Broad neutralization of human immunodeficiency virus type 1 (HIV-1) elicited from human rhinoviruses that display the HIV-1 gp41 ELDKWA epitope.
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.
Arnold
Gail Ferstandig
GF
Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA. gfarnold@cabm.rutgers.edu
Velasco
Paola K
PK
Holmes
Andrew K
AK
Wrin
Terri
T
Geisler
Sheila C
SC
Phung
Pham
P
Tian
Yu
Y
Resnick
Dawn A
DA
Ma
Xuejun
X
Mariano
Thomas M
TM
Petropoulos
Christos J
CJ
Taylor
John W
JW
Katinger
Hermann
H
Arnold
Eddy
E
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D009500:Neutralization Tests; D019151:Peptide Library; D015202:Protein Engineering; D012229:Rhinovirus / Q000235:genetics
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D019151:Peptide Library; C514787:gp41 protein, Human immunodeficiency virus 1