| First Author | Parks KR | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 10 | Pages | 3060-3072.e7 |
| PubMed ID | 31801073 | Mgi Jnum | J:300355 |
| Mgi Id | MGI:6489049 | Doi | 10.1016/j.celrep.2019.10.071 |
| Citation | Parks KR, et al. (2019) Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization. Cell Rep 29(10):3060-3072.e7 |
| abstractText | 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. |
