Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable t o elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIVvaccine irnrnunogens 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

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... ty of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A t o E. Development of these fusion-dependent immunogens may lead t o a broadly effective HIV vaccine.