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The potential of the human immune system to develop broadly neutralizing HIV-1 antibodies: implications for vaccine development.
Zhang, Yu; Yuan, Tingting; Li, Jingjing; Zhang, Yanyu; Xu, Jianqing; Shao, Yiming; Chen, Zhiwei; Zhang, Mei-Yun.
Afiliação
  • 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.
AIDS ; 27(16): 2529-39, 2013 Oct 23.
Article em En | MEDLINE | ID: mdl-24100711
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_transmissiveis Assunto principal: Anticorpos Anti-HIV / HIV-1 / Vacinas contra a AIDS / Anticorpos Neutralizantes Limite: Humans Idioma: En Revista: AIDS Assunto da revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Ano de publicação: 2013 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 1_ASSA2030 Problema de saúde: 1_doencas_transmissiveis Assunto principal: Anticorpos Anti-HIV / HIV-1 / Vacinas contra a AIDS / Anticorpos Neutralizantes Limite: Humans Idioma: En Revista: AIDS Assunto da revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Ano de publicação: 2013 Tipo de documento: Article País de afiliação: China
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