Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Parks, KR; MacCamy, AJ; Trichka, J; Gray, M; Weidle, C; Borst, AJ; Khechaduri, A; Takushi, B; Agrawal, P; Guenaga, J; Wyatt, RT; Coler, R; Seaman, M; LaBranche, C; Montefiori, DC; Veesler, D; Pancera, M; McGuire, A; Stamatatos, L
Published Date
- December 3, 2019
Published In
Volume / Issue
- 29 / 10
Start / End Page
- 3060 - 3072.e7
PubMed ID
- 31801073
Pubmed Central ID
- PMC6936959
Electronic International Standard Serial Number (EISSN)
- 2211-1247
Digital Object Identifier (DOI)
- 10.1016/j.celrep.2019.10.071
Language
- eng
Conference Location
- United States