TV003 / Medigen Biotech, National Institute of Allergy and Infectious Diseases, Butantan Institute - LARVOL DELTA

Dengue Vaccines in a Changing Epidemiological Landscape: Current Evidence, Unresolved Challenges, and Public Health Considerations. (PubMed, Vaccines (Basel)) - "Dengue vaccination should be integrated with surveillance, vector control, clinical preparedness, and risk communication. Population-based vaccination is most appropriate in high-transmission settings, whereas selective, risk-based strategies are preferable in temperate regions. Continued pharmacovigilance and effectiveness monitoring are essential to guide safe and equitable implementation."

Journal • Review • Dengue Fever • Infectious Disease

Dengue Vodcast: Insights from Recent Infectious Disease Congresses. (PubMed, Infect Dis Ther) - "They also highlight the need for an integrated approach to targeting dengue, bringing together advanced diagnostic and prognostic tools, vector control techniques, and novel therapeutic and disease management strategies.Vodcast available for this article. Podcast Audio (MP4 1271498 KB)."

Journal • Review • Dengue Fever • Infectious Disease • Pediatrics

Update on efficacy, safety, and immunogenicity of Dengue vaccines: a systematic review and meta-analysis. (PubMed, Infez Med) - "Chimeric Yellow Fever-Dengue Tetravalent Vaccine (CYD-TDV/Dengvaxia®) was assessed in 28 trials, 3 of which reported a pooled vaccine efficacy of 55% (95%CI 47%-62, I 2=86.9%; p <0.001) against Dengue...Takeda-003 (TAK-003/QDENGA®) was evaluated in 23 trials, showing sustained efficacy against virologically confirmed dengue (43.5%-82.1%) and high protection against hospitalization (approximately 87%-90%)...Other promising candidates included other investigational vaccines such as subunit (V180) or DNA-based (TVDV, D1ME100)...Emerging vaccine candidates, including TV003/TV005, Butantan-DV, TDEN, inactivated, subunit, and DNA-based platforms, have also shown promising safety and immunogenicity results in early-phase trials. Future attempts should focus on developing Dengue vaccines that provide safe, balanced, and durable protection against all four Dengue virus serotypes while minimizing the risk of antibody-dependent enhancement, focusing also on special..."

Journal • Retrospective data • Review • Dengue Fever • Infectious Disease

The Power of Public Science: Lessons from TV003 and Butantan-DV. (PubMed, J Infect Dis) - No abstract available

Journal • Dengue Fever

Phase 3b Trial To Evaluate Safety And Immune Response (Superiority) of a Two-Dose Butantan-DV Regimen And The Standard Single Dose In Dengue-Naive Children/Adolescents and Immune Response (Non-inferiority) in a Manufacturing Facility Change (DEN-06-IB) (clinicaltrials.gov) - P3 | N=1765 | Not yet recruiting | Sponsor: Butantan Institute

Head-to-Head • New P3 trial • Dengue Fever

Butantan-DV Vaccine in Elderly Populations (DEN-04-IB) (clinicaltrials.gov) - P3 | N=997 | Recruiting | Sponsor: Butantan Institute | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Aug 2026 ➔ Mar 2027

Head-to-Head • Trial completion date • Trial primary completion date • Dengue Fever

Safety and Immunogenicity of the Live-Attenuated Quadrivalent Dengue Vaccine V181 Compared With Butantan-DV Among Healthy Adults in Brazil: A Randomized, Double-Blind, Phase 2 Trial. (PubMed, Clin Infect Dis) - P2 | "V181 was immunogenic in adults, and while immunogenicity was noninferior to Butantan-DV for DENV-1 and DENV-2, seroconversion rates were noninferior for DENV-1 to DENV-4. The safety profile of V181 is comparable to that of Butantan-DV and supports its continued evaluation as a single-dose quadrivalent vaccine for dengue prevention."

