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    Two closely related Env antigens from the same patient elicited different spectra of neutralizing antibodies against heterologous HIV-1 isolates

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    Authors
    Vaine, Michael
    Duenas-Decamp, Maria J.
    Peters, Paul J.
    Liu, Qin
    Arthos, James
    Wang, Shixia
    Clapham, Paul R.
    Lu, Shan
    UMass Chan Affiliations
    Program in Molecular Medicine, and Department of Molecular Genetics and Microbiology
    Graduate School of Biomedical Sciences
    Department of Preventive and Behavioral Medicine
    Department of Cancer Biology
    Center for AIDS Research
    Program in Immunology and Virology
    Infectious Diseases and Immunology
    Clinical and Population Health Research
    Department of Medicine
    Document Type
    Journal Article
    Publication Date
    2011-03-01
    Keywords
    Animals
    Antibodies, Neutralizing
    Brain
    HIV Antibodies
    HIV Infections
    HIV-1
    Humans
    Immunization
    Immunization, Secondary
    Lymph Nodes
    Rabbits
    Viral Tropism
    env Gene Products, Human Immunodeficiency Virus
    dosage
    Life Sciences
    Medicine and Health Sciences
    Women's Studies
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126169/
    Abstract
    Identification of immunogens capable of eliciting broadly neutralizing antibody (NAb) responses against HIV-1 is a major goal toward the development of an AIDS vaccine. Despite significant progress in understanding the structural features of the HIV-1 envelope glycoprotein (Env) and the discovery of multiple broadly neutralizing monoclonal antibodies with defined antigenic structures, the design of optimal Env immunogens to elicit broad NAbs remains a major challenge. As the structural determinants of Env immunogenicity remain unclear, we assessed two closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features to identify what may result in a favorable immunogenic profile. One Env, B33, isolated from brain, was highly macrophage tropic with a high CD4 affinity, while the other, LN40, isolated from the lymph nodes, was poorly macrophage tropic with a low CD4 affinity. Using a DNA prime-protein boost approach, rabbits primed with LN40 Env antigen had a NAb response against heterologous primary isolates, while B33 Env antigens were capable of eliciting NAbs against only homologous and sensitive viral isolates. Further analysis revealed that the specificity of NAbs elicited by the LN40 antigen mapped to limited residues within or flanking the CD4 binding site. Certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs. This progress will facilitate the rational design of effective HIV-1 vaccine formulations with optimal Env antigens.
    Source

    J Virol. 2011 May;85(10):4927-36. Epub 2011 Mar 16. Link to article on publisher's site

    DOI
    10.1128/JVI.00081-11
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50991
    PubMed ID
    21411542
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.00081-11
    Scopus Count
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    Morningside Graduate School of Biomedical Sciences Scholarly Publications
    UMass Chan Faculty and Researcher Publications

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