Vaccines can be one of the most powerful and effective public health interventions, as experiences with smallpox and polio make clear. But vaccine development itself is quite difficult, which is why there are (relatively) few vaccines out there. Look at dengue, for example: it’s a longstanding viral problem in tropical areas, and would seem to be just the sort of thing that could be beaten down by a vaccination program. But there are four major serotypes, and immunity to one doesn’t translate to immunity to the others, which means that you’re going to have be be vaccinated all four ways. To make things worse, the second round of infection is often much worse than the first (if you get the third and fourth varieties later on, they’re usually milder by that point, anyway). Sanofi-Pasteur has been working in the area for years in full knowledge of these and other problems) and was able to launch a vaccine (Dengvaxia) in 2016.
But last fall, the company issued a warning update, since clinical evidence had accumulated showing that the second-worse-infection problem could actually be caused after treatment with the vaccine as well. The company recommended that the vaccine only be administered to people who had previously been infected, where it would indeed prevent subsequent round of dengue. The problem is, there’s no widely available test to check if you’ve been infected that first time or not – and if you haven’t, it seems that you really shouldn’t get Dengvaxia. As far as I know, this standoff remains unresolved.
Consider next the case of the Zika virus. In 2016 there was a flat-out epidemic of Zika infection in South and Central America, an especially serious problem given its apparent effects on the developing fetus. A number of companies started work on a Zika vaccine, because this looked like joining the (already too lengthy) list of endemic mosquito-borne diseases that come back around every year.
Something unexpected has happened, though: Zika cases in South America have done nothing but fall steeply from their 2016 peak. That was going to happen to some extent anyway as the southern hemisphere changed seasons, but although the virus did come back in 2017, it was at far lower levels. 2018 has been even lower. For example, in 2016, Puerto Rico, the US Virgin Islands, and American Samoa had 36,000 cases of Zika, but in 2017 there were 665, and the last numbers I saw for 2018 were about tenfold lower than that. Where did it go? It’s hard to answer a question like that one, but you have to wonder if the virus started causing some sort of competitive disadvantage in its mosquito vector (to pick one explanation).
That leaves the people developing a Zika vaccine in an unexpected situation: how do you test for efficacy in preventing a disease that no one is coming down with any more? And in populations where a large number of people already have immunity thanks to the 2015-2016 epidemic? Now, there’s definitely a chance that the virus could come back again – that sort of thing certainly happens. But there’s also no guarantee that the next round of it, if there is a next round, will have the same profile versus the vaccine. Whatever factor made the virus disappear as a human threat will have to change again for it to re-emerge, and we really don’t know what that would involve.
So that’s led to a proposal to deliberately infect people with Zika in order to have enough patients to test the vaccine in. That sounds a bit crazy at first, like contracting for some occasional random arson to keep the fire department in practice, but the “human challenge model” is a longstanding route of vaccine development (here are some reviews on its use in cholera, respiratory viruses, dengue, and in other areas). It’s not without its ethical challenges, though, of course, which have come up again with the Zika proposal. What are the long-term effects of Zika infection? What are the chances that trial subjects could spread the disease to others? What sort of safeguards are in place to prevent women in the study from becoming pregnant? A 2017 trial proposal at the NIH was put on hold after an ethics panel recommendation, but another one is in the works now.
If you’re going to prove that a Zika vaccine works, a human challenge may be the only way. Doing that with rhinovirus is considered completely acceptable, while doing that with (say) Ebola is completely not. Where on that spectrum does Zika fit? (Interestingly, some current dengue vaccine work is including Zika vaccination as a component, which makes one wonder how that part will eventually be tested as well). If Zika itself really has vanished, this will all be a moot point – but how can anyone be sure that it has?