Rhesus Macaque B-Cell Responses to an HIV-1 Trimer Vaccine Revealed by Unbiased Longitudinal Repertoire Analysis.

TitleRhesus Macaque B-Cell Responses to an HIV-1 Trimer Vaccine Revealed by Unbiased Longitudinal Repertoire Analysis.
Publication TypeJournal Article
Year of Publication2015
AuthorsDai K, He L, Khan SN, O'Dell S, McKee K, Tran K, Li Y, Sundling C, Morris CD, Mascola JR, Karlsson Hedestam GB, Wyatt RT, Zhu J
JournalMBio
Volume6
Issue6
Paginatione01375-15
Date Published11/03/2015
ISSN2150-7511
Abstract

UNLABELLED: Next-generation sequencing (NGS) has been used to investigate the diversity and maturation of broadly neutralizing antibodies (bNAbs) in HIV-1-infected individuals. However, the application of NGS to the preclinical assessment of human vaccines, particularly the monitoring of vaccine-induced B-cell responses in a nonhuman primate (NHP) model, has not been reported. Here, we present a longitudinal NGS analysis of memory B-cell responses to an HIV-1 trimer vaccine in a macaque that has been extensively studied by single B-cell sorting and antibody characterization. We first established an NHP antibodyomics pipeline using the available 454 pyrosequencing data from this macaque and developed a protocol to sequence the NHP antibody repertoire in an unbiased manner. Using these methods, we then analyzed memory B-cell repertoires at four time points of NHP immunization and traced the lineages of seven CD4-binding site (CD4bs)-directed monoclonal antibodies previously isolated from this macaque. Longitudinal analysis revealed distinct patterns of B-cell lineage development in response to an HIV-1 trimer vaccine. While the temporal B-cell repertoire profiles and lineage patterns provide a baseline for comparison with forthcoming HIV-1 trimer vaccines, the newly developed NHP antibody NGS technologies and antibodyomics tools will facilitate future evaluation of human vaccine candidates.

IMPORTANCE: The nonhuman primate model has been widely used in the preclinical assessment of human vaccines. Next-generation sequencing of B-cell repertoires provides a quantitative tool to analyze B-cell responses to a vaccine. In this study, the longitudinal B-cell repertoire analysis of a rhesus macaque immunized with an HIV-1 trimer vaccine revealed complex B-cell lineage patterns and showed the potential to facilitate the evaluation of future HIV-1 vaccines. The repertoire sequencing technologies and antibodyomics methods reported here can be extended to vaccine development for other human pathogens utilizing the nonhuman primate model.

DOI10.1128/mBio.01375-15
Alternate JournalMBio
PubMed ID26530382
PubMed Central IDPMC4631801
Grant ListP01 AI104722 / AI / NIAID NIH HHS / United States
P01 AI104722 / AI / NIAID NIH HHS / United States
R01 AI102766 / AI / NIAID NIH HHS / United States
R01AI102766 / AI / NIAID NIH HHS / United States
UM1AI 100663 / AI / NIAID NIH HHS / United States
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