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. 2021 Jun 11:45:e67.
doi: 10.26633/RPSP.2021.67. eCollection 2021.

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

Shibadas Biswal  1 , Jorge Fernando Mendez Galvan  2 , Mercedes Macias Parra  3 , Juan-Francisco Galan-Herrera  4 , Monica Belisa Carrascal Rodriguez  5 , Esteban Patricio Rodriguez Bueno  6 , Manja Brose  7 , Martina Rauscher  7 , Inge LeFevre  7 , Derek Wallace  1 , Astrid Borkowski  7
Affiliations

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

Shibadas Biswal et al. Rev Panam Salud Publica. .

Abstract
in English, Spanish, Portuguese

Objective: To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637).

Methods: Participants aged 12-17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study.

Results: 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis).

Conclusion: TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Objetivo: Describir la inmunogenicidad y la seguridad de una vacuna tetravalente contra el dengue (TAK-003) en adolescentes sanos residentes en Ciudad de México, considerada un área no endémica de dengue (NCT03341637).

Métodos: Se asignó de manera aleatoria a un grupo de participantes de 12 a 17 años en una proporción 3:1 para que recibieran dos dosis (en el mes 0 y en el mes 3) de la vacuna TAK-003 o de un placebo. Se evaluó la inmunogenicidad mediante un análisis de microneutralización de anticuerpos neutralizantes del virus del dengue al inicio del estudio y en los meses 4 y 9. Se registraron los eventos adversos de notificación solicitada y los referidos por iniciativa propia después de cada vacunación. A lo largo del estudio se registraron los eventos adversos graves y los que requirieron atención médica.

Resultados: Participaron 400 adolescentes y 391 (97,8%) finalizaron el estudio. 36 adolescentes (9%) fueron seropositivos a ≥1 serotipos (título recíproco ≥10) al inicio del estudio. La media geométrica de los títulos en las personas seronegativas vacunadas con TAK-003 al inicio del estudio fue de 328, 1743, 120 y 143 en el mes 4 y 135, 741, 46 y 38 en el mes 9 en relación con DENV-1, -2, -3 y -4, respectivamente. La media geométrica de los títulos de las personas que recibieron un placebo se mantuvo en <10. Las tasas de seropositividad tetravalente en los vacunados fueron 99,6% y 85,8% a los meses 4 y 9, respectivamente. Se consideró relacionado con el tratamiento un evento adverso con atención médica que tuvo lugar en cada grupo (TAK-003: eritema en el lugar de la inyección; placebo: faringitis).

Conclusiones: TAK-003 fue inmunogénica ante los cuatro serotipos y bien tolerada en los adolescentes sin exposición previa al dengue que vivían en Ciudad de México.

Objetivo: Descrever a imunogenicidade e a segurança de uma vacina tetravalente contra dengue (TAK-003) em adolescentes saudáveis residentes da Cidade do México, área considerada não endêmica para dengue (ClinicalTrials.gov: NCT03341637).

Métodos: Participantes com idade entre 12 e 17 anos foram randomizados a uma proporção de 3:1 para receber duas doses da vacina TAK-003 ou placebo (no mês 0 e no mês 3). A imunogenicidade foi avaliada pelos títulos de anticorpos neutralizantes contra dengue determinados em ensaio de microneutralização ao início do estudo, no mês 4 e no mês 9. A ocorrência de eventos adversos solicitados ou espontâneos foi registrada após cada rodada de vacinação. Eventos adversos graves e eventos adversos que exigiram atendimento médico foram monitorados ao longo de todo o estudo.

Resultados: De 400 adolescentes incluídos na amostra estudada, 391 (97,8%) completaram o estudo. Trinta e seis (9%) apresentaram positividade basal a um ou mais sorotipos virais da dengue (título recíproco ≥10). A média geométrica dos títulos de anticorpos nos vacinados com TAK-003 que eram soronegativos ao início do estudo foi de 328, 1743, 120 e 143 no mês 4 e 135, 741, 46 e 38 no mês 9, contra os sorotipos virais DENV-1, DENV-2, DENV-3 e DENV-4, respectivamente. A média geométrica dos títulos de anticorpos no grupo placebo se manteve abaixo de 10. A taxa de soropositividade tetravalente nos vacinados foi de 99,6% no mês 4 e 85,8% no mês 9. Um único evento adverso que exigiu atendimento médico em cada grupo foi considerado relacionado ao tratamento (eritema no local de aplicação no grupo TAK-003 e faringite no grupo placebo).

Conclusão: A vacina TAK-003 demonstrou ser imunogênica contra os quatro sorotipos virais da dengue e foi bem tolerada em adolescentes residentes da Cidade do México sem história pregressa de infecção pela dengue.

Keywords: Mexico; Vaccines; adolescents; dengue; immunogenicity; safety.

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Figures

FIGURE 1.
FIGURE 1.. Study participation flowchart from screening to study completion, including reasons for non-randomization, discontinuation, and exclusion from the per protocol set
FIGURE 2.
FIGURE 2.. Geometric mean titres (GMTs) of dengue neutralizing antibodies (microneutralization assay) and 95% confidence intervals against each serotype in the study (“current study”), and from seronegative adolescents in Latin America enrolled in a separate phase 3 efficacy study (“Phase 3 efficacy study”). Per protocol set data
FIGURE 3.
FIGURE 3.. Seropositivity rates and 95% confidence intervals of dengue neutralising antibodies (measured by microneutralization assay) against individual and multiple serotypes in the study (“current study”), and in seronegative adolescents in Latin America enrolled in a separate phase 3 efficacy study (“Phase 3 efficacy study”). Per protocol set data
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References

    1. World Health Organization . Geneva: WHO; 2020. [Accessed 05 June 2020]. Urgent health challenges for the next decade [Internet] Available from: https://www.who.int/news-room/photo-story/photo-story-detail/urgent-heal....
    2. 1. World Health Organization. Urgent health challenges for the next decade [Internet]. Geneva: WHO; 2020. Available from: https://www.who.int/news-room/photo-story/photo-story-detail/urgent-heal.... Accessed 05 June 2020.
    1. World Health Organization . Geneva: WHO; 2019. [Accessed 04 November 2019]. Dengue and Severe Dengue Fact Sheet [Internet] Avaliable from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue.
    2. 2. World Health Organization. Dengue and Severe Dengue Fact Sheet [Internet]. Geneva: WHO; 2019. Avaliable from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue. Accessed 04 November 2019.
    1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504–507. doi: 10.1038/nature12060. - DOI - PMC - PubMed
    2. 3. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-7. doi: 10.1038/nature12060. - PMC - PubMed
    1. Wilder-Smith A. Dengue infections in travellers. Paediatr Int Child Health. 2012;32(Suppl 1):28–32. doi: 10.1179/2046904712Z.00000000050. - DOI - PMC - PubMed
    2. 4. Wilder-Smith A. Dengue infections in travellers. Paediatr Int Child Health. 2012;32 Suppl 1:28-32. doi: 10.1179/2046904712Z.00000000050. - PMC - PubMed
    1. Halstead S, Wilder-Smith A. Severe dengue in travellers: pathogenesis, risk and clinical management. J Travel Med. 2019;26(7):taz062. doi: 10.1093/jtm/taz062. - DOI - PubMed
    2. 5. Halstead S, Wilder-Smith A. Severe dengue in travellers: pathogenesis, risk and clinical management. J Travel Med. 2019;26(7):taz062. doi: 10.1093/jtm/taz062. - PubMed

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