UM SOM is Center Stage in Testing National Institutes of Health Zika Vaccine

UM SOM'S Center for Vaccine Development, Tapped Previously for Ebola Vaccine, Now Steps Up to Help Test NIH-Developed Zika Vaccine

As world leaders increasingly recognize the Zika virus as an international public health threat, the Center for Vaccine Development (CVD) at the University of Maryland School of Medicine's Institute for Global Health (IGH) has been chosen as one of three study sites in a human safety trial of a new Zika vaccine. The early-stage study will evaluate the experimental vaccine's safety and ability to generate an immune system response in participants.

The selection of the University of Maryland School of Medicine (UM SOM) marks the second time in two years that the School's internationally-acclaimed CVD has been tapped to assist in vaccine testing efforts amidst a growing crisis. In 2014, the UM SOM was the only U.S. medical school asked to join an unprecedented international consortium formed by the World Health Organization. The Consortium resulted in the evaluation of one of the first experimental Ebola vaccines (ChAd3-EBO-Z), developed by the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID). Recently, the CVD received FDA approval for the first vaccine approved in the U.S. for protection against Cholera. In July, the CVD began malaria vaccine trials in Burkina Faso.

The Zika vaccine trial, which will involve at least at least 80 volunteers at three sites in the United States, is being undertaken by NIAID, part of the National Institutes of Health (NIH). The early-stage study will evaluate the experimental vaccine's safety and ability to generate an immune system response against Zika.

Scientists at NIAID's VRC developed the investigational vaccine—called the NIAID Zika virus investigational DNA vaccine—earlier this year.

The Principal Investigator on the study is Monica A. McArthur, MD, PhD, Assistant Professor, Department of Pediatrics at the UM SOM, whose primary research interests are the interactions between pathogens and the human immune system.

"As we learn more about the threat that Zika poses, and as it spreads further and further, the need for a vaccine becomes greater," said Kathleen Neuzil, MD, MPH, CVD Director, Professor of Medicine, and Deputy Director of IGH "The CVD welcomes the opportunity to collaborate with the NIH on this extremely important effort."

The study is part of the U.S. government response to the ongoing outbreak of Zika virus in the Americas. According to the Centers for Disease Control and Prevention, more than 50 countries and territories have active Zika virus transmission. In the United States and its territories, more than 6,400 Zika cases have been reported. Although Zika infections are usually asymptomatic, some people experience mild illness lasting about a week. However, Zika virus infection during pregnancy can cause a serious birth defect called microcephaly, as well as other severe fetal defects of the brain and other organs. There are no vaccines or specific therapeutics to prevent or treat Zika virus disease.

The NIAID Zika virus investigational DNA vaccine approach is similar to that used for another investigational vaccine developed by NIAID for West Nile virus. That vaccine candidate was found to be safe and induced an immune response when tested in a Phase 1 clinical trial.

The investigational Zika vaccine includes a small, circular piece of DNA—called a plasmid—that scientists engineered to contain genes that code for proteins of the Zika virus. When the vaccine is injected into the arm muscle, cells read the genes and make Zika virus proteins, which self-assemble into virus-like particles. The body mounts an immune response to these particles, including neutralizing antibodies and T cells. DNA vaccines do not contain infectious material—so they cannot cause a vaccinated individual to become infected with Zika—and have been shown to be safe in previous clinical trials for other diseases.

"A team of scientists here at NIAID worked tirelessly to rapidly develop this vaccine for clinical testing," said John Mascola, MD, director of NIAID's VRC. "DNA or gene-based vaccines induce antibodies, but they also can activate the cell-mediated immune response, which ultimately could yield strong and durable protection against disease."

The Phase 1 clinical trial, called VRC 319, is led by Julie E. Ledgerwood, D.O., chief of the VRC's clinical trials program. Volunteers will be divided randomly into four study groups of 20 people each. After enrollment, all participants will receive a vaccination at their first visit via a needle-free injector that pushes the vaccine fluid into the arm muscle. Half of the participants will receive one additional vaccination eight weeks or 12 weeks later. The remaining participants will receive two additional vaccinations: one group of 20 participants will receive a second vaccine at week four and a third at week eight; the other group of 20 participants will receive a second vaccine at week four and a third at week 20. All participants will receive the same dose at each vaccination.

Following each vaccination, participants will remain at the study site for observation for a minimum of 30 minutes so clinicians can monitor for any adverse reactions. Participants will receive a diary card to use at home to record their temperature and any symptoms for seven days following each vaccination.

All participants will return for follow-up visits within a 44-week time period after the first vaccination so investigators can monitor their health to determine if the vaccine is safe. The study team will review patient data daily and weekly to monitor safety. A Protocol Safety Review Team will also conduct formal interim safety reviews.

At follow-up visits, investigators will also take blood samples for laboratory testing to measure the immune response to the vaccine. Participants will be asked to return for two follow-up visits at 18 months and two years following the initial vaccination so investigators can obtain additional blood samples to assess the durability of the immune response.

The other two study sites are Emory University in Atlanta and NIH in Bethesda, Maryland. Initial safety and immunogenicity data from the Phase 1 trial are expected by the end of 2016. If results show a favorable safety profile and immune response, NIAID plans to initiate a Phase 2 trial in Zika-endemic countries in early 2017.

"Zika is an urgent international public health threat, including, now, in parts of our own country," said UM SOM Dean E. Albert Reece, MD, PhD, MBA, who is also vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor. "It is gratifying to see the University of Maryland School of Medicine's Center for Vaccine Development continue to be involved on the front lines of addressing these global threats, as we have done with Ebola and other infectious diseases."

About the University of Maryland School of Medicine

The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States and continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland's Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in brain science, cancer, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. http://medschool.umaryland.edu/

About the UM SOM CVD

The CVD, which was founded by Dr. Myron "Mike" Levine in 1974, is one of the most recognized entities for developing, testing, and implementing vaccines in the world. Within the IGH, the CVD develops and tests vaccines to prevent infectious diseases that disproportionately affect people living in the least developed countries.   For the past 40 years, the CVD has conducted a wide range of research relating to the development of vaccines for a variety of diseases, including cholera, typhoid fever, paratyphoid fever, non-typhoidal Salmonella disease, shigellosis, Escherichia coli diarrhea, malaria, and other infectious diseases, including influenza. The CVD also developed new delivery systems, as well as public health and vaccine policy around the world, including Africa, Asia, and Latin America. Most recently, researchers at the CVD received worldwide attention for leading CVD's direct involvement in the WHO's global consortium for accelerated testing of a new Ebola vaccine candidate in Mali and Baltimore.