{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:36:11Z","timestamp":1786628171343,"version":"build-2736575974"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dengue remains a growing global health threat with no specific antiviral treatment available. TAK-003, a tetravalent live-attenuated vaccine, offers a promising preventive option, particularly for seronegative individuals, necessitating a comprehensive safety evaluation to inform public health strategies.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analysis by searching various indexes and registries up to May 31, 2025. Phase 1\u20133 RCTs comparing TAK-003 with placebo or control vaccines were included. Pooled risk ratios (RRs or odds ratios (ORs with 95% confidence intervals (CIs were calculated; heterogeneity and subgroup analyses were performed. Eighteen clinical trials were included in the systematic review, and 11 clinical trials were included in the meta-analysis. No significant difference emerged in serious adverse events (SAEs (RR: 0.91, 95% CI: 0.55\u20131.50 or mortality (RR: 0.38, 95% CI: 0.04\u20133.92 between TAK-003 and placebo. Local solicited adverse events\u2014especially injection-site pain and redness\u2014were significantly higher with TAK-003 after the first dose (OR: 5.24, 95% CI: 1.02\u2013 27.02. Systemic adverse events like headache and myalgia were also slightly higher in the TAK-003 group after the first dose (OR: 1.48, 95% CI: 1.10\u20131.99 but not after the second. Unsolicited adverse events and pregnancy outcomes were comparable, revealing no new safety concerns. TAK-003 shows an acceptable safety profile, with no rise in SAEs or mortality. Although local and mild systemic reactions were more common, they were brief and tolerable, supporting an acceptable safety profile within the available randomized clinical trial evidence.<\/jats:p>","DOI":"10.4103\/ijcm.ijcm_882_25","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:00:07Z","timestamp":1786604407000},"page":"619-630","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["TAK-003 Dengue Vaccine Safety: Evidence from a Systematic Review and Meta-analysis of Clinical Trials"],"prefix":"10.4103","volume":"51","author":[{"given":"Rajesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Maharshi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, All India Institute of Medical Sciences, Patna, Bihar, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"R2-20260813","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7006a1","article-title":"Dengue vaccine: Recommendations of the Advisory Committee on immunization practices, United States, 2021","volume":"70","author":"Paz-Bailey","year":"2021","journal-title":"MMWR Recomm Rep"},{"key":"R3-20260813","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3390\/diseases12020032","article-title":"Dengue fever epidemics and the prospect of vaccines: A systematic review and meta-analysis using clinical trials in children","volume":"12","author":"Okoye","year":"2024","journal-title":"Diseases"},{"key":"R4-20260813","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S0140-6736(20)30414-1","article-title":"Efficacy of a tetravalent dengue vaccine in healthy children aged 4-16 years: A randomised, placebo-controlled, phase 3 trial","volume":"395","author":"Biswal","year":"2020","journal-title":"Lancet"},{"key":"R5-20260813","doi-asserted-by":"crossref","first-page":"770","DOI":"10.3390\/vaccines12070770","article-title":"Immunogenicity, safety and efficacy of the dengue vaccine TAK-003: A meta-analysis","volume":"12","author":"Flacco","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"R7-20260813","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/S1473-3099(14)70811-4","article-title":"Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: A randomised, placebo-controlled, phase 1 study","volume":"14","author":"Osorio","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"R8-20260813","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1093\/infdis\/jiv179","article-title":"Safety and immunogenicity of a live attenuated tetravalent dengue vaccine candidate in flavivirus-naive adults: A randomized, double-blinded phase 1 clinical trial","volume":"212","author":"George","year":"2015","journal-title":"J Infect Dis"},{"key":"R9-20260813","doi-asserted-by":"crossref","first-page":"6351","DOI":"10.1016\/j.vaccine.2015.09.008","article-title":"Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study","volume":"33","author":"Rupp","year":"2015","journal-title":"Vaccine"},{"key":"R10-20260813","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1093\/infdis\/jiv762","article-title":"Safety and immunogenicity of a tetravalent dengue vaccine 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City","volume":"45","author":"Biswal","year":"2021","journal-title":"Rev Panam Salud Publica"},{"key":"R17-20260813","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1093\/infdis\/jiaa761","article-title":"Efficacy of a dengue vaccine candidate (TAK-003) in healthy children and adolescents 2 years after vaccination","volume":"225","author":"L\u00f3pez-Medina","year":"2022","journal-title":"J Infect Dis"},{"key":"R19-20260813","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1093\/infdis\/jiaa406","article-title":"Long-term safety and immunogenicity of a tetravalent dengue vaccine candidate in children and adults: A randomized, placebo-controlled, phase 2 study","volume":"225","author":"Sirivichayakul","year":"2022","journal-title":"J Infect Dis"},{"key":"R20-20260813","doi-asserted-by":"crossref","first-page":"2254964","DOI":"10.1080\/21645515.2023.2254964","article-title":"An open-label, Phase 3 trial of TAK-003, a live attenuated dengue tetravalent vaccine, in healthy US adults: Immunogenicity and safety when administered during the second half of a 24-month shelf-life","volume":"19","author":"Patel","year":"2023","journal-title":"Hum Vaccin Immunother"},{"key":"R21-20260813","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.vaccine.2023.01.007","article-title":"A randomized phase 3 trial of the immunogenicity and safety of coadministration of a live-attenuated tetravalent dengue vaccine (TAK-003) and an inactivated hepatitis a (HAV) virus vaccine in a dengue non-endemic country","volume":"41","author":"Tricou","year":"2023","journal-title":"Vaccine"},{"key":"R22-20260813","doi-asserted-by":"crossref","first-page":"e0011124","DOI":"10.1371\/journal.pntd.0011124","article-title":"Immunogenicity and safety of concomitant and sequential administration of yellow fever YF-17D vaccine and tetravalent dengue vaccine candidate TAK-003: A phase 3 randomized, controlled 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