Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques

J. Pablo Jaworski, James Kobie, Zachary Brower, Delphine C. Malherbe, Gary Landucci, William F. Sutton, Biwei Guo, Jason S. Reed, Enrique J. Leon, Flora Engelmann, Bo Zheng, Al Legasse, Byung Park, Mary Dickerson, Anne D. Lewis, Lois M.A. Colgin, Michael Axthelm, Ilhem Messaoudi, Jonah B. Sacha, Dennis R. BurtonDonald N. Forthal, Ann J. Hessell, Nancy L. Haigwood

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIVinfected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression.

Original languageEnglish (US)
Pages (from-to)10447-10459
Number of pages13
JournalJournal of virology
Volume87
Issue number19
DOIs
StatePublished - Oct 28 2013

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Jaworski, J. P., Kobie, J., Brower, Z., Malherbe, D. C., Landucci, G., Sutton, W. F., Guo, B., Reed, J. S., Leon, E. J., Engelmann, F., Zheng, B., Legasse, A., Park, B., Dickerson, M., Lewis, A. D., Colgin, L. M. A., Axthelm, M., Messaoudi, I., Sacha, J. B., ... Haigwood, N. L. (2013). Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques. Journal of virology, 87(19), 10447-10459. https://doi.org/10.1128/JVI.00049-13