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A UConn researcher working to develop a vaccine against the Zika virus discusses what’s known about this emerging infectious disease.
UConn pathobiologist Paulo Verardi and his Ph.D. student are working to develop a vaccine against this emerging infectious disease. (Map source: CDC)
Within the past few weeks, travel warnings and a startling rise in a rare birth defect have brought a virus few people had heard of into the headlines. Zika virus is of growing importance, and UConn pathobiologist Paulo Verardi has wasted no time in learning more about the virus and beginning to design a vaccine for this emerging infectious disease.
An expert in virology whose research interests involve the development of vaccines and means of improving vaccine safety and efficacy. His work also involves emerging infectious diseases such as Zika virus, for which he hopes to quickly generate a safe and efficacious vaccine using new vaccine technologies developed by his research group.
A member of the Center of Excellence for Vaccine Research (CEVR) in the College of Agriculture, Health, and Natural Resources at UConn. He has worked on vaccinia virus immunomodulating genes, cytokines as attenuating and immunoenhancing agents, the development of a vaccinia virus-based vaccine for rinderpest, safer and more efficacious vaccine vectors for smallpox and AIDS, vaccines and diagnostics for Rift Valley fever, and foot-and-mouth disease.
Ph.D. Comparative Pathology, University of California, Davis
B.S. Biological Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
There’s a lot of media attention on the Zika virus at the moment. Can you provide a quick overview of what is known about the virus right now?
Zika virus is a relatively new pathogen and therefore causes what we call an emerging infectious
disease, with dengue fever-like symptoms. In fact, Zika virus is related to the dengue virus and is transmitted by the same mosquitos in the Aedes genus. Currently there are three viruses in the Americas transmitted by Aedes mosquitos that cause disease with similar symptoms: dengue and Zika virus, as well as the unrelated chikungunya virus.
The Zika virus was discovered back in 1947 in Uganda, but until the mid-2000s, only a handful of human cases were documented. But in 2007, a large outbreak occurred in Micronesia, followed by a 2013 outbreak in French Polynesia. Unlike dengue and chikungunya, Zika virus typically causes a mild disease (mild fever, skin rash, conjunctivitis), with perhaps as much as 80 percent of those infected not developing any clear symptoms. Zika virus infection can also favor the development of Guillain-Barré syndrome, a neurological complication from infection that is luckily rare.
Early last year, an outbreak started in South America, particularly in the Northeastern part of Brazil. Since the disease is mild and any symptoms resemble dengue or chikungunya virus infection, the outbreak was initially not detected; and when it was, it looked relatively benign. It was not until sometime last October that cases of microcephaly, a rare condition in which the fetal brain does not develop properly, started rising in that region. I’m originally from Brazil and I read the Brazilian news in Portuguese every day during my lunch break. Back in October, I was particularly puzzled by the news that this one particular hospital reported two babies being born with microcephaly on the same day. Microcephaly is rare, so at that point Brazilian health officials quickly considered a link between the Zika infection and microcephaly, and in November they found the virus in the amniotic fluid of two pregnant women whose fetuses had microcephaly. The link has been further supported this past week by a Brazilian research team that showed that the virus seems to cross the placental barrier that normally protects the fetus from other infections.
Should people be worried?
Once Brazilian officials learned about the link between Zika virus and microcephaly, they took the unprecedented action of advising women in the most affected areas to avoid or delay pregnancy. The Brazilian outbreak has now spread to a number of countries in South and Central America, including the Caribbean, and more recently, Mexico, and thus cases of microcephaly in these areas are also likely to start rising in the next few months. Even in Brazil, as infected pregnant mothers continue to reach full term, these numbers are expected to increase. That has led the Centers for Disease Control (CDC) to recently issue travel advisories to the countries battling the outbreak. So at this very moment, unless you have traveled or are planning to travel to these areas while pregnant, you should not be worried.
Do you see Zika becoming widespread in the U.S.? If so, how soon?
In the U.S., a dozen cases of human infection have been reported, but so far they have all been acquired abroad. The potential for what we call autochthonous, or local, transmission exists, because the Aedes mosquitos that are required to transmit the virus are present in the U.S., particularly in the southeast. Locally acquired cases of Zika virus infection have been reported in Mexico and Puerto Rico, so the potential for active transmission in the U.S., particularly as summer approaches, is real. The World Health Organization (WHO) now estimates that all countries in the Americas, with the exception of continental Chile and Canada, where Aedes mosquitos are not found, will likely have outbreaks. As an example, Hawaii is currently battling an outbreak of dengue fever in the Big Island transmitted by Aedes mosquitos. But in general, any outbreaks in the U.S. will be restricted to areas where Aedes mosquitos are found, and careful surveillance, vector control, and other preventive practices such as use of insect repellent, should minimize their effects.
Can you tell us about the vaccine technologies your group is working on?
Since past outbreaks were uncommon and the disease typically mild, no vaccine or therapies for the disease have yet been developed. Back in November, as I read the Brazilian news about the outbreak and its link to microcephaly, I immediately started working on the development of a vaccine. I specifically work on vaccine platforms and, together with my students at UConn, had just finished the development of a new method to quickly develop vaccines. I then asked Brittany Jasperse, a pathobiology Ph.D. student in my laboratory, to use our method to design a number of vaccines for Zika. Brittany is now working diligently to advance this process, and we expect to test the immunogenicity of these new vaccines very shortly.
How far off is a vaccine?
The pathway to a licensed vaccine is a long one. First, vaccines must be developed and tested in pre-clinical trials with small animals. That is what our group is doing now. If the vaccine is shown to be safe and efficacious, it then proceeds to further pre-clinical trials in large animals, and progresses into human clinical trials. The whole process takes years, just consider the fact that we still don’t have a licensed Ebola virus vaccine, although we are close to it. The National Institutes of Health (NIH) just indicated this past week that it considers Zika virus a high priority pathogen for research funding, so that will certainly help and speed up the process of developing vaccines and better clinical diagnostic tests.
Is the damage done to a developing fetus only seen in active infections, or is there a risk of a latent infection causing damage years after initial infection?
We really know very little about Zika virus biology and infection. In fact, the link between microcephaly and Zika has only been found in this current American outbreak, suggesting that perhaps the virus has only recently acquired this property, possibly due to mutations. Looking back, we now realize that the Brazilian outbreak started in early 2015, but the microcephaly cases were only first diagnosed as babies started being born nine months later in October. So at this point, it is too early to know the effects that infection in pregnant women or mothers-to-be will have. We are still trying to learn the effect of infection in later stages of pregnancy or in babies that don’t show microcephaly but may still be affected. So, the short answer is that it’s too early to know. It’s also important to note that the virus can be found in the semen of infected men, so the potential for sexual transmission also exists, although it seems to be rare.
Is there anything else about Zika you feel people should be aware of?
This is truly a very special emerging disease. Unlike Ebola virus infection, that causes severe symptoms and in most cases death, infection with Zika virus is typically asymptomatic, but sadly extremely consequential for pregnant women and their babies. It’s really an unprecedented, fluid situation, with much more to learn. The city of Rio de Janeiro will be hosting the summer Olympic Games in a few months, and local transmission of Zika has been reported in the host city. However, Brazilian authorities are working hard to minimize its impact during the Games, so if you are planning to attend the Olympics this summer, I would not cancel the plans unless you are pregnant or planning to get pregnant during that period. If you are planning to travel to one of the affected countries or if you live in an area with Aedes mosquitos in the U.S., the CDC and WHO websites are good resources to learn about how to protect yourself from mosquito bites, such as use of repellent, long sleeves, mosquito nets, etc.
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