Antibody-based Protection Against HIV Infection by Vectored ImmunoProphylaxis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11-30

AUTHORS

Alejandro B. Balazs, Joyce Chen, Christin M. Hong, Dinesh S. Rao, Lili Yang, David Baltimore

ABSTRACT

Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV. More... »

PAGES

81-84

Journal

TITLE

Nature

ISSUE

7379

VOLUME

481

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature10660

    DOI

    http://dx.doi.org/10.1038/nature10660

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1008035308

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22139420


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    105 similar epitopes
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    107 somatic mutations
    108 specialized adeno-associated virus vector
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