1. Fusion-competent vaccines: broad neutralization of primary isolates of HIV.
- Author
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LaCasse RA, Follis KE, Trahey M, Scarborough JD, Littman DR, and Nunberg JH
- Subjects
- Animals, CD4 Antigens metabolism, Cell Fusion, Coculture Techniques, Epitopes immunology, Gene Products, env chemistry, Gene Products, env metabolism, Giant Cells, HIV Antibodies biosynthesis, HIV Antigens chemistry, HIV Envelope Protein gp120 chemistry, HIV Envelope Protein gp120 immunology, HIV Envelope Protein gp120 metabolism, HIV Envelope Protein gp41 chemistry, HIV Envelope Protein gp41 immunology, HIV Envelope Protein gp41 metabolism, HIV Infections virology, HIV-1 isolation & purification, HIV-1 physiology, Humans, Mice, Mice, Transgenic, Neutralization Tests, Protein Conformation, Receptors, CCR5 metabolism, Tumor Cells, Cultured, AIDS Vaccines immunology, Gene Products, env immunology, HIV Antibodies immunology, HIV Antigens immunology, HIV-1 immunology
- Abstract
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.
- Published
- 1999
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