The World Health Organization (WHO) declared that the Zika virus constitutes a Public Health Emergency of International Concern on Feb 1. Since then, public health institutions and biomedical researchers worldwide have been working on potential ways of preventing this newly emerging crisis.
Many have turned to vaccines as a viable option, and focused resources on developing a successful therapeutic candidate.
News on the initiation of a Phase 1 clinical trial for a vaccine that showed positive results in animal studies, as well as the partnership between the U.S. Department of Defense and Sanofi Pasteur to expedite development of their killed virus candidate, has given the public hope that such a vaccine might soon exist.
To help us understand the complex process of getting a vaccine ready for an emerging viral epidemic, such as Zika — and why it might take longer than expected — Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and president of the Sabin Vaccine Institute, spoke with BioNews Texas. He offered insight as to what we can realistically expect regarding a timeline for the availability of a vaccine.
Can you explain to our readers the importance, if any, of a vaccine candidate getting approval to move forward to a Phase 1 trial?
After a vaccine is produced, and it has to be produced in a certain way under what is called “good manufacturing practices” — also sometimes called “current good manufacturing practices” (CGMP) — you then, if the company is in the U.S., submit a document called an “investigational new drug” (IND) application to the U.S. Food and Drug Administration (FDA). They review it to ensure there is evidence the vaccine may be effective, such as testing in laboratory animals but also quite a bit of safety studies — including what is called a toxicology study that is done by a certified contractor, [who] knows how to conduct toxicology studies — and then you can receive permission to begin the Phase 1 trial if there are no objections.
A Phase 1 trial is then carried out for safety. And oftentimes with that safety study they [the FDA] will look for evidence that it induces an immune response. The Phase 1 study is often done in healthy adult volunteers and, if successful, followed by expanded safety studies in immunogenicity Phase 2 trials.
Phase 2 trials are larger, and at that point you are getting some indication of whether or not the vaccine is effective, because you are oftentimes conducting that in a field-like setting. If those [trials] are successful, you then move on to a Phase 3 study, sometimes known as a pivotal trial, that is the definitive study needed for the FDA to approve your vaccine for licensure. The Phase 3 trials are larger studies, and they are more involved and they could also be quite expensive.
When it comes to the Zika vaccine, there are several candidates out there now that are advancing towards pilot-scale CGMP manufacture, and then moving into Phase 1 clinical trials to show that the vaccine is primarily safe.
With the Zika vaccine we are going to have a problem, in that while several vaccine candidates will move into Phase 1 trials, I am concerned that the trials will then stop, or at least slow down quite a bit.
There are a couple of reasons why I am concerned about that:
1) We know that the Zika virus has the ability to cause what is known as Guillain-Barré syndrome, which, generally speaking, is an autoimmune response against the virus, and that autoimmune response cross-reacts to the myelin on your peripheral nerves, possibly causing nerve damage that is sometimes severe enough to lead to paralysis.
Based on that finding, I think it is likely that after Phase 1 trials the FDA will want to see extended safety studies, to ensure that the vaccine also does not cause Guillain-Barré syndrome — because in some cases the vaccines will have a similar antigenic structure to the actual virus.
2) The other worry is who this vaccine is intended for — pregnant women — and from the regulatory perspective that is about the highest bar there is, and understandably so, because you don’t want to give any drug or vaccine that could potentially cause any harm to the mother or fetus. So that is also going to take extensive safety studies.
What all this means, practically speaking, is that for the vaccine, we will move pretty quickly into Phase 1 trials for several candidates. But then I think things will really slow down after that, and we will not have the vaccine in time for this epidemic.
Realistically, when do you think we will have a viable candidate?
I think we are at least a couple of years away.
You have commented previously that you are hesitant to get hopeful about a DNA vaccine going to Phase 1 trials. Can you explain why?
There are several different vaccine platforms being developed; there’s DNA vaccines, attenuated vaccines, chimeric vaccines, and recombinant protein vaccines. Each of these vaccine platforms has advantages and disadvantages. There is no one “aha” this is going to be it.
In the case of the DNA vaccines that are being developed — including one by a company out of Pennsylvania called Inovio, they sent out a press release about it. I don’t know the particular details about that vaccine, but what I do know is that DNA vaccines show a lot of promise in mice, but that protective immunity is often not reproduced in people. So what we have seen now in the biomedical literature is dozens, if not hundreds, of DNA vaccine candidates that worked in mice, but none of them have progressed to a licensed human vaccine. None. We have no licensed DNA vaccines for people.
The reason is, at least in my experience, that when you take similar vaccine candidates that are working in mice and showing protection, it doesn’t translate to humans — it doesn’t give you the same level of immune response.
In the case of Zika, what you are going to want to see are high levels of neutralizing antibody, and to my knowledge, we have just not seen that in DNA vaccines. In biomedical science, you never say never, but so far the advancement of DNA vaccines is disappointing.
This is especially disappointing because DNA vaccines are relatively easy to make, and they are also heat stable. Because they are nucleic acid and not protein, they withstand environmental extremes better than protein. So if you got a DNA vaccine that worked, it would be great for resource-poor settings, and tropical environments it would solve a lot of problems. But so far, it has not panned out.
Perhaps this vaccine will be the first, but I think we must be realistic about what will probably happen.
About Dr. Peter Hotez
Dr. Peter J. Hotez is dean of the National School of Tropical Medicine and professor of Pediatrics and Molecular Virology & Microbiology at Baylor College of Medicine, where he is also chief of a new section of Pediatric Tropical Medicine and the Texas Children’s Hospital endowed chair of Tropical Pediatrics. He is the president of the Sabin Vaccine Institute.
Internationally recognized, Dr. Hotez leads the only product development partnership for new vaccines for hookworm infection, schistosomiasis, and Chagas disease. He co-founded the Global Network for Neglected Tropical Diseases in 2006 to provide access to essential medicines. He is the founding editor-in-chief of the journal PLoS Neglected Tropical Diseases.
In 2015, Dr. Hotez was selected by the State Department to serve as a United States Science Envoy.
BioNews Texas has spoken with Dr. Hotez on other aspects related to the Zika epidemic. To read that interview, please click here.