Pushing the Envelope

Study provides a new strategy for HIV vaccine development

Image: J. Roberto Trujillo/Wikimedia Commons

Image: J. Roberto Trujillo/Wikimedia Commons

A new study led by scientists at Harvard Medical School and Beth Israel Deaconess Medical Center demonstrates that a heterologous prime-boost HIV-1 vaccine regimen protected 50 percent of vaccinated nonhuman primates against challenges with the simian immunodeficiency virus (SIV), a virus similar to HIV that infects nonhuman primates. Published in the July 2 online edition of Science, these new findings provide a new strategy for the clinical development of this novel HIV-1 vaccine candidate.

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“Despite the urgent need for a safe and effective global HIV-1 vaccine, only four vaccine concepts have been evaluated for protective efficacy in humans over the past 30 years,” said lead author Dan Barouch, HMS professor of medicine and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess. “We are very encouraged by the results of this latest preclinical HIV-1 vaccine study and believe the findings may lead to a clear path forward for evaluating this HIV vaccine candidate in humans.”

In this work, nonhuman primates were first given a dose of adenovirus serotype 26 vectored vaccine to “prime” the immune system to mount an antibody response and then received a “boost” with a purified HIV envelope protein (the surface protein of HIV), which enhances the immune system over time. (Adenovirus 26 is responsible for the common cold and is engineered to serve as a carrier, or vector, to deliver pieces of SIV into cells.)

The study results showed that the prime-boost vaccine regimen provided complete protection in half of the vaccinated nonhuman primates against a series of six repeated challenges with SIV.

“Our previous studies of viral vector-based HIV-1 vaccine candidates showed much lower levels of protection against SIV,” said Barouch. “These new findings show that the envelope protein boost following the viral vector priming increases the magnitude and functionality of antibody responses and improves protection.”

Based on these preclinical data, the HIV-1 version of this vaccine regimen is now being evaluated in an ongoing international clinical study sponsored by Crucell Holland BV, one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

More than 35 million people worldwide are infected with HIV and more than 2 million new infections develop each year. “Although antiretroviral therapies have prolonged the lives of HIV-1 infected patients, the definitive solution to this epidemic will likely be a vaccine,” said Barouch. “These new findings represent an important step forward.”

The study was supported by the following grants from the National Institutes of Health: AI060354; AI078526; AI0080280; AI084794; AI095985; AI096040; AI102660; AI102691; OD011170; HHSN261200300001E, as well as funding from the Bill & Melinda Gates Foundation and the Ragon Institute.

Adapted from a Beth Israel Deaconess news release.