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PMID: 19448633 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys.

Nature medicine ·Vol. 15 ·No. 8 ·2009-08-00 ·Pages 901-6

Johnson PR, Schnepp BC, Zhang J, Connell MJ, Greene SM, Yuste E, Desrosiers RC, Clark KR

Abstract

The key to an effective HIV vaccine is development of an immunogen that elicits persisting antibodies with broad neutralizing activity against field strains of the virus. Unfortunately, very little progress has been made in finding or designing such immunogens. Using the simian immunodeficiency virus (SIV) model, we have taken a markedly different approach: delivery to muscle of an adeno-associated virus gene transfer vector expressing antibodies or antibody-like immunoadhesins having predetermined SIV specificity. With this approach, SIV-specific molecules are endogenously synthesized in myofibers and passively distributed to the circulatory system. Using such an approach in monkeys, we have now generated long-lasting neutralizing activity in serum and have observed complete protection against intravenous challenge with virulent SIV. In essence, this strategy bypasses the adaptive immune system and holds considerable promise as a unique approach to an effective HIV vaccine.

MeSH Terms
Animals Antibodies, Viral/immunology,metabolism CD4 Immunoadhesins/immunology Gene Transfer Techniques/veterinary Genetic Vectors/immunology Haplorhini/genetics,immunology Immunotherapy/methods,veterinary Models, Biological Neutralization Tests SAIDS Vaccines/genetics,therapeutic use Simian Acquired Immunodeficiency Syndrome/blood,immunology,prevention & control Simian Immunodeficiency Virus/immunology Treatment Outcome
Chemicals
Antibodies, Viral CD4 Immunoadhesins SAIDS Vaccines
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Johnson Philip R
The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. johnsonphi@chop.edu
Schnepp Bruce C
Zhang Jianchao
Connell Mary J
Greene Sean M
Yuste Eloisa
Desrosiers Ronald C
Clark K Reed
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.1967
Email
johnsonphi@chop.edu
Published
2009-08-00
Epub
2009-00-17
Pages
901-6
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC2723177
Subset
IM
Grants
NIAID NIH HHS · P01 AI026507 · United States
NIAID NIH HHS · P01 AI026507-100005 · United States
Corrections
CommentIn
PMID: 19661984
External Links
PubMed source DOI: 10.1038/nm.1967 PMC Full Text View journal details
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