Miller School Researchers Making Major Strides Against Zika Virus

Monoclonal antibodies may be the key to developing a treatment for the Zika virus, according to researchers at the University of Miami Miller School of Medicine who are collaborating with other infectious disease specialists in Brazil and the United States.

Speaking at the Miller School’s “Zika Forum: State of the Science, Public Health Safety and Ethics,” Mario Stevenson, Ph.D., professor of medicine and Chief of Infectious Diseases, said, “We have a formidable team of virologists here who are up to the task of taking appropriate action against the virus.”

More than 300 researchers, clinicians, public health officials and students attended the March 23 conference to share the latest findings about the virus and discuss related ethical issues.

“This is an opportunity for us to learn from each other about the impact of the Zika virus on humans, the extent of the epidemic and how to defeat the virus by scientific methods,” said Pascal J. Goldschmidt, M.D., Dean of the Miller School, in a welcome to attendees.

David I. Watkins, Ph.D., professor and Vice Chair for Research in the Department of Pathology, outlined his collaborative work with Esper G. Kallas, M.D., Ph.D., an infectious disease specialist and professor of medicine at the University of São Paulo, Brazil, building on an approach used against other tropical viruses.

“Understanding the history of these viruses provides a direction for the future,” said Watkins. “Two measures were successful in the Ebola outbreak in western Africa. The first was a VSP vaccine and the second was the treatment with a cocktail of monoclonal antibodies for individuals who are already infected. This is the route we have chosen to take in developing anti-Zika treatments.”

The Zika virus is believed to be causing microcephaly, a birth defect in which a baby is born with an abnormally small head because of severe infection of the fetus’s brain, when it infects pregnant women. The virus is primarily transmitted by the Aedes aegypti mosquito, although cases of infection through sexual intercourse have also been reported.

Watkins has been working with Kallas, who was the keynote speaker at the forum, to develop a monoclonal antibody against Zika.

“Our goal is to produce an antibody that can live for six to nine months in concentrations high enough to neutralize the virus,” he said, adding that monoclonal antibodies given to pregnant women can usually pass through the placenta and provide a similar level of protection to the fetus.

Kallas has extracted plasmablasts — immature plasma cells in the blood that produce antibodies — from four Zika-infected patients.

“We can copy, manufacture and test these antibodies to see if they will neutralize or kill the virus,” Watkins said. “We have already assessed the first 18 monoclonal antibodies at the Miller School and have found one that will neutralize the Zika virus. The next step is seeing if we can prevent a Zika infection in rhesus macaques. If successful, we would then produce the antibodies in large amounts and test them for safety and efficacy in humans.”

Miller School virologist Ronald Desrosiers, M.D., Ph.D., professor of pathology, is working with Watkins and Kallas to develop potent neutralizing antibodies. “One of the promising approaches is to use an adeno-associated virus (AAV) vector to deliver antibodies to the muscle cells, which then turn into factories producing the protective antibodies against Zika over decades,” he said.

Glen N. Barber, Ph.D., Professor and Chair of the Department of Cell Biology, is studying how to design a vaccine that could protect against Zika infection. Rather than using an attenuated live virus for vaccinations — an approach used for decades with other diseases — a Zika vaccine would incorporate only certain components of the virus for patient safety, Barber said.

“We have been looking at the protein envelope of the virus to see if that stimulates a robust response from the immune system,” he said. “We have made significant strides in the last few months, and plan to test this approach with macaques in the near future. The good news is that the variations in the virus are very small, so immunizing against one strain should protect against the others. ”

Raymond F. Schinazi, Ph.D., the Frances Winship Walters Professor of Pediatrics, Director of the Laboratory of Biochemical Pharmacology, and Director of the Scientific Working Group on HIV Reservoirs and Viral Eradication at Emory University, noted that the genetic components of the three reported strains of Zika — South American, West African and Asian — are 96 to 98 percent similar. That would make it easier to develop a vaccine, he said in a keynote address.

“But we need to learn more about the Zika virus,” he added. “For instance, is it the virus or the way it interacts with the nerve cells or the immune system that is important?”

Infectious disease specialist Rafael E. Campo, M.D., professor of clinical medicine, led a panel discussion on “Symptoms, Treatment and Health Implications from Zika Virus Infection.”

Panelist Thomas Hooton, M.D., professor of clinical medicine and Medical Director of UHealth Infection Control, said the Zika virus affects all age groups, although symptoms typically resolve in a few days.

“Fever, rashes and joint pain can be a symptom of Zika, but also influenza or other tropical diseases,” he said. “You have to consider the entire context from a clinical standpoint.”

Micheline McCarthy, M.D., Ph.D., professor of neurology, added that Zika, like other tropical viruses, can affect the nervous system and produce symptoms resembling Guillain Barre Syndrome.

“Fortunately, this condition of progressive body weakness is generally reversible with good care,” she said.

Christine L. Curry, M.D., Ph.D., assistant professor of obstetrics and gynecology, said she counsels many women who are pregnant or considering pregnancy.

“We typically advise them to follow the recommendations from the CDC (U.S. Centers for Disease Control and Prevention),” she said. “But when it comes to the big question. ‘What is the likelihood of a problem?’ we have to say, ‘I don’t know,’ at this point.”

Jose Szapocznik, Ph.D., Professor and Chair of the Department of Public Health Sciences, moderated a panel discussion on controlling the mosquitoes that spread the Zika virus in tropical and subtropical regions. In Brazil alone, the number of confirmed cases of microcephaly was 907 on the day of the forum, and another 4,200 possible cases were being investigated.

“We’re very concerned about the Zika virus,” said John Beier, Sc.D., professor of public health sciences and Director of the Division of Environmental and Public Health. He called the Aedes aegypti a challenge for vector biologists to control, noting that the mosquito — which can also transmit yellow fever, dengue fever and the chikungunya virus — has even demonstrated an ability to go underground and find suitable habitats during winter.

Florida has some of the world’s most effective mosquito control methods, Beier said. But in developing countries, mosquito infestations can be difficult to control, allowing the vector-borne diseases to spread easily. Giving people better access to safe drinking water and improving sewage treatment practices could help, he said.

A gallery of photos from the event can be found here.

University of Miami faculty, students and staff who were unable to attend the Forum on March 23 can watch a video recording online. Instructions to access the video through UM’s Blackboard System can be found here.

The forum was presented by the Miller School, the Division of Infectious Diseases, the Department of Public Health Sciences and UHealth – the University of Miami Health System, in partnership with the Miller School’s Institute for Bioethics and Health Policy, Institute of AIDS and Emerging Infectious Diseases, International Medicine Institute, University of Miami Clinical and Translational Science Institute, and the Florida Department of Health in Miami-Dade.

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