Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization
Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization
Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2∗02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.
- University of Washington United States
- Harvard University United States
- Duke University United States
- Washington State University United States
- University of Mary United States
Male, B-Lymphocytes, QH301-705.5, env Gene Products, Human Immunodeficiency Virus, Antibodies, Monoclonal, Receptors, Antigen, B-Cell, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, Article, Mice, Polysaccharides, CD4 Antigens, HIV-1, Animals, Female, Immunization, Biology (General), Immunoglobulin Heavy Chains, Broadly Neutralizing Antibodies
Male, B-Lymphocytes, QH301-705.5, env Gene Products, Human Immunodeficiency Virus, Antibodies, Monoclonal, Receptors, Antigen, B-Cell, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, Article, Mice, Polysaccharides, CD4 Antigens, HIV-1, Animals, Female, Immunization, Biology (General), Immunoglobulin Heavy Chains, Broadly Neutralizing Antibodies
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