CD4+ T Cells Are Dispensable for Induction of Broad Heterologous HIV Neutralizing Antibodies in Rhesus Macaques

• Published in: Frontiers in immunology Vol. 12; p. 757811
• Main Authors: Sarkar, Sanghita, Spencer, David A, Barnette, Philip, Pandey, Shilpi, Sutton, William F, Basu, Madhubanti, Burch, Reuben E, Cleveland, John D, Rosenberg, Alexander F, Rangel-Moreno, Javier, Keefer, Michael C, Hessell, Ann J, Haigwood, Nancy L, Kobie, James J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20-10-2021
• Subjects: AIDS Vaccines; Animals; Antibodies, Bacterial - biosynthesis; Antibodies, Bacterial - immunology; Antibodies, Viral - immunology; antibody; Antibody-Dependent Cell Cytotoxicity; B cell; Broadly Neutralizing Antibodies - biosynthesis; Broadly Neutralizing Antibodies - immunology; CD4+ T cell; CD4-Positive T-Lymphocytes - immunology; Cross Reactions; env Gene Products, Human Immunodeficiency Virus - immunology; Female; Germinal Center - immunology; HIV - human immunodeficiency virus; HIV Antibodies - biosynthesis; HIV Antibodies - immunology; HIV Envelope Protein gp160 - immunology; HIV-1 - immunology; Immunization, Secondary; Immunology; Macaca mulatta - immunology; Male; Phagocytosis; rhesus; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - immunology; vaccine; Vaccine Development; Vaccines, Synthetic; Viral Load; B cell; vaccine; CD4+ T cell; HIV - human immunodeficiency virus; antibody; rhesus; neutralizing
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.757811

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.