Comment by pak | Hacker News Reader

Comment by pak | Hacker News Reader

While I am of course a huge fan of NIAID and vaccine development against dengue, and I believe that a vaccine that works against dengue will probably be found within our lifetimes and prevent millions of hospitalizations (EDIT: not deaths, sorry) per year, this is a classic example of a downstream news report editorializing the headline and misrepresenting the implications of the original article.

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.

I read a much better (and longer) article on this yesterday in the Washington Post (https://www.washingtonpost.com/news/to-your-health/wp/2016/0...).

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."

> 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"

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]

[0] http://www.cdc.gov/dengue/epidemiology/

> doesn't the quote from the original article refer to the testing model itself

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.

Alright thanks for clarifying!

> vaccine that works against dengue will probably be found within our lifetimes and prevent millions of deaths

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 right, I meant hospitalizations; I goofed.

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