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An investigational vaccine against all four strains of dengue virus yielded complete protection in a human challenge study, researchers reported -- an approach might help in the development of a vaccine against Zika virus.

In a randomized, blinded, placebo-controlled trial, volunteers getting a single dose of the live attenuated tetravalent dengue vaccine -- dubbed TV003 -- did not develop viremia when they were challenged with dengue 6 months after vaccination, according to , of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

As well, none had two key symptoms -- rash and neutropenia -- often seen in dengue infections, Durbin and colleagues .

In contrast, all the volunteers who were given a placebo injection developed viremia, 80% had a rash, and 20% had transient neutropenia, Durbin and colleagues reported.

The vaccine still needs a full-scale phase III efficacy trial in places where dengue is endemic, and one has just started in Brazil. But the challenge study -- involving an attenuated dengue strain -- is a useful interim step to rule out less promising candidates without the expense and risk of a larger trial, Durbin told reporters in a telephone briefing.

"We think that this is a tool that can really accelerate vaccine development," she said.

But in addition, she said, human challenge studies might help in the development of a vaccine against Zika, which -- like dengue -- is a mosquito-borne flavivirus. "There's an urgent need for a Zika vaccine (and) we think that a human Zika challenge model could be very useful in that endeavor," Durbin said.

Dengue is endemic in the world's tropical and sub-tropical regions with about 400 million infections a year, commented co-author of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

Most of those infections are without symptoms, but the virus can lead to a severe hemorrhagic fever/shock syndrome that can be fatal, he noted.

But dengue virus is a challenging pathogen -- there are four serotypes and any vaccine has to protect against all of them at once because infection with one of the serotypes in the presence of a preexisting immunity to another tends to cause severe disease.

A three-dose vaccine -- -- has been licensed 2016 in Mexico, the Philippines, and Brazil, but its efficacy and safety remain in question. Efficacy against symptomatic dengue has ranged from 30.2% to 60.8% and in two trials, the vaccine did not protect against the second serotype of dengue (DENV-2) despite evidence that most vaccine recipients had developed antibodies to that strain.

Investigators had assumed that production of neutralizing antibodies would correlate with protection against disease, but the experience with CYD appeared to contradict that view, Durbin and colleagues noted.

And importantly, the CYD vaccine also appeared to increase the long-term risk of hospital admission for dengue disease among children younger than nine, the researchers noted.

The TV003 vaccine, Whitehead told reporters, is composed of three full-length dengue genomes (DENV-1, DENV-3, and DENV-4) with a deletion that makes them unable to cause disease, as well as a chimeric DENV-2 strain with the same deletion.

In early studies, the vaccine induced antibodies in 74% of dengue-naïve volunteers, with 92%, 76%, 97%, and 100% seroconverting to DENV-1, DENV-2, DENV-3, and DENV-4, respectively.

Before putting the vaccine into a phase III trial, the researchers noted, "it seemed prudent" to test its efficacy in people who never been exposed to dengue and since the response to DENV-2 was lowest in the early studies, the vaccine's ability to protect against that strain was of greatest interest.

To test the issue, Durbin and colleagues enrolled 48 dengue-naïve volunteers and randomly assigned them to get the vaccine or a placebo, delivered in a single subcutaneous injection. Six months later, the 41 volunteers still in the trial were challenged with an attenuated version of DENV-2 that was known to cause only mild illness.

The results were "very straightforward and quite conclusive," according to co-author , of the University of Vermont College of Medicine in Burlington.

None of the vaccinated volunteers were infected and all of those who got the placebo were, she told reporters.

She added that testing using the other three serotypes in similar challenge studies is planned or under way.

But on the basis of these results, the in Brazil has begun a 17,000-patient phase III trial of the vaccine, with two-thirds of volunteers getting the vaccine and one-third getting a placebo.

Kirkpatrick told MedPage Today that human challenge studies have been used previously -- in malaria, norovirus, and influenza, for instance -- but have to be done carefully. "When you're going to be actually purposely infecting a person, you have to know that it's a completely controllable situation, that it's a mild, controlled infection," she said.

But such studies are valuable when there is an "urgent need" for rapid progress, she said.

A phase III trial, which is ordinarily the first time investigators have evidence of efficacy, can take years, require thousands of volunteers, and cost tens of millions of dollars. A successful human challenge study can give researchers the confidence to go ahead with the pivotal study.

"This really does give you a way to expedite the process," she said.

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