Persistence of HIV-1 Env-Specific Plasmablast Lineages in Plasma Cells after Vaccination in Humans

Autor: James J. Kobie, Madhubanti Basu, Christopher F. Fucile, Alexander F. Rosenberg, Jane L. Liesveld, Fritzlaine C. Roche, Michael C. Keefer, Michael S. Piepenbrink, Catherine A. Bunce, Bo Zheng, Ann J. Hessell, David A. Spencer, Czestochowa Francois
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports Medicine, Vol 1, Iss 2, Pp 100015-(2020)
Cell reports medicine
ISSN: 2666-3791
Popis: SUMMARY Induction of persistent HIV-1 Envelope (Env) specific antibody (Ab) is a primary goal of HIV vaccine strategies; however, it is unclear whether HIV Env immunization in humans induces bone marrow plasma cells, the presumed source of long-lived systemic Ab. To define the features of Env-specific plasma cells after vaccination, samples were obtained from HVTN 105, a phase I trial testing the same gp120 protein immunogen, AIDSVAX B/E, used in RV144, along with a DNA immunogen in various prime and boost strategies. Boosting regimens that included AIDSVAX B/E induced robust peripheral blood plasmablast responses. The Env-specific immunoglobulin repertoire of the plasmablasts is dominated by VH1 gene usage and targeting of the V3 region. Numerous plasmablast-derived immunoglobulin lineages persisted in the bone marrow >8 months after immunization, including in the CD138+ long-lived plasma cell compartment. These findings identify a cellular linkage for the development of sustained Env-specific Abs following vaccination in humans.
Graphical Abstract
In Brief In a phase I HIV vaccine trial, Basu et al. show the robust response of HIV Env gp120-specific peripheral blood plasmablasts immediately after vaccination, dominated by VH1 gene usage and V3 region-targeting Abs. They also define persistent linkage of these Env-reactive lineages to the bone marrow CD138+ LLPC compartment.
Databáze: OpenAIRE