Michael Mechanic reports his finding with Dr. Anthony Fauci, the scientist leading the vaccine effort.
“Mother Jones: I’ve read that a DNA vaccine for Zika could be ready for testing as early as September.
Anthony Fauci: Correct. But people get confused about this. It a phase I trial, just the first in a multiphase process of developing a vaccine. We took a DNA construct that we used to develop a West Nile vaccine a few years ago and we just substituted the Zika insert for the West Nile insert, so now it’s a Zika vaccine. We’re producing it in a pilot plant and doing all the preclinical studies you have to do before you go into a human, and we’re pretty certain we’ll get started with the trial in September. It usually takes three to four months and would typically involve around 80 volunteers. So let’s say we figure out that the vaccine is safe and that it induces the kind of immune response we would predict would be protective. If everything looks good, we’ll move into a larger (phase IIb) trial to determine if it’s effective.
MJ: And that would involve rolling it out in Zika-affected areas?
AF: Yes. Otherwise you’d never have enough infections to prove it’s effective. When you finish phase II is dependent on factors that are very difficult to predict. The two major factors are, one, how effective the vaccine is—because the more effective it is, the easier it is to prove it’s effective. The other factor is how many infections are going on in whatever country we’re testing it in: Brazil, Colombia, Puerto Rico, Venezuela—it likely will be multiple sites. If there is a lot of infection, we can probably determine within a year, by the beginning of 2018, if it’s effective enough. And then, depending on the urgency, you can get accelerated approval. Or, the FDA and other regulatory agencies may say you have to test it for another year or so.
‘You can’t be strictly extrapolating to humans, but in the studies we’ve done, the DNA vaccine looked very immunogenic in a mouse.’
MJ: If you need a lot of infections to determine whether a vaccine is effective, then how did you test the vaccine for West Nile, which has resulted in relatively few cases?
AF: We never tested its efficacy. We tested the West Nile vaccine the same way we’re going to do the phase I here. The problem is, we could not get any company to partner with us for advanced development because there was not the perception by any company that this was a vaccine that would be widely used. So we never brought it into phase IIb.
MJ: What are the pros and cons of a DNA vaccine versus, say, using an inactivated virus?
AF: It’s about the same. We have four or five candidates lined up. The first is the DNA. The one behind it is a whole inactivated [virus] particle vaccine. That won’t go into phase I until at least the end of 2016. Then we have a live chimeric inactivated vaccine that won’t go into phase I until the middle of 2017. But there’s no substantial difference. The DNA so far looks pretty good with regard to immunogenicity [strength of the immune response it elicits]. From a historical standpoint, whole attenuated [virus] vaccines tend to be more immunogenic. You’ve got to be careful with mice, you can’t be strictly extrapolating to humans, but in the studies we’ve done, just a few weeks ago, the DNA vaccine looked very immunogenic in a mouse, so it may be as immunogenic as the whole killed [virus].
MJ: How does a DNA vaccine work?
AF: You have a circular plasmid of DNA. You splice into it the gene of the Zika outer coating protein. You inject that plasmid into the muscle of an individual. It goes into the host cells and starts to produce the protein, which your antibodies attack. Interestingly—this is good luck—the vaccine doesn’t just produce soluble outer envelope proteins, it produces them in the form of a virus-like particle. So they look like a small virus, which makes them that much more immunogenic.
MJ: Some researchers worry that Zika is stimulating an autoimmune response in some adults that makes the body attack its own nerve cells, and that’s why we’re seeing these Guillain-Barré symptoms. If that’s what’s happening, is there a danger that a Zika vaccine could actually cause Guillain-Barré?
‘You have to be careful: If you have an inadequate antibody response, you can actually enhance the infection.’
AF: In these small safety studies, if there is a complication like that, it’s probably so rare you wouldn’t pick it up. That’s why, when you do a larger study, you have to do double-blind, placebo-controlled trial. Because whenever you’re developing a vaccine that could have a deleterious effect, you want to make sure you’re not seeing worse effects in the vaccinated than in the unvaccinated. And when dealing with any vaccine, there’s always the danger—and we’ve seen this with flaviviruses [which include Zika and dengue], so you have to be careful—that if you have an inadequate antibody response, you can actually enhance the infection.
MJ: The Senate is preparing to approve a good sized sum for Zika vaccine development. How will that accelerate your efforts?
AF: It won’t accelerate it. It will allow it to happen. You can’t rush clinical trials. If we didn’t get the money, it would either be dramatically slowed down, or it wouldn’t happen.
MJ: At a recent Zika summit, you said ‘I have this ominous feeling we have yet to see the worst of it.’ What were you thinking about when you said that?
“I was saying, ‘My goodness. Every time you wake up, there’s something else that’s bad about Zika.’”
Source: Mother Jones