RT Journal Article
SR Electronic
T1 Mixed Origins: HIV gp120-specific memory develops from pre-existing memory and naïve B cells following vaccination in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.01.458551
DO 10.1101/2021.09.01.458551
A1 Madhubanti Basu
A1 Michael S. Piepenbrink
A1 Christopher Fucile
A1 Catherine A. Bunce
A1 Li-Xing Man
A1 Jane Liesveld
A1 Alexander F. Rosenberg
A1 Michael C. Keefer
A1 James J. Kobie
YR 2021
UL http://biorxiv.org/content/early/2021/09/01/2021.09.01.458551.abstract
AB The most potent and broad HIV envelope (Env)-specific antibodies often when reverted to their inferred germline versions representing the naïve B cell receptor, fail to bind Env suggesting that the initial responding B cell population is not exclusively comprised of a naïve population, but also a pre-existing cross-reactive antigen-experienced B cell pool that expands following Env exposure. Previously we isolated gp120-reactive monoclonal antibodies (mAbs) from participants in HVTN 105, an HIV vaccine trial. Using deep sequencing VH-lineage tracking we identified several of these mAb lineages in pre-immune peripheral blood. Several of these pre-immune lineages also persisted in the bone marrow, including CD138+ long-lived plasma cell compartment, ∼7 months after the final vaccination. The majority of the pre-immune lineage members included IgM, however IgG and IgA members were also prevalent and exhibited somatic hypermutation. These results suggest that vaccine-induced gp120-specific antibody lineages originate from both naïve and cross-reactive memory B cells.Competing Interest StatementThe authors have declared no competing interest.