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The potential of the human immune system to develop broadly neutralizing HIV-1 antibodies: implications for vaccine development.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, Yu Yuan, Tingting Li, Jingjing Zhang, Yanyu Xu, Jianqing Shao, Yiming Chen, Zhiwei Zhang, Mei-Yun
Description	Country affiliation: China Author Affiliation: Zhang Y ( aAIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong bInstitutes of Biomedical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai cDivision of Research on Virology and Immunology, National Center for AIDS/STD Control and Prevention, China CDC, Beijing, China.)
Abstract	OBJECTIVES AND DESIGN: Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) and cDNA levels by deep sequencing followed by high-throughput sequence analysis to determine the frequencies of putative germline antibody genes of known HIV-1 monoclonal bnAbs (bnmAbs). METHODS: Combinatorial gDNA and cDNA antibody libraries were constructed using the gDNAs and mRNAs isolated from uninfected and HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries were deep sequenced and sequences analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index.action). The frequencies of putative germline antibodies of known bnmAbs in the gDNA and cDNA libraries were determined. RESULTS AND CONCLUSION: The human gDNA antibody libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries, indicating that the human gDNA antibody gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnAbs. The frequencies of the heavy and kappa and lambda light chain variable regions with identical V(D)J recombinations to known HIV-1 bnmAbs were extremely low in human antibody gene repertoires. However, we found relatively high frequencies of the heavy and kappa and lambda light chain variable regions that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. B-cells bearing B-cell receptors of such heavy and kappa and lambda light chain variable regions may be stimulated to induce HIV-1 bnAbs.
File Format	HTM / HTML
ISSN	02699370
e-ISSN	14735571
DOI	10.1097/QAD.0000000000000015
Journal	AIDS
Issue Number	16
Volume Number	27
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2013-10-23
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Immunology Aids Vaccines Immunology Antibodies, Neutralizing Genetics Hiv Antibodies Hiv-1 Gene Library Hiv Infections Healthy Volunteers High-throughput Nucleotide Sequencing Leukocytes, Mononuclear Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Immunology Immunology and Allergy

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