This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The role of maternal neutralizing antibodies (NAbs) in determining whether an infant becomes infected during Mother to Child Transmission (MTCT) of HIV-1 is unclear. Higher levels of both autologous and heterologous NAbs are associated with non- transmission, and NAb-resistant isolates are transmitted. This topic is timely and important, as there is increasing interest in testing vaccines or immunotherapies during the early breastfeeding period, when postpartum transmission risk is highest and drug therapy can select resistant isolates. Would the augmentation of the passively transferred maternal NAbs with human monoclonals (mAbs) be effective in this setting? To address some of these questions experimentally outside the clinic, we have established a perinatal SHIV transmission model in M. nemestrina and in M. mulatta. In this model, we have observed durable plasma virus control in newborn macaques infected orally with SHIV- SF162P3 in the presence of sub-sterilizing levels of IgG that neutralized the challenge virus. We have shown that passively transferred NAbs can accelerate de novo anti-SHIV NAbs, similar to experiments in the SIV model. In this renewal, we propose to shift the focus toward understanding the mechanisms behind these observations.
WIn AIM 1, we plan to comprehensively evaluate the anti- SHIV T- and B-cell responses in SHIV-IgG-treated and control adult macaques for magnitude, timing, avidity, specificity, conformation-dependence, and breadth.
In AIM 2, we plan to characterize the development of specific B cell responses in macaques with accelerated versus normal neutralizing responses by cloning antibody variable regions from individual antibody-secreting B cells (ASCs) and reconstructing them as human IgG1 antibodies. By this method, we can capture the diversity of the early IgG response and characterize the Env-specific mAbs for antiviral activity including neutralization and ADCVI.
In AIM 3, we will test the effectiveness of new HIV Env- specific broadly neutralizing mAbs in complementing maternal SHIV-IgG as a more effective passive immunotherapy in newborns. We propose that these experiments will yield valuable information about the mechanisms of antibodies in controlling HIV in vivo and may inform potential immunotherapies to limit MTCT in the clinic.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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Oregon Health and Science University
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Su, Weiping; Foster, Scott C; Xing, Rubing et al. (2017) CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation. J Biol Chem 292:4434-4445
Lima, Fernanda B; Leite, Cristiane M; Bethea, Cynthia L et al. (2017) Progesterone increased ?-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration. Brain Res 1663:1-8
Slayden, Ov Daniel (2016) Translational In Vivo Models for Women's Health: The Nonhuman Primate Endometrium--A Predictive Model for Assessing Steroid Receptor Modulators. Handb Exp Pharmacol 232:191-202
Chadderdon, S M; Belcik, J T; Bader, L et al. (2016) Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes (Lond) 40:1600-1603
Dufour, Brett D; McBride, Jodi L (2016) Intravascular AAV9 Administration for Delivering RNA Silencing Constructs to the CNS and Periphery. Methods Mol Biol 1364:261-75
Meyer, Thomas J; Held, Ulrike; Nevonen, Kimberly A et al. (2016) The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery. Genome Biol Evol 8:3209-3225
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C et al. (2016) Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun 7:11138
Sylwester, Andrew; Nambiar, Kate Z; Caserta, Stefano et al. (2016) A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev 158:14-22
Laws, L H; Parker, C E; Cherala, G et al. (2016) Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion. Am J Transplant 16:3139-3149

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