@article{86bd0a20f67e4619a6cba1dff62cc4e0,
title = "CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques",
abstract = "Induction of broadly neutralizing antibodies (bNAbs) is a major goal for HIV vaccine development. HIV envelope glycoprotein (Env)-specific bNAbs isolated from HIV-infected individuals exhibit substantial somatic hypermutation and correlate with T follicular helper (Tfh) responses. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 plasmids and gp140 trimeric proteins derived from an HIV-1 infected subject that developed bNAbs, we determined the characteristics of the Env-specific humoral response in vaccinated rhesus macaques in the context of CD4+ T cell depletion. Unexpectedly, both CD4+ depleted and non-depleted animals developed comparable Tier 1 and 2 heterologous HIV-1 neutralizing plasma antibody titers. There was no deficit in protection from SHIV challenge, no diminution of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis, or antibody-dependent complement deposition in the CD4+ depleted animals. These collective results suggest that in the presence of diminished CD4+ T cell help, HIV neutralizing antibodies were still generated, which may have implications for developing effective HIV vaccine strategies.",
keywords = "B cell, CD4+ T cell, HIV - human immunodeficiency virus, antibody, neutralizing, rhesus, vaccine",
author = "Sanghita Sarkar and Spencer, {David A.} and Philip Barnette and Shilpi Pandey and Sutton, {William F.} and Madhubanti Basu and Burch, {Reuben E.} and Cleveland, {John D.} and Rosenberg, {Alexander F.} and Javier Rangel-Moreno and Keefer, {Michael C.} and Hessell, {Ann J.} and Haigwood, {Nancy L.} and Kobie, {James J.}",
note = "Funding Information: This research was partially funded by the National Institutes of Health (NIH) (5R01AI117787, 5R01DE027245 to JK; P51-OD011092, U42-OD023038 to NH), and the University of Alabama at Birmingham Center for AIDS Research P30 AI027767. Funding Information: The authors are grateful for Dr. Catarina Hioe for providing V3 reagents, Dr. David Evans for providing cells for ADCC, the technical assistance provided by Dr. Michael Piepenbrink and Christopher Bates, the technical resources provided by the UAB CFAR Basic Sciences Core, the biostatistics assistance provided by the UAB CFAR, and the expert animal care provided by the veterinary staff of the ONPRC. The Anti-CD4 [CD4R1] antibody used in this study was provided by the NIH Nonhuman Primate Reagent Resource (P40 OD028116). Publisher Copyright: Copyright {\textcopyright} 2021 Sarkar, Spencer, Barnette, Pandey, Sutton, Basu, Burch, Cleveland, Rosenberg, Rangel-Moreno, Keefer, Hessell, Haigwood and Kobie.",
year = "2021",
month = oct,
day = "20",
doi = "10.3389/fimmu.2021.757811",
language = "English (US)",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}