Clinical • Journal • P2 data • Dengue Fever • Infectious Disease

Benign maculopapular rash following dengue vaccination with Butantan-DV: a case series. (PubMed, An Bras Dermatol) - No abstract available

Journal • Dengue Fever

Dengue and chikungunya vaccines past, present and future: implications for travelers. (PubMed, Curr Opin Infect Dis) - "Dengue and chikungunya vaccines are increasingly being used in immunization programs and pretravel consultations. Further real-world data are needed-particularly for seronegative dengue vaccine recipients and older, immunocompromised or medically at-risk adults. Research priorities include developing single-dose, nonlive dengue vaccines suitable for high-risk groups, understanding long-term chikungunya vaccine performance, and exploring broader flaviviral or pan-arboviral platforms."

Journal • Chikungunya • Dengue Fever • Infectious Disease

SAFE-BDVARD: Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases (clinicaltrials.gov) - P4 | N=477 | Recruiting | Sponsor: University of Sao Paulo General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Ankylosing Spondylitis • Dengue Fever • Genetic Disorders • Hematological Disorders • Idiopathic Arthritis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Psoriatic Arthritis • Rare Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Spondylarthritis • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

Evaluation of the Protective Efficacy of TV003 or Previous Zika Infection Against Infection With ZIKV-SJRP Challenge Compared to DENV and ZIKV-naïve Controls Against Infection With ZIKV-SJRP Challenge (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Completed

Trial completion • Dengue Fever • Infectious Disease

Butantan-DV Vaccine in Elderly Populations (DEN-04-IB) (clinicaltrials.gov) - P3 | N=997 | Recruiting | Sponsor: Butantan Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Dengue Fever

Long-term efficacy and safety of the single-dose tetravalent Butantan dengue vaccine. (PubMed, Nat Med) - P3 | "The proportions of participants with unsolicited vaccine-related AEs (including serious AEs) were comparable between intervention groups. A single dose of Butantan-DV was efficacious against symptomatic virologically confirmed dengue because of DENV-1 or DENV-2, regardless of dengue serostatus at baseline, with no safety concerns observed during the 5-year follow-up (ClinicalTrials.gov: NCT02406729 )."

Journal • Dengue Fever • Infectious Disease • Pain

Animal Models Illuminate Dengue Immunopathogenesis to Guide Vaccine and Therapeutic Developments. (PubMed, J Virol Methods) - "The protection provided by the monoclonal antibody C10 was shown to mitigate antibody-dependent enhancement (ADE) in murine models, though it is not associated with the Dengvaxia vaccine. The further development of these animal models will be necessary to expedite the safe development of next-generation dengue vaccines (TAK-003, TV003/TV005), antivirals (favipiravir, sofosbuvir), and immune modulators (IL-6 and TNF-α blockers) for use in endemic areas."

Journal • Preclinical • Review • Dengue Fever • Hematological Disorders • Infectious Disease • Obesity • IFNAR2 • IL1B • IL6

Barriers to dengue vaccine coverage in low- and middle-income countries (LMICs). (PubMed, Virology) - "Dengvaxia (CYD-TDV) and Qdenga (TAK-003) are the only two licensed dengue vaccines currently available, while Butantan-DV (TV003) is an advanced candidate with promising Phase 3 clinical trial results...We therefore identify several state and market-driven systemic factors, as well as declining vaccine confidence, as barriers to scaling up dengue vaccine access in LMICs. These barriers must be addressed through creative solutions to ensure the equitable distribution of dengue vaccines to the populations and countries that need them the most."

Journal • Review • Dengue Fever • Infectious Disease

Current status of dengue fever epidemics and vaccine development. (PubMed, Virol Sin) - "To date, two vaccines-Dengvaxia and Qdenga-have been licensed for clinical use. Six other vaccine candidates are currently in clinical trials, among which the tetravalent live-attenuated vaccines TV003/TV005 are considered the most promising. Despite considerable advances in dengue vaccine research, significant challenges remain, including the need to elicit balanced immune responses against the four serotypes and to reduce the risk of antibody-dependent enhancement (ADE). Taken together, this review systematically summarizes recent global and regional trends in dengue fever and the current progress in dengue vaccine development, collectively offering a valuable resource for informing prevention and control strategies."

