The first Phase-1 human clinical trial of a vaccine for Zika virus is set to begin in the coming weeks, with the U.S. Food and Drug Administration (FDA) green-lighting it. The DNA vaccine (GLS-5700) developed by the U.S-based Inovio Pharmaceuticals and GeneOne Life Science, South Korea, has already been tested on animals and found to elicit “robust” antibody and T cell responses.
The human trial will be carried out on 40 healthy adults to evaluate safety, tolerability and immunogenicity and the interim results are expected before the end of the year. But it may take a couple of years to know if the vaccine works against Zika. According to the World Health Organisation (WHO), four of the 14 companies working on a candidate vaccine have reached the preclinical stage.
It is a remarkable achievement to be in a position to carry out clinical trials on humans as the time taken to develop the experimental vaccine has been shrunk significantly. Though the current Zika outbreak began in Brazil in May 2015, the impetus and urgency to develop a vaccine came about only after February 1, 2016 when the WHO declared Zika as a global public-health emergency of international concern.
A major lesson learnt from the Ebola epidemic is the overwhelming need to start vaccine trials quickly. Large-scale trials of Ebola vaccine began about a year after the Ebola outbreak was first reported and just as the number of people infected with Ebola was reducing. A precious opportunity to quickly develop a vaccine in an emergency situation was lost for want of sufficient number of infected people to test the vaccine.
As of June 15, the Zika virus has already spread to 60 countries and territories. Even as it spreads geographically, there has been a decline in cases of Zika infection in some countries or in some parts of countries. But it is unlikely that vaccine trials for Zika may suffer from want of infected people. “At this stage, WHO does not see an overall decline in the outbreak,” the June 16 WHO situation report says.
The big challenge
Yet, Zika vaccine development faces a huge hurdle that Ebola vaccine did not. The candidate Zika vaccine has to be tested on pregnant women as some babies born to women infected with the virus during pregnancy suffer from microcephaly. Hence, testing a candidate vaccine on pregnant women or women in the childbearing age can take place only if the vaccine has been found to be very safe in men and non-pregnant women. Also, extensive safety data of vaccinated pregnant women and those about to become pregnant will be required before the vaccine gets approved for commercial use.
While the candidate vaccine that will be tested by Inovio and GeneOne be a DNA vaccine, like the one that the U.S. National Institutes of Health (NIH) is also developing, a March 9 report of the WHO clearly states that developing vaccines that use inactivated (dead) viruses for use in women of childbearing age or pregnant women will be a research “priority”.
Inactivated virus used in vaccines cannot multiply and hence considered safe for use in pregnant women. After all, babies born to mothers infected with Zika are at a risk of having a small head (microcephaly).
As of June 15, 1,581 cases of confirmed microcephaly and other nervous system disorders cases have been reported in Brazil; microcephaly is yet to be ascertained in another 3,000-odd babies.
It is to address this critical issue of babies born with microcephaly that the WHO in its March 9, 2016 report clearly stated that “vaccination of pregnant women and women of childbearing age is the main target”. To achieve this goal, the world health body intends to have in place “pragmatic strategies to fast-track the development of a safe and effective product”.
Work is under way for the development of an emergency vaccine target product profile, says the WHO. The target product profile will serve as a guide to consult and build consensus on regulatory requirements for Zika vaccine evaluation and registration.
Testing therapeutic drugs is a not a priority as a majority of infected people are either asymptomatic or have mild disease effects. Also, testing therapeutic drugs in pregnant women is complex and challenging. Safety will be a key issue as long-term use would be needed by pregnant women. It for these reasons that the WHO has prioritised preventive vaccine and vector control as control tools.