Fusion-competent vaccines: broad neutralization of primary isolates of HIV.
Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.
LaCasse
R A
RA
The Montana Biotechnology Center and Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
Follis
K E
KE
Trahey
M
M
Scarborough
J D
JD
Littman
D R
DR
Nunberg
J H
JH
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D018920:Coculture Techniques; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015726:Giant Cells; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019713:Receptors, CCR5