Journal • Review • Dengue Fever • Infectious Disease

SAFE-BDVARD: Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases (clinicaltrials.gov) - P4 | N=477 | Not yet recruiting | Sponsor: University of Sao Paulo General Hospital | Phase classification: P3 ➔ P4

Phase classification • Ankylosing Spondylitis • Dengue Fever • Genetic Disorders • Hematological Disorders • Idiopathic Arthritis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Psoriatic Arthritis • Rare Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Spondylarthritis • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

Immunogenicity and safety of tetravalent dengue vaccines: a systematic review of clinical trials. (PubMed, Gac Med Mex) - "The studies evaluated outcomes such as the incidence of severe dengue, seropositivity, and immune response to the vaccines TV003 and TV005. Tetravalent vaccines show a promising outlook in reducing the incidence of severe dengue, although limitations were identified in study designs and heterogeneity in the studied populations. Further research is needed to confirm efficacy and safety in diverse populations."

Clinical • Journal • Review • Dengue Fever

Butantan-DV Vaccine in Elderly Populations (DEN-04-IB) (clinicaltrials.gov) - P3 | N=997 | Not yet recruiting | Sponsor: Butantan Institute | Initiation date: Jul 2025 ➔ Nov 2025

Head-to-Head • Trial initiation date • Dengue Fever

SAFE-BDVARD: Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases (clinicaltrials.gov) - P3 | N=477 | Not yet recruiting | Sponsor: University of Sao Paulo General Hospital | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • Ankylosing Spondylitis • Dengue Fever • Genetic Disorders • Hematological Disorders • Idiopathic Arthritis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Psoriatic Arthritis • Rare Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Spondylarthritis • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

Efficacy of the live attenuated tetravalent dengue vaccine TV003 or previous Zika infection against Zika challenge (ASTMH 2025) - "Previous ZIKV infection imparted complete protection against ZIKV challenge 9/10 volunteers. One volunteer who was enrolled based on ZIKV seropositivity was not protected against ZIKV challenge. The efficacy of TV003 against ZIKV challenge at 6 months will also be presented."

Clinical • Dengue Fever • Infectious Disease

Five-Year Efficacy and Safety of a Live, Attenuated Tetravalent Dengue Vaccine Produced by Instituto Butantan: Results from a Phase 3 Clinical Trial in Children, Adolescents, and Adults (ASTMH 2025) - P3 | "VE [95%CI] against dengue with warning signs/severe dengue was 80.5% [50.8-92.4%]. In summary, Butantan-DV remained efficacious against symptomatic VCD due to DENV-1 or DENV-2, regardless of dengue serostatus at baseline, with no safety concerns observed during the entire five-year follow-up."

Clinical • P3 data • Dengue Fever

Randomized, double-blind, placebo-controlled, phase 3 trial to demonstrate lot-to-lot consistency of 3 lots of the simplified formulation of Butantan-dengue vaccine. (PubMed, Vaccine) - P3 | "Three lots of simplified formulation were safe and achieved the endpoint of equivalence of lots."

Clinical • Journal • P3 data • Allergy • Dengue Fever • Immunology • Infectious Disease

SAFE-BDVARD: Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases (clinicaltrials.gov) - P3 | N=477 | Not yet recruiting | Sponsor: University of Sao Paulo General Hospital | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Aug 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Dengue Fever • Genetic Disorders • Hematological Disorders • Idiopathic Arthritis • Immunology • Inflammatory Arthritis • Lupus • Myositis • Psoriatic Arthritis • Rare Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Spondylarthritis • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

State of the Art on Vaccine Development Against Dengue Infection: Scoping Review of the Literature. (PubMed, Infect Dis Rep) - "Vaccines were categorized into licensed (CYD-TDV and TAK-003), late-stage (TV003/TV005), and early-stage candidates (TDEN, DPIV, V180, TVDV)...TAK-003 (Qdenga®) demonstrated high efficacy against virologically confirmed dengue (VCD) and dengue-related hospitalization...Currently, TAK-003 is regarded as the best option for broad implementation, while TV003 and TV005 remain promising candidates due to their shorter schedule and robust immunogenicity. Further research is needed to optimize vaccine strategies in seronegative populations, immunocompromised subjects, older adults, and travelers."

Journal • Review • Dengue Fever • Infectious Disease