion that effector function may contribute to antibody protection. Overall, the results imply that lower amounts of antibody than previously considered protective may provide benefit in the context of typical human exposure to HIV-1.