Format

Send to

Choose Destination
Nat Commun. 2015 Apr 10;6:6565. doi: 10.1038/ncomms7565.

Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
Department of Biochemistry, Columbia University, New York, New York 10032, USA.
3
1] Department of Biochemistry, Columbia University, New York, New York 10032, USA [2] State Key Laboratory of Organ Failure Research and National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
4
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
5
Department of Microbiology and Immunology, Boston University, Boston, Massachusetts 02118, USA.
6
AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, Maryland 21702, USA.
7
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
8
Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.

Abstract

Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.

PMID:
25858157
PMCID:
PMC4403371
DOI:
10.1038/ncomms7565
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Secondary source ID, Grant support

Publication type

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center