Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.
The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.
Duke Scholars
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- Macaca
- Humans
- HIV-1
- Developmental Biology
- Cell Adhesion Molecules
- CD4 Antigens
- Broadly Neutralizing Antibodies
- Animals
- AIDS Vaccines
- 32 Biomedical and clinical sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Macaca
- Humans
- HIV-1
- Developmental Biology
- Cell Adhesion Molecules
- CD4 Antigens
- Broadly Neutralizing Antibodies
- Animals
- AIDS Vaccines
- 32 Biomedical and clinical sciences