• STAT News
• By:  Andrew Joseph @DrewQJoseph

Two new experimental vaccines protect mice against the Zika virus, a study out Tuesday shows.

Researchers from governments, academic labs, and biopharma companies have been rushing to develop Zika vaccines since global health experts started warningabout the previously unknown dangers wrought by the mosquito-borne virus,  including serious birth defects. Just last week, the Food and Drug Administration approved the first human testing of a Zika vaccine candidate from the company Inovio Pharmaceuticals.

For the new study, which was published in the journal Nature, scientists tested two kinds of vaccine on mice — one made from DNA and one from an inactivated form of the virus. With one dose, both vaccines prompted the creation of antibodies that shielded the animals from becoming infected when they were exposed to the virus.

“The protection was striking,” said senior author Dr. Dan Barouch, the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston.

Just because the vaccines worked in mice does not mean they will work in people. And even if the vaccines are ultimately successful, they still have to be tested in other animals and small groups of people before they could be deployed widely. Complicating the challenge is that the main goal of any vaccine will be to protect pregnant women — so the inoculation will have to pass rigorous safety tests.

The US Army developed the vaccine made from the inactivated virus and hopes to start testing it in people later this year, said Col. Nelson Michael, an author on the Nature paper and director of the US Military HIV Research Program at Walter Reed Army Institute of Research. Michael said the research group was partnering with a pharmaceutical company to advance the vaccine through clinical development, but would not yet disclose which company.

Inovio’s vaccine is a DNA vaccine, as is a fourth vaccine being designed by the National Institute of Allergy and Infectious Diseases. In those vaccines, patients would receive DNA that produces a protective protein.

The vaccines presented in Tuesday’s paper provided at least two months of immunity in the mice, researchers said. They are exploring if and how that could be extended and are also conducting experiments in pregnant animals. Barouch did not offer a timeline for when the scientists hope to start testing the DNA vaccine in people.

The researchers also need to tease apart if and how well the vaccine would function in patients with existing antibodies from a former dengue infection, Barouch said. Dengue, a related mosquito-borne virus, previously swept through much of the same territory Zika is now moving through, and some scientists have speculated a prior dengue infection could make the impact of Zika worse.

BIDMC, OHSU to Lead Consortium Exploring Vaccine Candidate and Cure Strategies

• BIDMC Contact: Jennifer Kritz
• Phone: 617-667-7301
• Email: jkritz@bidmc.harvard.edu
• Boston Magazine

BOSTON – With $42 million in funding from the National Institutes of Health, scientists from Beth Israel Deaconess Medical Center (BIDMC) and Oregon Health & Science University (OHSU) will lead a five-year research initiative to advance efforts to cure and prevent HIV/AIDS.  Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC, and Louis Picker, MD, Assistant Director of the OHSU Vaccine and Gene Therapy Institute, will lead a consortium of researchers from across the country exploring the mechanisms behind promising new HIV vaccine candidates and potential cure strategies.

More than 35 million people worldwide are infected with HIV, and more than 2 million new infections develop each year. “Antiretroviral therapies have allowed people infected with HIV to lead longer, healthier lives, but a vaccine and a definitive cure for infection would accelerate an end to this global epidemic,” said Barouch, who is also Professor of Medicine at Harvard Medical School.

The researchers will focus their work in two key areas: 1) understanding the mechanisms of why the current preventive HIV vaccines developed by Barouch and Picker are providing protection from infection in nonhuman primates; and 2) building on that knowledge to create both an effective preventive and therapeutic (cure) HIV vaccine.

“This grant gives us the opportunity to more closely collaborate with other scientists around the country who have a common goal: to end the HIV epidemic,” said Picker, who is also a Professor of Pathology/Molecular Microbiology and Immunology in the OHSU School of Medicine. “Stopping HIV may require a combination of vaccine approaches to get to full protection. There are just a handful of promising vaccine platforms out there, and if we can better understand why they are working, we’ll have a better shot at getting to the next generation of therapeutic vaccines that could cure current HIV infections.”

