? PROJECT 1 Much of the focus of vaccine-induced antibody responses to prevent HIV acquisition has been on IgG, the most common antibody isotype. However, previous work by this HIVRAD has found that combinations of IgA and IgG can inhibit SIV acquisition under circumstances where either alone shows no or limited inhibitory activity. This demonstrates the importance of considering the combined actions of the effector domains of multiple antibody isotypes in the successful developments of a vaccine. To gain mechanistic insights into the underlying ability of these antibody combinations to inhibit rectal acquisition in the rhesus macaque model, we will utilize our toolbox of microscopy-based reagents to gain insights into how acquisition is decreased or blocked. These tools allow us to directly examine the major components of the vaccine virus interaction at the mucosal surface including the labeling of antibodies, virus, and target cells, all in the proper anatomical configuration of the rectal compartment of a living animal. This plan of attack will take advantage of support from the project cores including macaque veterinary support, antibodies and virions, and the ability to do in vivo imaging via PET scan. New antibody combinations will come from data generated by project 2. More complicated vaccine induced responses will come from interactions with project 3. These studies will provide critical insights into the behavior of antibodies and their interactions with virions at mucosal surfaces. For example, we will determine the percentage of IgG at the rectal mucosa that is either generated systemically or locally. We will also determine the stability of antibodies within mucosal tissues. Understanding how antibody virus interactions influence the localization and phenotype of infected cells will further advance our knowledge of vaccine action. Understanding the in vivo mechanisms of IgA action against SHIV will also inform new possibilities in vaccine design. This information will inform vaccine development across a variety of pathogens. By providing mechanistic insights into the underlying effector functions of antibodies in preventing acquisition, we will advance our ability to develop a vaccine, which will protect humans from HIV acquisition.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1)
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University of Louisiana at Lafayette
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Tokatlian, Talar; Kulp, Daniel W; Mutafyan, Andrew A et al. (2018) Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci Rep 8:16527
Ruprecht, Ruth M; Lakhashe, Samir K (2017) Antibody-mediated immune exclusion of HIV. Curr Opin HIV AIDS 12:222-228
Ruprecht, Ruth M (2017) Anti-HIV Passive Immunization: New Weapons in the Arsenal. Trends Microbiol 25:954-956
Schneider, Jeffrey R; Carias, Ann M; Bastian, Arangaserry R et al. (2017) Long-term direct visualization of passively transferred fluorophore-conjugated antibodies. J Immunol Methods 450:66-72
Kulkarni, Viraj; Ruprecht, Ruth M (2017) Mucosal IgA Responses: Damaged in Established HIV Infection-Yet, Effective Weapon against HIV Transmission. Front Immunol 8:1581
Sholukh, Anton M; Watkins, Jennifer D; Vyas, Hemant K et al. (2015) Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge. Vaccine 33:2086-95
Lakhashe, Samir K; Byrareddy, Siddappa N; Zhou, Mingkui et al. (2014) Multimodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus. Vaccine 32:6527-36
Zhou, Mingkui; Ruprecht, Ruth M (2014) Are anti-HIV IgAs good guys or bad guys? Retrovirology 11:109
Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan et al. (2014) Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology 11:8
Bachler, Barbara C; Humbert, Michael; Lakhashe, Samir K et al. (2013) Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia. Retrovirology 10:63

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