ABSTRACT The global spread of the human immunodeficiency virus (HIV) has intensified efforts to develop an effective vaccine. A significant obstacle to such an effort is the remarkably high mutation rate of HIV. This high mutation rate is most evident in the envelope (Env) coat protein, the target of neutralizing antibody activity. Most vaccine candidates tested to date have utilized a single Env protein. Such vaccines have been shown to protect non-human primates from immunodeficiency viruses provided that the vaccine and challenge viruses were matched for Env sequences. However, when heterogeneous virus stocks were used for challenge in these studies, protection was incomplete. Similarly, when single-Env HIV vaccines were tested in clinical trials, protection was incomplete in that some vaccines were subsequently infected with HIV. This was likely, in part, because the narrow, type-specific responses elicited by single-Env vaccines could not block infections by unrelated field isolates. Our strategy differs from others, as we have designed poly-Env vaccines, with a goal to protect against diverse HIV. Env protein have been isolated, characterized, and tested in the context of single and mixed vaccines. Vaccine studies have progressed from tests in small animals to tests in non-human primates, and to phase I clinical trials.
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