Rhesus macaque B-cell responses to an HIV-1 trimer vaccine revealed by unbiased longitudinal repertoire analysis

Year
2015
Type(s)
Authors
Dai, K. He, L. Khan, S. N. O'Dell, S. McKee, K. Tran, K. Li, Y. Sundling, C. Morris, C. D. Mascola, J. R. Hedestam, G. B. K. Wyatt, Richard Zhu, Jiang
Source
mBio 2015 6:e01375-15
Url
http://dx.doi.org/10.1128/mBio.01375-15

Abstract

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.

 

Technology Platform

Next-Generation Sequencing

Research Topics

B cell Repertoire Analysis