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The “STEP-Wise” Future of Adenovirus-Based HIV Vaccines

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The HIV pandemic continues to be a public health crisis with over 30 million people currently living with the disease and, depending on the estimate, another 2 - 2.8 million infected annually. The disappointing results of the first Phase II study of a highly immunogenic adenovirus-vectored vaccine, named the STEP trial, was a wake up call to both the clinical and preclinical HIV vaccine fields. A vaccine designed only to elicit T cells and including a single HIV gene insert, will not be sufficient to reduce transmission or lower viremia in people. Additionally, future use of adenovirus-based vectored vaccines needs to be carefully planned with respect to vector type, gene inserts, route of immunization and risk factors among subject volunteers. The initial observation of a transient, increased risk of infection in Ad5 seropositive, uncircumcised men who have sex with men (MSM) is still unexplained, and may yet be considered simply a random event. The vaccine field has not given up on adenoviruses and there is continued interest in pursuing these highly immunogenic vectors, either in combination approaches with DNA, use of rare serotypes with low seroprevalence, or those derived from simian origin. Finally, evaluation of replicating adenovirus vectors known to be capable of inducing potent cellular, humoral, and mucosal immunity will be vital to meeting our future goal of an effective HIV vaccine.

Keywords: Adenovirus vectors; HIV vaccines; STEP trial; T cells; mucosal immunity; non-neutralizing antibodies

Document Type: Research Article


Publication date: 2011-09-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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