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Other Vaccine Candidates
In August 2015, MHRP sites in Uganda and Thailand initiated a Phase II study of an HIV vaccine candidate that uses Ad26 prime with an MVA and protein boost.
The inserts of this vaccine are mosaic constructs and the protein boost is subtype C. Although the protein is subtype-specific, the mosaic inserts are intended to provide broad response so the final vaccine can be deployed globally.
The study, called A004, is the critical path study to down-select for a final regimen to advance to efficacy testing. In addition to contributing sites and collaboratively designing the study and development plans, MHRP provides the MVA being tested in A004. The study is funded and sponsored by Janssen, a division of J&J.
In 2012, the National Institute on Drug Abuse awarded a $5 million grant to MHRP scientists to support the research and development of a combination heroin/HIV vaccine. This innovative dual-vaccine model would concurrently address the entwined epidemics of heroin abuse and HIV and could provide considerable public health benefit.
Since the onset of the HIV epidemic, scientists and public health advocates have attempted to curb the high prevalence of HIV among intravenous drug users. Heroin addicts in particular have a higher rate of HIV infection.
Originally developed as a pain reliever, heroin easily flows past the blood-brain barrier and evokes a powerful sense of euphoria and relief. Leveraging MHRP’s novel adjuvants research, scientists are working on developing a vaccine that induces antibodies that bind to the drug in the bloodstream, preventing the drug from crossing the blood-brain barrier, and blocking the euphoria and addictive effects.
Because heroin is too small a molecule to induce antibodies on its own, researchers work closely with organic chemists to create the structural analog (hapten) that is joined to a carrier protein and used in the vaccine. Future studies will combine the heroin and HIV vaccines, to tackle both the cause and effects of addiction to the drug.
Principal Investigator: Gary Matyas, Ph.D
Following an investment from the National Institute of Allergy and Infectious Diseases (NIAID), a unique HIV vaccine candidate developed by MHRP scientists in collaboration with Advanced BioScience laboratories will be produced for potential use in clinical studies.
The move to further test the new protein boost vaccine candidate—a subtype C gp145 Env subunit vaccine—came about after the success of the MHRP-led RV144 trial renewed interest in this type of vaccine. RV144 showed V2 antibodies (a type of antibody also elicited by gp145), correlated with a lower risk of HIV infection. In the RV144 trial, a subunit protein boost was similarly used to effectively generate antibodies.
The research team, led by MHRP’s Dr. Vicky Polonis, based the gp145 subunit vaccine on HIV subtype C, which represents more than 50% of global HIV infections. In addition to its prevalence, several studies have shown unique properties of C envelopes, or the outer coat of the virus, including rapid and potent antibody elicitation. These properties make the subtype C gp145 an attractive vaccine candidate.