Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope

Author:

Arnold Gail Ferstandig123,Velasco Paola K.123,Holmes Andrew K.123,Wrin Terri4,Geisler Sheila C.12,Phung Pham4,Tian Yu2,Resnick Dawn A.12,Ma Xuejun12,Mariano Thomas M.12,Petropoulos Christos J.4,Taylor John W.2,Katinger Hermann5,Arnold Eddy123

Affiliation:

1. Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey

2. Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey

3. Rutgers University—University of Medicine and Dentistry of New Jersey Molecular Biosciences Graduate Program, Piscataway, New Jersey

4. Monogram Biosciences, Inc., South San Francisco, California

5. Institute of Applied Microbiology, University of Agriculture, Vienna, Austria

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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