Is There a Zika Vaccine Within Sight?

Investigational Zika Vaccine Enters Phase 2 Testing

Zika virus research
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Zika virus is spread by a genus of mosquito called Aedes which lives in tropical and subtropical environments. Zika can also be spread among those infected through sexual intercourse. Most people infected with the Zika virus experience no symptoms. Others experience fever, rash, red eyes, joint pain, headache, and muscle aches. These symptoms can last about a week. However, if a pregnant woman is infected with Zika, the risk of severe birth defects in the baby—such as microcephaly or small head—skyrockets, which is why Zika can be so scary.

Infection with the Zika virus is rampant in the Caribbean, Central America, and South America. Although Zika can be prevented with insect repellant, mosquito netting, and clearing your living area of stagnant water in which Aedes mosquitoes breed, there is no cure for this illness. Scientists are in a race to discover a vaccine that can effectively prevent Zika in countless pregnant women as well as others across the globe.

After beginning early-stage (Phase 1) human testing on experimental Zika vaccines in 2016, in March 2017, the Vaccine Research Center (VRC), which is part of The National Institutes of Health (NIH), announced plans to advance a candidate vaccine into Phase 2 (Phase II) clinical trials. In Phase 2 clinical trials, more people will be tested, and if results look promising, we’ll be one step closer to an effective Zika vaccine, which denizens of the global south so desperately need.

Zika Vaccine Explained

The Zika virus vaccine currently being developed is using a platform similar to that used to previously develop a West Nile vaccine. By using a similar strategy, researchers can ostensibly facilitate the whole process of developing an effective vaccine. Of note, the Zika virus and West Nile virus are similar and are both type of flaviviridae, a family of viruses.

The Zika vaccine is a DNA vaccine, which contains a small circular bit of DNA called a plasmid. Into this plasmid, researchers have inserted genes that encode two proteins found on the surface of the Zika virus. Once injected into muscle, these proteins assemble into particles that mimic the Zika virus. These non-infectious particles trigger an immune response which should help the body ward off future infection with the Zika virus.

A DNA vaccine can have a lot of advantages including the following:

  • DNA vaccines can create different types of immune responses.
  • They are more stable for storage. DNA viruses aren't affected by changes in temperature, which matters because Zika spreads in tropical and subtropical environments that are hot. Furthermore, DNA vaccines don’t need to be refrigerated. Because this type of vaccine remains stable in a wide range of temperatures, they are easier to use, easier to administer, and cost less.
  • The vaccine doesn't involve any sort of infectious pathogen. The whole virus isn't used; instead, pieces of DNA are used. There isn't a weakened virus that's alive (a live attenuated virus), and there isn't a killed virus. So although other vaccines have been quite safe with killed virus or live attenuated virus, no one has to worry about there ever having been an infectious virus in a DNA vaccine.
  • This type of vaccine is easier to manufacture on a large scale. Easier production will help with future epidemics of other pathogens as well. If we can quickly respond with a DNA vaccine to Zika, we will know how to more quickly scale up a response to other new viruses which may emerge.
  • Based on previous research with other DNA vaccines, with the Zika DNA vaccine, it may be possible to distinguish immune response in those who have been vaccinated from those who have been infected. This distinction helps track how the virus is being spread and whether the vaccine is successful.

Phases of Clinical Trials Explained

In the United States, drugs, vaccines, and so forth are subjected to steps of clinical testing called phases.

Each of these phases answers different questions.

According to the NIH

Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

VRC 705

VRC 705 refers to the entire clinical trial testing the NIH's new Zika vaccine. The Phase 2 portion of this trial consists of two parts: Part A and Part B.

Phase 2A will extend on Phase 1 clinical trials and further evaluate the safety of the vaccine as well as its ability to stimulate immune response in people living in areas where the Zika virus is locally transmitted. It will also determine optimal sites of infection and optimal doses of the vaccine.

Phase 2A will involve 90 healthy men and healthy non-pregnant women between 18 and 35 from three separate locations: San Juan, Houston, and Miami. (In the United States, Zika has been locally transmitted by mosquitoes in Miami and, to a lesser degree, southern Texas.) All participants will receive the investigational vaccine, with one group receiving a standard dose and the other group receiving a higher dose. The vaccine will be administered three times during three separate visits, each four weeks apart, and participants will be followed for 32 weeks total.

