Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: Implications for HIV-1 vaccine development

doi:10.1073/pnas.2436476100

Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: Implications for HIV-1 vaccine development

^*Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; ^†Viral Vaccines Program, Seattle Biomedical Research Institute, Seattle, WA 98109; and ^‡Department of Pathobiology, University of Washington, Seattle, WA 98109

Contributed by Malcolm A. Martin, October 7, 2003

Abstract

Passive transfer of high-titered antiviral neutralizing IgG, known to confer sterilizing immunity in pig-tailed monkeys, has been used to determine how soon after virus exposure neutralizing antibodies (NAbs) must be present to block a simian immunodeficiency virus (SIV)/HIV chimeric virus infection. Sterilizing protection was achieved in three of four macaques receiving neutralizing IgG 6 h after intravenous SIV/HIV chimeric virus inoculation as monitored by PCR analyses of and attempted virus isolations from plasma, peripheral blood mononuclear cell, and lymph node specimens. In the fourth animal, the production of progeny virus was suppressed for >4 weeks. A delay in transferring NAbs until 24 h after virus challenge resulted in infection in two of two monkeys. These results suggest that even if a vaccine capable of eliciting broadly reactive NAbs against primary HIV-1 were at hand, the Abs generated must remain at, or rapidly achieve, high levels within a relatively short period after exposure to virus to prevent the establishment of a primate lentivirus infection.

Footnotes

↵ § To whom correspondence should be addressed at: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 4, Room 315, Bethesda, MD 20892. E-mail: malm{at}nih.gov.
Abbreviations: NAb, neutralizing antibody; PBMC, peripheral blood mononuclear cell; RT, reverse transcriptase; SIV, simian immunodeficiency virus; SHIV, SIV/HIV chimeric virus; TCID₅₀, tissue culture 50% infective dose.