1. CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques.
- Author
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Sarkar S, Spencer DA, Barnette P, Pandey S, Sutton WF, Basu M, Burch RE, Cleveland JD, Rosenberg AF, Rangel-Moreno J, Keefer MC, Hessell AJ, Haigwood NL, and Kobie JJ
- Subjects
- Animals, Antibodies, Bacterial biosynthesis, Antibodies, Bacterial immunology, Antibodies, Viral immunology, Antibody-Dependent Cell Cytotoxicity, Broadly Neutralizing Antibodies immunology, CD4-Positive T-Lymphocytes immunology, Cross Reactions, Female, Germinal Center immunology, HIV Antibodies immunology, HIV Envelope Protein gp160 immunology, HIV-1 immunology, Immunization, Secondary, Male, Phagocytosis, Simian Acquired Immunodeficiency Syndrome immunology, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Acquired Immunodeficiency Syndrome virology, Simian Immunodeficiency Virus immunology, Vaccine Development, Vaccines, Synthetic, Viral Load, env Gene Products, Human Immunodeficiency Virus immunology, AIDS Vaccines, Broadly Neutralizing Antibodies biosynthesis, HIV Antibodies biosynthesis, Macaca mulatta immunology
- 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sarkar, Spencer, Barnette, Pandey, Sutton, Basu, Burch, Cleveland, Rosenberg, Rangel-Moreno, Keefer, Hessell, Haigwood and Kobie.)
- Published
- 2021
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