BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS
Intro: Dengue efficacy studies are not feasible in dengue non-endemic countries. For TAK-003, we present an immunobridging analysis to infer vaccine efficacy as determined in the DEN-301 phase 3 efficacy trial conducted in children and adolescents from eight dengue-endemic countries to adults from n...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | International Journal of Infectious Diseases |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971223001571 |
| _version_ | 1827945276236627968 |
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| author | C. Halim V. Tricou F. Nordio N. Folschweiller |
| author_facet | C. Halim V. Tricou F. Nordio N. Folschweiller |
| author_sort | C. Halim |
| collection | DOAJ |
| description | Intro: Dengue efficacy studies are not feasible in dengue non-endemic countries. For TAK-003, we present an immunobridging analysis to infer vaccine efficacy as determined in the DEN-301 phase 3 efficacy trial conducted in children and adolescents from eight dengue-endemic countries to adults from non-endemic areas of the USA enrolled in the phase 3 immunogenicity DEN-304 trial. Methods: Children and adolescents aged 4–16 years received two doses of TAK-003 or placebo at Months 0 and 3 in DEN-301 (NCT02747927). In DEN-304 (NCT03423173), adults aged 18–60 years received two doses of TAK-003 or placebo at Months 0 and 3. Geometric mean titers (GMTs) of dengue-neutralizing antibodies were assessed via a validated microneutralization assay; a comparison of GMTs showed non-inferiority for individual serotypes if the upper bound of the 95% CI for the geometric mean ratio (GMR) between the two groups was <2.0. Seropositivity rate was defined as the proportion of participants with post-vaccination reciprocal MNT50 titers ≥10. Findings: Overall, 1,081 baseline-seronegative participants were included in this analysis (702 children/adolescents and 379 adults). At Month 4, noninferiority of immunogenicity was shown for dengue virus (DENV)-1, -2, and -4, but marginally missed for DENV-3 with a GMR (95% CI) of 1.77 (1.53, 2.04) (GMT [95% CI]: adults, 128.9 [115.0, 144.4]; children/adolescents, 228.0 [209.2, 248.5]). By Month 9, non-inferiority was shown for all four serotypes. Seropositivity rates against individual serotypes ranged from 92% to 100% at Months 4 and 9. Similar levels of response were also observed in a number of additional exploratory assessments of the humoral immune response. Conclusion: The analysis shows comparable immune response to TAK-003 in baseline-seronegative adults as in children/adolescents, supporting extrapolation of the efficacy profile of TAK-003 to adults. |
| first_indexed | 2024-03-13T10:41:17Z |
| format | Article |
| id | doaj.art-b45b04cb0c84455e82d7f260e900355e |
| institution | Directory Open Access Journal |
| issn | 1201-9712 |
| language | English |
| last_indexed | 2024-03-13T10:41:17Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Infectious Diseases |
| spelling | doaj.art-b45b04cb0c84455e82d7f260e900355e2023-05-18T04:37:58ZengElsevierInternational Journal of Infectious Diseases1201-97122023-05-01130S10BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTSC. Halim0V. Tricou1F. Nordio2N. Folschweiller3Takeda Indonesia, Medical Affairs, Jakarta, IndonesiaTakeda Pharmaceuticals International AG, Vaccines Business Unit, Zürich, SwitzerlandTakeda Vaccines, Inc., Statistics and Quantitative Sciences (SQS), Cambridge, MA, United States of AmericaTakeda Pharmaceuticals International AG, Vaccines Business Unit, Zürich, SwitzerlandIntro: Dengue efficacy studies are not feasible in dengue non-endemic countries. For TAK-003, we present an immunobridging analysis to infer vaccine efficacy as determined in the DEN-301 phase 3 efficacy trial conducted in children and adolescents from eight dengue-endemic countries to adults from non-endemic areas of the USA enrolled in the phase 3 immunogenicity DEN-304 trial. Methods: Children and adolescents aged 4–16 years received two doses of TAK-003 or placebo at Months 0 and 3 in DEN-301 (NCT02747927). In DEN-304 (NCT03423173), adults aged 18–60 years received two doses of TAK-003 or placebo at Months 0 and 3. Geometric mean titers (GMTs) of dengue-neutralizing antibodies were assessed via a validated microneutralization assay; a comparison of GMTs showed non-inferiority for individual serotypes if the upper bound of the 95% CI for the geometric mean ratio (GMR) between the two groups was <2.0. Seropositivity rate was defined as the proportion of participants with post-vaccination reciprocal MNT50 titers ≥10. Findings: Overall, 1,081 baseline-seronegative participants were included in this analysis (702 children/adolescents and 379 adults). At Month 4, noninferiority of immunogenicity was shown for dengue virus (DENV)-1, -2, and -4, but marginally missed for DENV-3 with a GMR (95% CI) of 1.77 (1.53, 2.04) (GMT [95% CI]: adults, 128.9 [115.0, 144.4]; children/adolescents, 228.0 [209.2, 248.5]). By Month 9, non-inferiority was shown for all four serotypes. Seropositivity rates against individual serotypes ranged from 92% to 100% at Months 4 and 9. Similar levels of response were also observed in a number of additional exploratory assessments of the humoral immune response. Conclusion: The analysis shows comparable immune response to TAK-003 in baseline-seronegative adults as in children/adolescents, supporting extrapolation of the efficacy profile of TAK-003 to adults.http://www.sciencedirect.com/science/article/pii/S1201971223001571 |
| spellingShingle | C. Halim V. Tricou F. Nordio N. Folschweiller BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS International Journal of Infectious Diseases |
| title | BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS |
| title_full | BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS |
| title_fullStr | BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS |
| title_full_unstemmed | BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS |
| title_short | BRIDGING THE IMMUNOGENICITY OF A TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) FROM CHILDREN AND ADOLESCENTS TO ADULTS |
| title_sort | bridging the immunogenicity of a tetravalent dengue vaccine candidate tak 003 from children and adolescents to adults |
| url | http://www.sciencedirect.com/science/article/pii/S1201971223001571 |
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