Dengue fever vaccine proves 100% effective in human trials
wired.co.uk
wired.co.uk
The whole challenge in creating a dengue vaccine is that it has to protect against all four serotypes (called a tetravalent vaccine). Incomplete protection against one of the serotypes could potentially lead to an even worse infection if you are infected, through a process called antibody dependent enhancement: https://en.wikipedia.org/wiki/Antibody-dependent_enhancement This is why vaccine development against dengue has been so painstakingly slow.
The candidates in this trial were only challenged with one serotype, DENV-2. Therefore, we have no way to know if the tetravalence of the vaccine actually achieved efficacy against all four serotypes (although promisingly, antibodies against all serotypes were seen in 92% of the patients). The sample size is also quite small (N = ~20). This is why the original article states its impact conservatively as "This model may serve as an early check for dengue vaccine candidates, limiting the risk of conducting large unsuccessful trials" and furthermore "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas." Here's how you write a more honest headline and summary for lay people: http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv...
I don't intend to detract from the achievement here, but I don't like when headlines oversimplify the implications of a clinical trial. It sets unrealistic expectations and decreases the public's trust in proper vaccine research.
Disclaimer: I am doing research with a lab that studies dengue virus, and we have collaborators that are working on a commercial vaccine.
Are you sure about "millions of deaths" ? Dengue fever fatality rate is lower than 1%. I'm not saying this is not a grave disease, but it's hardly something that kills as much as many other viruses out there.
You're obviously much more familiar with this subject, but doesn't the quote from the original article refer to the testing model itself (i.e. "dengue human challenge model"), rather than the efficacy of the actual vaccine?
> this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article.
To be fair, it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article ("The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model" vs "Dengue fever vaccine proves 100% effective in human trials").
> I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths per year
I tried finding estimates of infections and deaths per year, but didn't find any that are close to millions/year. Do you have a source for that? The closest I got was from the CDC/WHO: The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, including 500,000 DHF cases and 22,000 deaths, mostly among children. [0]
Yes, it does, precisely because the trial is about a human challenge model that uses an attenuated virus. It may or may not be representative of efficacy against natural infections by wildtype viruses, hence the second statement by the authors that "the true efficacy of TV003 can only be established by performing a phase 3 trial in endemic areas."
> it doesn't seem like Wired has editorialized/misrepresented at least the headline much relative to the original article
I believe the inclusion of "in a human challenge model" in the original title is quite significant to its interpretation, but it's precisely the kind of detail that would get overlooked by people unfamiliar with vaccine trials. A researcher in the field would know that human challenge models may or may not be representative of protection against natural infections, but the Wired title ignores that distinction and instead sows confusion by saying the vaccine simply "proves 100% effective".
> millions/year
You're right, I meant hospitalizations; sorry about that. Dengue hemorrhagic fever is a life-threatening condition that warrants hospitalization, and dengue fever in more vulnerable patients also can result in hospitalization.
The interview with the researcher addressed pretty much all the points you are making and stated that the goal of the trial type was to demonstrate the efficacy against DENV-2 so that they would be able to move forward in a full trial of all four types.
From the article:
"Whitehead and the other researchers said that in the case of dengue, the testing was warranted because they knew that the vaccine appeared to be effective at preventing dengue 1, 3 and 4 viruses through previous testing but needed to learn more about its impact on dengue 2 before proceeding to larger trials that could take three to 10 years and cost tens of millions of dollars."
[EDIT: As pak notes elsewhere, this trial apparently didn't test against all four varieties although there was some evidence it might protect against multiple.]
Having lived in tropical areas where this is prevalent, and having suffered from dengue, this is incredible news. The people who are most affected by this are those who don't have resources to repel these tiny, common insects. They also don't have resources to properly treat this incredibly agonizing, and sometimes fatal, disease.
Lasers, sprays, genetics, and everything else under the sun has been proposed to control mosquitos. Something that controls the thing they spread, which causes so much suffering, is much more exciting.
Not "100% efficient" but nothing really is, nor is that really needed, it's not a boolean thing but a continuum and having any kind of antibody response is better than none; it reduces the chances of more severe disease at least, if not prevent disease all-together.
The point of using an attenuated virus is that this is a "challenge model" that is supposed to simulate an exposure to the real virus closely enough that one can judge if the vaccine is likely working, without exposing the patients to the risks of infection by the full-strength virus. CNN did a much better job than Wired in explaining this. http://www.cnn.com/2016/03/16/health/dengue-vaccine-effectiv...
Therefore, the fact that the placebo group had certain levels of various symptoms (according to the article, 80% had a rash, 20% had nausea, etc.) is still important data for other scientists who are trying to judge if they should use the rDEN2Δ30 challenge model in their candidate vaccine trials. It's not intended to provide data on what natural dengue fever is like, which I agree would be unethical and unnecessary.
In a cancer trial you'd typically compare standard of care with the new drug.
Plus, there are some cancers out there with very few working treatments (so no real SoC) - If SoC is not available you would not consider a placebo group anyway.
What I haven't seen is a clinical trial without a control arm.
In terms of the ethical considers it's not unusual to run a trial for a yeat and then switch every patient over to the new drug.
Second, I know you probably know this, but the purpose of the placebo/control group is to understand if the vaccine is actually doing anything, or whether there is another common factor (possibly placebo effect, but possibly environmental, diet, poorly activated dengue virus, etc...) that is preventing Dengue from taking hold.
I.E. if you have two groups one with the Vaccine, and one with just the Placebo, and both are injected with the dengue virus, and the group with the Vaccine and the group with the placebo both don't contract Dengue - then you have to consider the strong possibility that the vaccine didn't help, but some other factor prevented the two groups from getting dengue.
And, it's far, far better that you try this with 10 people, with a relatively weaker version of Dengue, in a controlled hospital environment where the person can be taken care of, in an area where they are very likely to get the more dangerous dengue regardless of the study, than to come to the incorrect conclusion that you have a workable Vaccine, that you then spend many more hundreds of thousands (millions?) of dollars in broader clinical trials - only to discover the vaccine wasn't really doing anything in the first place.
Is this normal or does it indicate a problem with the peer review at this journal?