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- Title
B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
- Authors
Yacoob, Christina; Lange, Miles Darnell; Cohen, Kristen; Lathia, Kanan; Feng, Junli; Glenn, Jolene; Carbonetti, Sara; Oliver, Brian; Vigdorovich, Vladimir; Sather, David Noah; Stamatatos, Leonidas
- Abstract
Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies. Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions). The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization. These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization. Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited. Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites. The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003–0.02%) of total B cells. Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
- Subjects
AIDS vaccines; HIV antibodies; B cell receptors; HIV-1 glycoprotein 120; VIRAL envelope proteins
- Publication
PLoS Pathogens, 2018, Vol 14, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1007120