Novel vaccine effective in people without prior dengueFebruary 5, 2020
A novel tetravalent dengue vaccine candidate developed by Takeda is found demonstrating similar degrees of protection in individuals who had and had not been previously infected with dengue.
The TAK-003 vaccine candidate, however, failed to protect against one type of the virus in people with no prior exposure to dengue.
The vaccine showed 80.2% effectiveness at preventing dengue among children and teens in the year after they got the shot, according to the Tetravalent Immunization against Dengue Efficacy Study (TIDES)study, published in the New England Journal of Medicine.
For the study, children and adolescents aged 4 to 16 years were randomly assigned in a ratio 2:1 to receive two doses of vaccine or placebo 3 months apart. The participants were tested for virologically confirmed dengue by a serotype-specific reverse-transcriptase polymerase chain reaction. The primary endpoint was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype.
Of the 20,071 participants who were given at least one dose of vaccine or placebo, 19,021 (94.8%) received both injections and were included in the per-protocol analysis.
The overall vaccine efficacy in the safety population was 80.9% (78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group).
In the per-protocol analyses, vaccine efficacy was 80.2% (61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalisation (5 hospitalisations in the vaccine group vs. 53 hospitalisations in the placebo group).
Planned exploratory analyses involving 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group).
Lack of efficacy on serotype 3
Dengue virus infections caused by all four serotypes were observed in the global TIDES trial. Exploratory analyses of secondary endpoints showed efficacy varied by serotype: VE was 73.7% for serotype 1 (95% CI: 51.7% to 85.7%), 97.7% for serotype 2 (95% CI: 92.7% to 99.3%), and 62.6% for serotype 3 (95% CI: 43.3% to 75.4%). There were too few dengue serotype 4 virus cases to fully assess efficacy at this time (VE: 63.2% [95% CI: -64.6% to 91.8%]).
Further analyses of exploratory endpoints also showed that, for both serotypes 1 and 2, efficacy levels among seropositives and seronegatives were similar. For dengue serotype 3, VE in baseline seropositives was 71.3% (95% CI: 54.2% to 82.0%), and in seronegatives, results were inconclusive but suggested a lack of efficacy (VE: -38.7% [95% CI: –335.7% to 55.8%]). No dengue serotype 4 cases were observed in seronegative participants.
The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively).
Historically, vaccine development against dengue has been challenging, especially for people who haven’t previously been exposed to dengue, and these results demonstrate protection from dengue fever, including among many participants without prior dengue. Takeda said in a statement.
Dengvaxia- Low on seronegatives
Currently, Dengvaxia (CYD-TDV), developed by Sanofi Pasteur, is the first and only dengue vaccine licensed for use. CYD-TDV is a live recombinant tetravalent dengue vaccine given as a 3-dose series on a 0/6/12-month schedule.
Long-term safety follow-up, however, indicated that the vaccine performs differently in seropositive versus seronegative individuals.
Vaccine efficacy (VE) against virologically confirmed symptomatic dengue was high among inferred baseline seropositive participants =9 years of age: 76% (95%CI: 63.9, to 84.0), but much lower among baseline seronegative participants: 38.8% (95%CI: –0.9 to 62.9%) in the first 25 months after the first dose of vaccine.
A mosquito-borne viral infection causing severe flu-like illness and, sometimes causing a potentially lethal complication, dengue is a fast-emerging pandemic-prone viral disease in many parts of the world.