Butantan-DV Dengue Vaccine Clinical Trials, Dosage, Indication, News, Side Effects

Butantan Institute's single-dose, tetravalent, live, attenuated Butantan-DV Dengue Vaccine is conducting phase 3 clinical trials as of September 2024. Butantan-DV contains genetically attenuated versions of all four dengue virus serotypes. The attenuated dengue vaccine results from a partnership between Butantan, the U.S. National Institutes of Health (NIH), and the American Type Culture Archive (ATCC). Development of the tetravalent dengue vaccine began at Butantan Institute in 2010 with FAPESP's support, using a formulation created by researchers affiliated with the NIH.

Butantan-DV is a cocktail of four live-attenuated dengue viruses (DENVs). However, three dengue serotypes are near full-length DENV genomes, whereas only one component (DENV-2) is a chimeric vaccine virus. This chimeric virus contains two structural genes of DENV-2 on the same attenuated DENV-4 genetic background as the DENV-4 component of the vaccine. Consequently, Butantan-DV contains more homologous immunogenic dengue proteins for each serotype in the cocktail (including non-structural proteins for three of the four serotypes) than the other two highly chimeric vaccines.

Human phase 1 clinical trials in Brazil started in 2013, with the support of the Butantan Foundation and Brazil's national development bank, BNDES. The ongoing Phase 3 clinical trial results showed in an article published by The Lancet on August 5, 2024, that the vaccine is safe and 79.6% effective for all age groups between 2 and 59 and people with or without a prior history of infection by dengue virus. A phase 3 study funded by Instituto Butantan and others published an Original Article in the NEJM that found a single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up.

Instituto Butantan is the leading producer of immunobiologicals (vaccines) in Brazil. 

Butantan-DV Dengue Vaccine Availability 2024

Butantan Institute plans to submit a report to Brazil's health surveillance agency (ANVISA) in 2024, applying for the vaccine's registration. 

Butantan-DV Dengue Vaccine Dosage

Butantan-DV Dengue Vaccine is a single dose administration.

Butantan-DV Dengue Vaccine Indication

Butantan-DV Dengue Vaccine offers people protection against four types of the dengue virus.

Butantan-DV Dengue Vaccine Side Effects

In a phase 3 study, solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants vs. 45.6%).

Butantan-DV Dengue Vaccine News

August 5, 2024 - A Commentary published by The Lancet Infectious Disease highlighted the Butantan-DV vaccine's potential.

February 1, 2024 - The New England Journal of Medicine published Phase 3 clinical trial data. The dengue vaccine is safe for participants who have had dengue and those who have never been exposed to the virus before. “Findings from Phase 2 [the previous clinical trial] showed that the four attenuated viral serotypes in Butantan-DV multiply in the human organism and induce a balanced response in terms of antibody production. This leads us to conclude that its efficacy against DENV-3 and DENV-4 will also be good,” said virologist Maurício Lacerda Nogueira.

December 16, 2022 - The Butantan-DV dengue vaccine under development by the Butantan Institute shows 79.6% overall efficacy to prevent the disease, according to initial phase 3 clinical study results. During the two-year follow-up of the volunteers, there were no cases of severe dengue fever or alarm signs.

Butantan-DV Dengue Vaccine Clinical Trials

ClinicalTrials.gov ID NCT02406729 - Phase III, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Immunogenicity of the Dengue 1, 2, 3, 4 (Attenuated) Vaccine From Instituto Butantan. This randomized, multicenter, double-blind, placebo-controlled Phase III study will evaluate the efficacy and safety of a live attenuated, tetravalent, lyophilized dengue vaccine produced by the Butantan Institute. Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or a placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) — 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0), and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period.

ClinicalTrials.gov ID NCT01696422 - This is a phase II step-wise, randomized, multicenter, double-blind, and controlled clinical trial to evaluate the safety and immunogenicity of an attenuated tetravalent lyophilized dengue vaccine manufactured by Butantan Institute. Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received a placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received a placebo. Butantan-DV and TV003 were immunogenic and well-tolerated; no severe adverse reactions were observed. In step A, the rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4.