Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.
Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by 1 of 16 different simian-human immunodeficiency viruses (SHIVs). We identified the V2 apex region of the envelope (Env) as the most common bNAb target and a subset of Envs that preferentially elicited these antibodies. In 10 macaques, we delineated Env-antibody coevolution from B cell priming to bNAb development. Antibody phylogenies revealed permissive developmental pathways guided by evolving Envs that contained few mutations in or near the V2 apex C-strand, which were a sensitive indicator of apex-targeted responses. The absence of such mutations reflected a failure in bNAb priming. These results indicate that efficiency of B cell priming, and not complexities in Env-guided affinity maturation, is a primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as vaccine platforms.
Duke Scholars
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- env Gene Products, Human Immunodeficiency Virus
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Macaca mulatta
- Humans
- HIV-1
- HIV Infections
- HIV Antibodies
- B-Lymphocytes
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Macaca mulatta
- Humans
- HIV-1
- HIV Infections
- HIV Antibodies
- B-Lymphocytes