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Journal of Virology, May 2009, p. 5087-5100, Vol. 83, No. 10
0022-538X/09/$08.00+0 doi:10.1128/JVI.00184-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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Dawn A. Resnick,1,2
Xuejun Ma,1,2
Thomas M. Mariano,1,2
Christos J. Petropoulos,4
John W. Taylor,2
Hermann Katinger,5 and
Eddy Arnold1,2,3*
Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey,1 Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey,2 Rutgers University—University of Medicine and Dentistry of New Jersey Molecular Biosciences Graduate Program, Piscataway, New Jersey,3 Monogram Biosciences, Inc., South San Francisco, California,4 Institute of Applied Microbiology, University of Agriculture, Vienna, Austria5
Received 26 January 2009/ Accepted 23 February 2009
In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.
Published ahead of print on 11 March 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
Present address: Abbott Laboratories, Bedford, MA.
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