Many MHRP researchers have shifted their attention to COVID-19 during the current global health emergency. WRAIR’s Emerging Infectious Diseases Branch (EIDB), led by Dr. Kayvon Modjarrad, is leading efforts to develop a safe and effective vaccine to prevent infection with COVID-19. WRAIR’s vaccine, called the Severe Acute Respiratory Syndrome Coronavirus-2 Spike Ferritin Nanoparticle (SpFN), is one of many currently in development.
MHRP's Dr. Rolland and her team recently characterized SARS-CoV-2 coronavirus diversification since the beginning of the pandemic and found that the SARS-CoV-2 genome has evolved through a mostly random process rather than through adaptation to the human hosts it encounters. Given the low level of genetic variation, Dr. Rolland thinks that a promising vaccine candidate would likely be equally efficacious against all currently circulating variants of the COVID-19 coronavirus.
ALFQ, develop at MHRP, will be used in the SpFN vaccine formulation, and many MHRP scientists are supporting pre-clinical studies of the vaccine candidate.
In 2012, the National Institute on Drug Abuse (NIDA) of the National Institutes of Health awarded a $5 million grant to MHRP scientists led by Dr. Gary Matyas to support the research and development of a heroin vaccine. The ultimate goal is to combine this experimental vaccine with a safe, effective HIV vaccine to concurrently address the entwined epidemics of heroin abuse and HIV and provide considerable public health benefit.
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 worked with a team at NIDA to develop a vaccine that induces antibodies that bind to the drug in the bloodstream, preventing the drug from reaching the brain.
The collaboration began in 2010, and built upon previous preclinical research indicating that hapten-based anti-drug vaccines—in which a small molecule chemically similar to a drug of abuse (hapten) is bound to a protein carrier to induce an immune response—showed promise against a variety of abused drugs, including heroin.
In preclinical studies, the candidate heroin vaccine-induced antibodies that prevented heroin from crossing the blood-brain barrier in mice and rats for a period of up to three months. Results were published in the Journal of Medicinal Chemistry. By binding heroin in the blood and thus reducing its passage into the brain, the vaccine aims to block the euphoria and addictive effects of heroin and other commonly misused opioids.
Researchers at MHRP and partners at SUNY Upstate Medical University in Syracuse, N.Y., were awarded a grant in 2018 to advance the experimental heroin vaccine through Phase 1/2a clinical trials to assess both its safety and its efficacy against a morphine challenge.
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.
Gp145 is slated as a boost in the upcoming RV460 trial slated to begin in Kenya in 2021. It will be a randomized, double blind comparative adjuvant study for a DNA/protein prime/boost HIV vaccine. One of the adjuvants being evaluated in this study is the MHRP-created ALF product.