A new study of the live-attenuated tetravalent (four-strain) dengue vaccine TV003 shows that the vaccine was safe and immunogenic in healthy adults who had prior flavivirus exposure.
The National Institutes of Health (NIH)-backed vaccine was tested in a small group of volunteers in Baltimore and Burlington, Vt.
TV003 has already been shown to be safe and immune-producing in phase 2 trials, but data published yesterday in PLoS Neglected Tropical Diseases showed the results of using the vaccine in 58 healthy adults aged 18 to 50 who had prior exposure to a flaviviruses, including dengue, yellow fever, West Nile Virus, or St. Louis or Japanese encephalitis. Evidence of prior infections was determined by neutralizing antibodies in serology testing.
The subjects were given two doses of TV003, spaced 6 months apart, and then evaluated their rates of seroconversion, tetravalent response, and mean neutralizing antibody titer. TV003 vaccination led to 89% seroconversion against all four strains of dengue virus in the study subjects.
"In particular," the authors wrote, "prior flavivirus exposure was associated with a sustained effect on DENV-2 seropositivity following vaccination with TV003….Overall, 87% of flavivirus-experienced subjects achieved a tetravalent antibody response and an additional 10% achieved a trivalent response to vaccination following a single dose of TV003."
No evidence of ADE
The study addresses one of the feared outcomes of dengue vaccinations: antibody-dependent enhancement (ADE).
Last year, Sanofi-Pasteur's Dengvaxia vaccine was rolled out in five countries amid controversy that the vaccine caused ADE in recipients who had not been previously infected with the mosquito-borne virus. Dengue virus has four strains, and previous infection with one strain can make subsequent infections with other strains worse.
In post-licensure trials, Dengvaxia was tied to higher rates of hospitalization due to dengue in children. The vaccine was acting as the recipients' "first exposure" to the virus and producing ADE.
At the time, leading dengue researcher Scott Halstead, MD, who was not involved in the study, told CIDRAP News, "Vaccine recipients less than 5 years old had five to seven times more rates of hospitalizations for severe dengue virus than placebo controls."
Dengvaxia is not recommended for use in patients under the age of 9, which Halstead said was a proxy for being "dengue naive."
Results from both Denvaxia and TV003 have implications for Zika virus, another flavivirus that's shown cross-reactivity with dengue, chikungunya, and yellow fever.
Last March, researchers studying TV003, which is currently in phase 3 trials in Brazil, said it could be used as a framework for a Zika vaccine.
See also:
May 8 PLoS Negl Trop Dis study
Mar 17, 2016, CIDRAP News story "Dengue vaccine performs perfectly in small trial"
Jul 28, 2016, CIDRAP News story "Contrary dengue vaccine response hints at possible problems with Zika"
