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RFA grad involved in search for Zika virus vaccine

Nicole A. Hawley
Posted 2/12/16

A Rome native who just more than a year ago was part of a group of researchers who received a three-year multi-million dollar grant to develop a vaccine for dengue fever is now working to find one …

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RFA grad involved in search for Zika virus vaccine

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A Rome native who just more than a year ago was part of a group of researchers who received a three-year multi-million dollar grant to develop a vaccine for dengue fever is now working to find one for the Zika virus.

Dr. Sean Diehl, a 1994 graduate of Rome Free Academy, works for the University of Vermont Vaccine Testing Center, which will be involved in the clinical trials and research on a vaccine for Zika virus, which was declared a global health emergency by the World Health Organization on Feb. 1.

Zika virus is a mosquito-borne flavivirus closely related to dengue virus. It was first isolated from a rhesus monkey in Zika forest, Uganda in 1947, in mosquitoes in the same forest in 1948 and in humans in Nigeria in 1954. Zika virus is endemic in parts of Africa and Asia and was first identified in the South Pacific after an outbreak on Yap Island in the Federated States of Micronesia in 2007. 

Zika virus is primarily transmitted to humans through bites from Aedes mosquitoes, which often live around buildings in urban areas and are usually active during daylight hours. Peak biting activity occurs in early mornings and late afternoons.

Some evidence suggests Zika virus can also be transmitted to humans through blood transfusion, perinatal transmission and sexual transmission. However, these modes are very rare, according to WHO.

The Centers for Disease Control and Prevention confirmed a link between Zika and the birth defect in which babies are born with abnormally small heads.

On Jan. 22, the CDC activated its Emergency Operations Center to respond to outbreaks of Zika occurring in the Americas and increased reports of birth defects and Guillain-Barré syndrome in areas affected by Zika. On Feb. 1, the WHO declared a Public Health Emergency of International Concern (PHEIC) because of clusters of microcephaly and other neurological disorders in some areas affected by Zika. On Feb. 8, CDC elevated its EOC activation to a Level 1, the highest level.

UVM Vaccine Testing Center faculty Dr. Kristen Pierce, an infectious disease specialist and associate professor of medicine, and Dr. Diehl, an immunologist and assistant professor of medicine, have expertise in the characteristics of flaviviruses – a group of viruses, mostly transmitted via insects, that cause such human diseases as Zika virus, yellow fever, dengue, various types of encephalitis, and hepatitis C – and related vaccines.

Diehl studies the basic mechanisms of flaviviruses, vaccines against flaviviruses, and the immune responses triggered by flavivirus natural infection or vaccination. 

Recently Diehl answered questions about the work his team will conduct on developing a vaccine for Zika.

Q: How and/or why were you selected to be on this team at UVM? Was it the result of your work toward a vaccine for dengue fever?

Diehl: The University of Vermont Testing Research Center been working since 2009 with the National Institutes of Health to develop vaccines for dengue fever and for West Nile virus. These, like Zika virus, are both flaviviruses and therefore have a similar genetic structure, so we will use the platform for dengue vaccine development for the Zika vaccine.

My specific role at the University of Vermont is assistant professor of Medicine-Infectious Disease. At the Vaccine Testing Center I am associate director of research. My specialty is the immune system. Our mission is not only to further vaccine candidates and models of human infection through clinical development, but also to understand how these vaccines and infections engage the immune system to offer long-term protection. 

Q: Can you describe what kind of work you’ll be doing and is there any anticipated timeline for when a vaccine could be developed?

Diehl: Our collaborator at the NIH (see below) is developing a Zika virus vaccine based on the dengue technology. Essentially this involves growing the virus that has infected a patient, isolating the genetic material and making modifications to it designed to weaken the virus. This genetic material is then inserted into a virus-producer cell in the lab to make a modified (that is to say, attenuated) virus that is secreted by these cells into the cell culture liquid.

This virus is then verified to be weakened. The weakened virus is first tested in animal models and if deemed safe in those models, an application is made to the Federal Drug Administration for an Investigational New Drug. Once that occurs, a very high quality virus is made for use in clinical trials.

At UVM and Johns Hopkins, we apply for approval with our institutional review board who needs to approve studies involving humans. Once approved we then recruit subjects, inform them on all aspects of the study, perform pre-screening and once enrolled, we administer the vaccine. Subjects are closely monitored for safety through clinical visits and laboratory results and we measure the immune response to the vaccine over time. We anticipate being able to start recruiting subjects for this trial in the fall of 2016. 

Q: Any other specialists from other universities or countries that you’ll be working with?

Diehl: We will be working closely with Dr. Anna Durbin and her team at the Center for Immunization Research at Johns Hopkins School of Public Health and also with Dr. Stephen Whitehead, of the Laboratory of Infectious Diseases at the NIH. Dr Whitehead is spearheading the laboratory development of the actual Zika vaccine. In parallel with Johns Hopkins, we will be administering the top Zika vaccine candidate to healthy subjects at our sites in Burlington, Vt. and Baltimore, Md., respectively.

My specific role in the process will be overseeing the tests of the immune response to the vaccine including both antibody responses and cellular immune responses. 

Q: What similarities or differences will there be in your work developing this vaccine as opposed to the dengue fever vaccine?  What is perhaps more challenging?

Diehl: In a way this vaccine is simpler in composition than the dengue vaccine, but also more unknown at the same time.

Simpler because there is only one “type” of Zika virus whereas there are four different types of dengue that need to be combined into a single vaccine.

Although historically symptoms from Zika appear to be milder than dengue, much less is known about Zika virus in the literature. This is especially true in terms of how immunity to dengue might interact with Zika and vice-versa, and this will be the biggest challenge to determining how much of the immune response to the Zika vaccine cross reacts with dengue viruses and vice versa.

With our experience in dengue vaccination we are well prepared to develop new specific tests for Zika and meet the challenge of working towards a Zika vaccine.

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