Time dependence of protective post-exposure prophylaxis with human monoclonal antibodies against pathogenic SHIV challenge in newborn macaques

• Published in: Virology (New York, N.Y.) Vol. 358; no. 1; pp. 69 - 78
• Main Authors: Ferrantelli, Flavia, Buckley, Kathleen A, Rasmussen, Robert A, Chalmers, Alistair, Wang, Tao, Li, Pei-Lin, Williams, Alison L, Hofmann-Lehmann, Regina, Montefiori, David C, Cavacini, Lisa A, Katinger, Hermann, Stiegler, Gabriela, Anderson, Daniel C, McClure, Harold M, Ruprecht, Ruth M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.02.2007
• Subjects: Animals; Animals, Newborn; Antibodies, Monoclonal - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; CD4 Lymphocyte Count; Disease Models, Animal; HIV Antibodies - immunology; HIV Infections - prevention & control; Immunity, Cellular; Immunization, Passive; Infectious Disease; Macaca; Macaca mulatta; Neutralizing monoclonal antibodies; Oral infection; Passive immunization; Pathogenic simian–human immunodeficiency virus (SHIV); Post-exposure prophylaxis; Primates; Rhesus macaques; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Immunodeficiency Virus - immunology; Simian/human immunodeficiency virus; Survival Analysis; Time Factors; Viral Load; Viremia; Rhesus macaques; Post-exposure prophylaxis; Oral infection; Passive immunization; Pathogenic simian–human immunodeficiency virus (SHIV); Neutralizing monoclonal antibodies
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.07.056

Abstract In a primate model of postnatal virus transmission, we have previously shown that 1 h post-exposure prophylaxis (PEP) with a triple combination of neutralizing monoclonal antibodies (nmAbs) conferred sterilizing protection to neonatal macaques against oral challenge with pathogenic simian–human immunodeficiency virus (SHIV). Here, we show that nmAbs can also partially protect SHIV-exposed newborn macaques against infection or disease, when given as 12 or 24 h PEP, respectively. This work delineates the potential and the limits of passive immunoprophylaxis with nmAbs. Even though 24 h PEP with nmAbs did not provide sterilizing immunity to neonatal monkeys, it contained viremia and protected infants from acute disease. Taken together with our results from other PEP studies, these data show that the success of passive immunization depends on the nmAb potency/dose and the time window between virus exposure and start of immunotherapy.