Nebraska Researcher's New Zika Vaccine Could Have Wide-Ranging Impact

(Photo Courtesy Craig Chandler, University of Nebraska-Lincoln)
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January 8, 2019 - 6:45am

University of Nebraska-Lincoln researchers have discovered a new vaccine for the Zika virus which could have a wide-ranging impact to other vaccines. There have been about 5,700 cases of Zika reported in the United States. About 10 percent of newborns infected with Zika are born with birth defects such as Microcephaly and Congenital Zika Syndrome.  Brandon McDermott of NET News talks with two of those involved with the research on the Zika vaccine.

Brandon McDermott, NET News: Dr. Weaver, you work on vaccines – but how did you get into the Zika virus?

Eric Weaver, UNL Assistant Professor of Biological Sciences at UNL: I had a student in 2016 who was really interested in working on Zika virus and since I work on vaccines we thought why don't we see if we can make a vaccine against the Zika virus? We made 2 different vaccines -- we used those as a backbone to insert some Zika virus structural genes, in order to make this vaccine.

Eric Weaver explains the path Brianna (Bri) Bullard took while at UNL and the contribution she made to the Zika vaccine:

"Bria came in, (she was) very bright, picked up the research very quickly and in one summer – in two months – made two new adenoviral vector recombinant Zika vaccines all in one summer.

She was excited enough about it, that she applied to the graduate program here at Nebraska – in particular to work at the Nebraska Center for Virology. She came back after graduating in December, worked as a technician for about four months and then in 2017 – at the beginning of the summer, as soon as possible – enrolled into the Ph.D. graduate program here at UNL.

In about a year and a half later, we're publishing a paper on an effective Zika vaccine using the vector she made as an undergraduate. So it's a pretty neat success story about Bria as a student."

So, we make both defective so they can’t cause disease and they can express the Zika structural genes in order to induce a protective immune response and so the really interesting fact was that adenovirus type 4 (Ad4) vaccine protected and worked without producing any antibodies and that may be an important finding.

McDermott: Bria, how can antibodies meant to fight seek a virus aggravate Dengue Virus infection in an individual?

Brianna (Bria) Bullard, graduate student in biology at UNL: Sometimes in our bodies against a virus have been shown to actually in the hands dengue a virus infections of certain cell types and so that enhanced infection can actually lead to an increased viremia (viruses present in the bloodstream) – or an increased viral load in an individual, leading to more disease.

McDermott: During research for this Zika vaccine you told me that you almost dropped it, can you tell us what happened there?

Bullard: So when I was first doing my assays (method in virology which tiers concentrations of the virus) to look at the immune response both of these vaccines, I found that the adenovirus 4 didn't actually produce any antibody responses. As Dr. Weaver said, we thought it didn't work. So we almost dropped it right then and moved on. But we decided to go ahead and do a challenge study and see if this was still protective and I'm glad we did because we found it was.

Brianna (Bria) Bullard talks about approaching Eric Weaver with the idea of creating a vaccine for Zika:

"To express my interest in the Zika virus and have Dr. Weaver be willing to let me pursue that was fantastically exciting. So I spent that those two months in the summer working and I came in with minimal lab knowledge, so a lot of that was just fantastic mentoring on Dr. Weaver's part to teach me in the lab how to do all of that.

I also was selected to a postgraduate program within UNL virology. There were only two students chosen out of 500 applicants. It was a two-month program where you spent every day of that time in the lab experiencing what it would be like to go to graduate school. It was exciting and rewarding going through the two months of work.

It’s an amazing experience to make a vaccine. To vaccinate animals and walk into that room and see healthy and unhealthy (animals) – that you have done something that can prevent disease and – it's an amazing feeling."

McDermott: Going from almost dropping it to finding out that this was something special – what was that like?

Bullard: It was really exciting – Dr. Weaver and I sat down and we started talking about it and we thought you know this is actually something really exciting that we should investigate further and so we have written up a grant that we've recently submitted to look for more funding to explore this in further depth.

McDermott: Can this help with studying other vaccines and where do you think this could have the most immediate impact?

Weaver: I think it definitely can help in the design and construction of new vaccines. This little phenomenon that we saw where this adenovirus expresses this structure gene we get great T-cell responses and we don't get any antibody is very intriguing. If we can tease out the mechanism of how this works I would be fascinated to know what this vector is doing to this immune system to down regulate this antibody and still get such strong T-cell responses. To me answering that question is probably the most fascinating aspect of this study. Essentially if you can figure out how to completely turn something off we can probably figure out how to turn something on – in a much stronger way.

McDermott: Would you like to see more studies to determine why there were different results yielded from the two adenoviruses?

Weaver: Yes, I think continuing to study this and figuring out how this is working will be important. Zika virus infections in general – they're bad – they cause disease, but they're not lethal in adults – but they are lethal in unborn fetuses. So that's where we need this vaccine to work the best – so further testing on vaccinated mothers is important and then ultimately to move this into a human political trial. Being a researcher here at UNL, that's where we would have to reach out to colleagues that are at clinical trial networks and units to actually move this further into humans.

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