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Multiple doses of NIAID dengue vaccine TV003 may be unnecessary
A single dose of a dengue vaccine developed by researchers at the National Institute of Allergy and Infectious Diseases was capable of preventing infection with a second dose after 12 months, according to phase 1 trial results published in The Journal of Infectious Diseases.
“Data from this study strongly suggest that a second dose of TV003 is unnecessary and provides only minimal benefits,” Anna P. Durbin, MD, associate professor at Johns Hopkins University Bloomberg School of Public Health, and colleagues wrote.
The investigators conducted a placebo-controlled clinical trial of TV003, a live-attenuated tetravalent vaccine, that studied 48 healthy adults in a nondengue endemic area who were enrolled between January and September 2013. The patients were administered two doses of either the vaccine (n = 40) or placebo (n = 8) 12 months apart.
The only statistically significant adverse event observed after the first dose was a vaccine-associated rash in 63% of patients, confirming TV003’s favorable safety profile, according to Durbin and colleagues. Only one patient had a rash after a second dose, indicating that the first dose neutralized vaccine virus replication, they wrote.
After one dose, dengue virus was found in the blood of 43% of patients assigned TV003, including seven patients who had three different serotypes recovered. However, the vaccine virus was not detected in any patients after a second dose.
Phase 2 studies are being conducted in Thailand and Brazil with a single dose of TV003, according to Durbin and colleagues. They said a phase 3 will include a single dose of vaccine and a 5-year follow-up period.
“Because it is not possible to unequivocally equate resistance to re-vaccination with protection against natural infection, future studies will be needed to validate the effectiveness of a single dose,” Durbin and colleagues wrote.
Results for better dengue vaccine ‘promising’
In a related editorial, Alan L. Rothman, MD, head of the laboratory of viral immunity and pathogenesis at the University of Rhode Island, and Francis A. Ennis, MD, professor emeritus at the University of Massachusetts Medical School, said weaknesses in another dengue vaccine — including logistical challenges in the regimen and low efficacy in young children — indicate a need and opportunity for other candidates.
In their study, Durbin and colleagues wrote that because immunity to a single dengue virus serotype and/or “waning or unbalanced immune response” to either a natural infection or inadequate vaccination can be risk factors for more severe disease later on, “an effective and safe DENV vaccine needs to simultaneously induce long-lived protective immunity against all DENV serotypes.”
In that landscape, Durbin and colleagues provided further evidence of the potential efficacy of the TV003 vaccine, according to Rothman and Ennis.
“The article by Durbin [and colleagues] shows convincing, robust antibody responses to all four serotypes of DENV after a single dose of a candidate live-attenuated vaccine,” Rothman and Ennis wrote. “These are promising results in the search for a safe and effective dengue vaccine for general use in dengue endemic areas. Long-term safety and efficacy data will be awaited with interest.” – by Gerard Gallagher
Disclosure: Rothman reports receiving compensation from Sanofi Pasteur as a scientific advisory board member for the dengue vaccine program. All other researchers report no relevant financial disclosures.