Zika Virus Still Calls for Preparedness and Vaccine Development

Myles Starr

February 21, 2023

Warming US temperatures, the resumption of travel, and new knowledge about Zika's long-term effects on children signal that Zika prevention and vaccine development should be on public health officials', doctors', and communities' radar, even when community infection is not occurring.

Dr Erin Staples

"Although we haven't seen confirmed Zika virus circulation in the continental United States or its territories for several years, it's still something that we are closely monitoring, particularly as we move into the summer months," Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention (CDC) in Fort Collins, Colorado, told Medscape Medical News.

"This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission."

How Zika Might Reemerge

The Aedes aegypti mosquito is the vector by which Zika spreads, and "during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, DC," said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles, California.

Dr Neil Silverman

"On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a US region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that's exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses," said Silverman.

How the Public Can Prepare Themselves

The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way the public can protect themselves.

Staples emphasized, "The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika. It's really important that people are instructed to make a habit of wearing EPA [US Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the US.

"From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population ― the main vector of Zika transmission," said Staples.

Monica Gandhi, MD, MPH, professor of medicine and associate chief of the Division of HIV, Infectious Diseases, and Global Medicine at the University of California, San Francisco, also encourages her patients to wear mosquito repellent but cautioned that "there's no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus."


The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).

Dr Monica Gandhi

"I'm most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection," noted Gandhi.

Moderna's mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the US and Puerto Rico, the results of which were published online January 19 in The Lancet . "The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro," said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.

Dr Brett Leav

"Our mRNA platform technology...can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges," said Leav.

A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is currently underway.

Although it's been demonstrated that Moderna's mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently. the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Silverman.

If approved, provisionally or through a traditional route, the vaccine would "accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the US but also in these endemic areas," said Silverman.

Takeaways From the Last Zika Outbreak

Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the US. A clearer picture of the short- and long-term stakes of the disease has emerged.

According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.

Although a pregnant woman who tests positive for Zika is in a very high-risk situation, "data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options," said Gandhi.

Silverman noted that "new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function." He said, "This is another good reason to keep the potential risks of Zika active in the public's consciousness and in public health planning."

Silverman, Gandhi, and Staples have disclosed no relevant financial relationships. Leav is an employee of Moderna and owns stock in the company.

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