Phase 2B will be bigger and involve 2400 healthy men and healthy non-pregnant women. In addition to Houston, Miami, and San Juan, the virus will also be tested among participants from Costa Rica, Mexico, Panama, Peru, and Brazil. More sites could be added in the future.

Participants in the Phase 2B arm will receive either the active investigational vaccine or a placebo (sham vaccination). The vaccine or placebo will be administered on three occasions, each four weeks apart. This experiment is randomized and double-blind meaning that participants will be randomly assigned to receive either the active vaccination or placebo and neither investigators nor participants will know which is being injected.

Phase 2B participants will be followed for about two years. Researchers will document how many people are infected with Zika virus as well as any adverse effects. Presumably if the vaccine works, far fewer people receiving the investigational vaccine should become infected with the Zika virus than those receiving the placebo. Vaccination safety will also be monitored. Of note, both participants receiving active vaccine and those receiving placebo will be counseled about Zika prevention (insect repellents, mosquito netting, and so forth).

Pregnant women will not be eligible to participate in the trial. Women participating in the trial will need to use birth control. If a woman does become pregnant during the trial, she will no longer receive the product but will be followed up for some further testing.

In Phase 2, the vaccine will be administered into either the arm or thigh muscles. During Phase 2A, researchers will determine which site is best.

Initial results from Phase 2A/2B will be available in 2017. The trial will conclude in 2019. Timing of the trial could be affected by the worldwide intensity of Zika transmission and effectiveness of the investigational vaccine.

Other Zika Vaccines in Development

There is work on multiple DNA vaccines. These vaccines can use different stretches of DNA or RNA. Some may target specific proteins.

These multiple vaccines will then be tested to see if they create antibodies and immune responses which we expect to protect us from Zika.

Here are some different types of investigational vaccines in the works:

  • A purified inactivated Zika virus called ZPIV (Zika Particle Inactivated Vaccine) is in Phase 1 testing at the Walter Reid Army Institute of Research. This vaccine is being developed in a fashion similar to those developed for Japanese encephalitis and dengue. Like Zika and West Nile, Japanese encephalitis and dengue are both flaviviridae. The NIH is helping with development of this vaccine.
  • A live-attenuated Zika vaccine investigational vaccine, which protects against Zika and dengue, has been developed by the NIH. This candidate has yet to be tested in people. Although live-attenuated viruses are, in fact, live and not killed, they have been weakened so as not to cause infection.
  • Several mRNA vaccines are in the works. According to Schlake and co-authors, “mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines.”
  • A Zika vaccine that employs a genetically engineered version of the vesicular stomatitis virus (VSV) is in development. VSV typically affects cattle and has also been used to create an investigational Ebola vaccine. This vaccine is in a very early stage of development and still needs to be tested in tissue and on animal models.

Unknowns Can Influence Vaccine Production

There's still a lot we need to learn about Zika: Does dengue make Zika worse? Does our immune response, like with dengue, make Zika worse? Are some people more vulnerable to Zika? How long does Zika last in pregnant women? How long does it last in sperm?

Answers to these questions and more could determine how vaccines help us fight Zika and affect the production of the vaccine. While there is still a lot to learn, experts are making progress—as evidenced with the initiation of Phase 2 trials by the NIH—and hope for a functioning vaccine is high. In the meantime, it’s imperative that people—especially women who are pregnant or planning on becoming pregnant—do their best to avoid infection with the virus by using insect repellent and taking all necessary precautions.

Sources:

FAQ ClinicalTrials.gov – Clinical Trial Phases. www.nlm.nih.gov.

NIH. Phase 2 Zika vaccine trial begins in U.S., Central and South America. News Release. 2017.

Schlake, T, et al. Developing mRNA-Vaccine Technologies. RNA Biology. 2012; 9(11):1319-1330.

NIH. VRC 705: Phase 2/2b Trial Testing the NIAID Zika Virus Investigational DNA Vaccine. Question & Answer.

CDC. Zika Virus Overview.

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