151. Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.
- Author
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Smith AJ, Wietgrefe SW, Shang L, Reilly CS, Southern PJ, Perkey KE, Duan L, Kohler H, Müller S, Robinson J, Carlis JV, Li Q, Johnson RP, and Haase AT
- Subjects
- Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antibody Formation immunology, Antigen-Antibody Complex immunology, CD4-Positive T-Lymphocytes immunology, Cell Movement immunology, Cervix Uteri virology, Female, Gene Expression Profiling, HIV Envelope Protein gp41 immunology, Immunity, Innate, Immunoglobulin G biosynthesis, Immunoglobulin G immunology, Lymphocyte Activation immunology, Macaca mulatta, Mucous Membrane immunology, SAIDS Vaccines administration & dosage, Simian Acquired Immunodeficiency Syndrome immunology, Simian Acquired Immunodeficiency Syndrome prevention & control, Vaccination, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Vagina virology, Cervix Uteri immunology, Receptors, IgG immunology, SAIDS Vaccines immunology, Simian Immunodeficiency Virus immunology, Vagina immunology
- Abstract
Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic's epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. In this study, we identify blocking CD4(+) T cell recruitment to thereby inhibit local expansion of infected founder populations as a second correlate of protection. Virus-specific immune complex interactions with the inhibitory FcγRIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex-FcγRIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine., (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Published
- 2014
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