Vaccine Combo Demonstrates Protection Against HIV-like Virus in Monkey Study

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Administering a 2-part prime-boost vaccine prevented infection in half of a dozen rhesus monkeys repeatedly exposed to simian immunodeficiency virus (SIV), and antibody responses against viral envelope proteins appeared to be the key to protection, according to a study published in the July 2 advance edition of Science magazine.

Numerous studies over the course of the HIV/AIDS epidemic have evaluated a wide range of vaccine approaches, but most have produced disappointing results. The work continues, however, as many experts think that only a vaccine can control the global epidemic.

Dan Barouch from Beth Israel Deaconess Medical Center and colleagues evaluated the protective efficacy of a vaccine regimen consisting of a weakened adenovirus 26 (Ad26) vector primer expressing SIV Env, Gag, and Pol proteins, followed by a booster based on purified gp140 viral envelope glycoprotein.

They found that 50% of 12 vaccinated rhesus monkeys were protected against infection after 6 rectal exposures to the SIVmac251 virus, while all unvaccinated control animals became infected. Protective efficacy was shown to be correlated with functional Env-specific antibody responses.

"These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys," the study authors concluded.  

The safety and immunogenicity of a similar vaccine regimen is now being tested in healthy HIV-negative volunteers in an international Phase 1/2a clinical trial sponsored by Johnson & Johnson (HIV-V-A004/NCT02315703).

Below is an edited excerpt from a Beth Israel Deaconess press release describing the study and its findings.

Study Shows Novel HIV Vaccine Regimen Provides Robust Protection in Non-Human Primates

Encouraging results provide a new strategy for clinical development of novel HIV-1 vaccine candidate

Boston -- July 2, 2015 -- A new study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) demonstrates that a heterologous prime-boost HIV-1 vaccine regimen protected 50 percent of vaccinated non-human primates (NHPs) against challenges with the simian immunodeficiency virus (SIV), a virus similar to HIV that infects NHPs. Published today in the online edition of Science, these findings provide a new strategy for the clinical development of this novel HIV-1 vaccine candidate.

"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 H. Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC and Professor of Medicine at Harvard Medical School. "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, NHPs 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 the HIV virus), 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 NHPs against a series of six repeated challenges with the simian immunodeficiency virus.

"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 pre-clinical data, the HIV-1 version of this vaccine regimen is now being evaluated in an ongoing Phase 1/2a international clinical study sponsored by Crucell Holland B.V., 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."

7/3/15

Reference

DH Barouch, G Alter, T Broge, et al. Protective efficacy of adenovirus-protein vaccines against SIV challenges in rhesus monkeys. Science. July 2, 2015 (Epub ahead of print).

Other Sources

Beth Israel Deaconess Medical Center. Study Shows Novel HIV Vaccine Regimen Provides Robust Protection in Non-Human Primates. Press release. July 2, 2015.

Johnson & Johnson. Investigational HIV Vaccine Regimen Shows Encouraging Results in Non-Human Primates. Press release. July 2, 2015.