Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.
Read more about eLife’s peer review process.Editors
- Reviewing EditorBryan BrysonMassachusetts Institute of Technology, Cambridge, United States of America
- Senior EditorJoshua SchifferFred Hutch Cancer Center, Seattle, United States of America
Reviewer #1 (Public review):
Summary:
Based on previous work showing that viral evolution follows reproducible patterns in diverse animals, the authors sought to examine whether the antibody response operates under similar constraints. By analyzing over 17,000 B cells isolated from 6 monkeys at 3 different time points, the authors convincingly show that the immune response does follow specific patterns of responses to different classes of epitopes based on the infecting virus. Moreover, each of these clusters has characteristic (cross-) binding and neutralization properties. Importantly, these classes are independent of the underlying immunogenetics, which (as expected) vary significantly between monkeys. This last point is particularly relevant for vaccine design, as it means that immunogens may not need to be as narrowly focused on specific germline genes as previously thought.
Strengths:
The large number of B cells cultured for this study is a particular strength, as is the fact that they were isolated in an antigen-unbiased fashion. The experiments are well-designed and comprehensive.
Weaknesses:
The genetic element is a relatively minor component overall and more qualitative than quantitative. It would be nice to investigate other properties of the repertoire like CDRH3 length and possible public clones, as well.
Reviewer #2 (Public review):
Summary:
Song et al. comprehensively analyzed the SHIV-infected macaque B cell repertoires and commonalities among their antibody responses, despite their diverse genetic background. They suggest these studies would inform HIV-1 vaccine design.
Strengths:
This study is well-designed and used proper analysis methods, and the figures are clear and effectively presented.
Weaknesses:
However, it tends to overstate its novelty and significance, emphasizing points that are relatively obvious (e.g., different classes of antibodies can recognize a common epitope) and appears to have been overwritten and unnecessarily fancy ("conceptually analogous to ecomorph evolution", "epitopic convergence"). Moreover, some limitations of the rhesus macaque model and the differences between bnAbs and nAbs should be discussed. That said, the underlying data are solid and important in their detail, and the manuscript will be a useful resource for HIV-1 vaccine and pathogen studies.