Barouch will lead a group of scientists from BIDMC and other institutions to define how candidate HIV vaccines may be able to protect against infection. They will study an adenovirus serotype 26 vectored vaccine with a purified HIV envelope protein (the surface protein of the HIV virus), which enhances the immune responses. This vaccine candidate was developed by Barouch and colleagues at BIDMC and is currently in international Phase 2a clinical trials.

In 2015, Barouch was lead author on a study in Science showing that a novel HIV vaccine using adenovirus serotype 26 (Ad26) regimen he and his research team developed at BIDMC provides robust protection against the virus in non-human primates. The study results showed that in half of the vaccinated non-human primates the prime-boost vaccine regimen provided complete protection against a series of six repeated challenges with the simian immunodeficiency virus (SIV), a virus similar to HIV that occurs in nonhuman primates.

With this new federal funding, Barouch and colleagues will evaluate the types and functions of the antibodies and cell-mediated immune responses induced by this vaccine, which will lead to a deeper understanding of how this vaccine might be able to protect HIV-uninfected individuals and also whether this vaccine could be used in HIV-infected individuals to help control the virus in the long term.

“With this vaccine candidate already in Phase 2a clinical trials, the knowledge gained in this research program will be immediately applicable to the development of clinical interventions,” Barouch said.

Concurrently, Picker will lead a team of investigators from OHSU working to better understand the efficacy of their unique preventive vaccine that uses cytomegalovirus (CMV) as the vector and is heading to Phase 1 human clinical trials next year in Portland, Ore. Picker’s 2013 landmark discovery published in Natureshowed in nonhuman primates that OHSU’s preventive vaccine not only controlled and stopped SIV, the nonhuman primate form of HIV, from spreading, but also cleared the virus in 50% of the primates’ systems.

“What we know so far is that our preventive vaccine using the unique CMV vector is able to control and clear the virus in nonhuman primates, but we haven’t shown why it works. Once we have a better understanding of the mechanisms that are making the preventive vaccine effective, there’s a chance that we could also optimize our vaccine, along with others,” said Picker.

In addition to Barouch and Picker, grant funding from the National Institute of Allergy and Infectious Diseases (UM1 AI124377), part of the NIH, will also support the work of Galit Alter, PhD, Ragon Institute of MGH, MIT and Harvard; R. Paul Johnson, MD, Emory University; Dennis Burton, PhD, Scripps Research Institute; Jeff Lifson, MD, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Rafick Sekaly, PhD, Case Western Reserve University; and Wenjun Li, PhD, University of Massachusetts Medical School.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

About OHSU

Oregon Health & Science University is a nationally prominent research university and Oregon’s only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children’s Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university’s social mission. OHSU’s Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer’s disease and new treatments for Parkinson’s disease, multiple sclerosis and stroke. OHSU’s Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.

The Center for Virology and Vaccine Research launched a Volunteer Registry for adults interested in clinical trial participation on December 21st, 2015. The new CVVR Clinical Trials Unit established the Volunteer Registry in anticipation of CVVR clinical trials beginning this year at Beth Israel Deaconess Medical Center. These clinical trials will connect the CVVR lab bench where the research vaccines were developed to the research volunteer’s bedside where the vaccines will be administered, all under the roof of BIDMC. Research volunteers are essential to clinical trials. The Volunteer Registry brings together researchers and volunteers with the common goal of helping others live healthier lives. The purpose of the Volunteer Registry is to collect and maintain information that people voluntarily supply so they may be contacted by the CVVR Clinical Trials Unit about participating in future studies. To find out more information about the Volunteer Registry follow this link: http://cvvr.hms.harvard.edu/registry or to join the Volunteer Registry please call the Clinical Trials Unit at (617)-735-4610 or follow this link:   https://redcap.bidmc.harvard.edu/redcap/surveys/?s=MKTMD7NKLH.