Corbett Continues Quest for Dengue Fever Vaccine

February 17, 2014
Kizzmekia Corbett

Kizzmekia Corbett

In a new series, the UNC School of Medicine profiles graduate students who conduct research in labs across the UNC School of Medicine. First up is Kizzmekia Corbett, who received an off-campus dissertation fellowship from the UNC Graduate School to travel to Sri Lanka. Corbett will collect blood samples to search for a specific antibody response to the dengue virus, a key step in creating a vaccine for the world’s most widespread mosquito-borne disease.

 

Name: Kizzmekia Corbett

Alias: Kizzy

Hometown: Hillsborough, N.C.

Education: Bachelor of Science in biological sciences, University of Maryland-Baltimore County, 2008; doctorate student in microbiology and immunology, UNC

Award: Off-Campus Dissertation Fellowship, UNC Graduate School

Dissertation: “Dissecting Human Antibody Responses to Dengue Virus Infection”

Mentor: Aravinda de Silva, professor of microbiology and immunology

Goal: Vaccine development

Extracurriculars: Representative, UNC Student Congress; Staff, Honor System Attorney General; Member, Science Policy Advocacy Group; Delegate, UNC System Association of Student Governments

Hobbies: Shopping, politics, family fun

History:

Corbett’s parents thought she might become a police detective. A curious kid, she’d pursue the answers to her many questions to the ends of the Internet. Her detective work in high school led her to love science experiments. While at Orange County High School, she earned a slot in a summer program to train as a junior researcher at UNC’s Kenan Labs. At this young age, she eyed a doctorate degree in some sort of science.

Undergraduate research:

While attending University of Maryland-Baltimore County (UMBC), Corbett studied respiratory syncytial virus, which most humans are repeatedly exposed to, though most never know so because human immune systems easily control it. But the virus can cause serious upper respiratory problems for infants and the elderly. Corbett wanted to study why vaccines haven’t worked against the virus; she did that as part of the NIH Undergraduate Scholarship Program from 2006 to 2009.

Why UNC:

After excelling at UMBC, Corbett applied to graduate schools across the country — Harvard, Johns Hopkins, Cal-Berkeley. She was invited to interview at each of those schools and others, but the interview weekend at UNC stood apart. “It was really organized,” she remembers. “UNC clearly cares about students; they were more interested in what they could do for students to further our careers than they were about what we could bring to their research factories. I think any student here at UNC will say the same thing.”

Why the de Silva lab:

At UNC, each incoming student in the Biological and Biomedical Sciences Program rotates between several labs during their first year to see which lab might be the best fit. Corbett knew she wanted to do microbiology and immunology. With her NIH experience, Aravinda de Silva’s lab seemed like the perfect fit due to his focus on global health and the dengue virus.

Why dengue fever:

It’s the most significant mosquito-borne viral disease in the world in terms of cost and health burden. The symptoms can get particularly nasty — high fever, severe pain, nausea and vomiting. In some cases there is internal bleeding, which can lead to a sudden drop in blood pressure and death. Treatments include rest and intravenous fluid in severe cases. There are no anti-viral medications or vaccines.

Making a dengue vaccine has been particularly difficult because of the virus’s unique properties. Normally, a viral infection leads to the development of antibodies that help control and eliminate the virus. In the case of dengue, sometimes people develop antibodies that actually help the virus grow better in people. This is called “antibody dependent enhancement,” and it is known to cause more severe symptoms, especially among people experiencing repeat dengue infections. Because of this phenomenon, it has been particularly difficult to make a dengue vaccine. It’s a perfect topic for a doctoral student interested in a career in vaccine development.

Dissertation on dengue:

Corbett is using samples from a cohort of Sri Lankan children who were infected with dengue to determine how antibodies play a role in clinical outcomes.

Her preliminary findings: some kids who are exposed to dengue have antibodies that are specifically tailored to just one strain of dengue virus, whereas other kids have broader responses that target several strains. Corbett has discovered that children with narrowly focused responses are more likely to get sick when exposed to another dengue infection than are kids with broadly focused responses. Corbett thinks that the broader response plays a role in protecting people from developing symptoms. She’s writing up her findings now.

Sri LankaSojourn to Sri Lanka:

Thanks to her Off-Campus Dissertation Fellowship, Corbett will expand her analysis to further explore the pathogenesis of the dengue virus.

There are four types of dengue — labeled 1 through 4. According to epidemiological studies, Dengue 1 had not been a virulent type in Sri Lanka. But in 2009, a wave of Dengue 1 pushed through Sri Lanka, causing unusually severe symptoms.

During her fellowship, Corbett will revisit the site where her cohort samples were collected so she can obtain more up-to-date samples that could help her determine if there is an antibody response that correlates with the more severe Dengue 1 outbreak.

“Not understanding these issues is one reason why vaccine trials have failed in the past,” Corbett says. “We need to know what happens naturally in people when a virus infects someone.”

The Future:

Corbett hopes to defend her dissertation after the summer of 2014. She already has interviews lined up this winter at the National Institutes of Health. “I don’t think I’ll keep working on dengue,” Corbett says. “But I do want to continue working on similar viruses with these types of overarching vaccine questions.”

And what if she finds some answers? “There will always be more questions. That’s what science is; question after question. There will always be another one to answer.”