Browsing by Subject "IgG"
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Item Open Access Envelope-specific IgG Responses in HIV-infected Women(2018) Martinez, David RafaelA better understanding of 1) maternal HIV Envelope (Env)-specific IgG responses that are partially protective against vertical HIV transmission, and 2) factors that mediate the transplacental transfer of maternal protective IgG is needed to improve infant health in early life, in which maternal passively-acquired IgG mediates protection against neonatal infections. To understand maternal factors and IgG characteristics that mediate transplacental IgG transfer, we examined transplacental transfer efficiency determinants of maternal HIV and standard vaccine-antigen-specific IgG in a population of HIV-infected women, which have disrupted transplacental IgG transfer. Our findings suggest that maternal health factors and maternal IgG characteristics, such as binding to placentally expressed Fc receptors, IgG subclass frequency, and Fc region glycan profiles all mediate transplacental IgG transfer efficiency. We also identified maternal linear variable loop 3 (V3)-specific IgG binding and neutralizing responses targeting the C terminal region as partially protective against vertical transmission of HIV. These novel findings provide a roadmap of maternal factors and IgG characteristics as targets that can be harnessed to improve the transplacental IgG transfer of routinely-administered maternal vaccines and benchmarks for assessing maternal HIV vaccines that target the V3 loop.
Item Open Access Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection.(EBioMedicine) Astronomo, Rena D; Santra, Sampa; Ballweber-Fleming, Lamar; Westerberg, Katharine G; Mach, Linh; Hensley-McBain, Tiffany; Sutherland, Laura; Mildenberg, Benjamin; Morton, Georgeanna; Yates, Nicole L; Mize, Gregory J; Pollara, Justin; Hladik, Florian; Ochsenbauer, Christina; Denny, Thomas N; Warrier, Ranjit; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayapan, Sorachai; Kaewkungwal, Jaranit; Ferrari, Guido; Shaw, George M; Xia, Shi-Mao; Liao, Hua-Xin; Montefiori, David C; Tomaras, Georgia D; Haynes, Barton F; McElrath, Juliana MHIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching. For human vaginal explants, we developed a replication-competent, secreted NanoLuc reporter virus system and showed that CD4 binding site bnAbs b12 IgG1 and CH31 IgG1 and IgA2 isoforms potently blocked HIV-1JR-CSF and HIV-1Bal26 infection. However, IgG1 and IgA nnAbs, either alone or together, did not inhibit infection despite the presence of FcR-expressing effector cells in the tissue. In macaques, the CH31 IgG1 and IgA2 isoforms infused before high-dose SHIV challenge were completely to partially protective, respectively, while nnAbs (CH54 IgG1 and CH38 mIgA2) were non-protective. Importantly, in both mucosal models IgG1 isotype bnAbs were more protective than the IgA2 isotypes, attributable in part to greater neutralization activity of the IgG1 variants. These findings underscore the importance of potent bnAb induction as a primary goal of HIV-1 vaccine development.