Long-Term Safety and Antibody Persistence of TDV and the Impact of a Booster Dose

Takeda365 enrolled

Overview

The purpose of this study is to describe antibody persistence for each of the 4 dengue serotypes for up to 63 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-315 (NCT03341637) (Mexico) and for up to 36 months after the first vaccination in the primary vaccination series for participants from parent trial DEN-304 (NCT03423173) (United States \[US\]) and to describe the impact of a tetravalent dengue vaccine (TDV) booster dose vs placebo on antibody response for each of the 4 dengue serotypes at 1 month and 6 months post administration of the TDV booster or placebo.

The vaccine tested in this study is Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV). This study will look at the long-term antibody persistence and safety of Takeda's TDV in healthy adolescents and adults and will assess the impact of a booster dose. The study has enrolled 365 healthy participants. Participants who previously received TDV in two parent trials (DEN-304 \[NCT03423173\] and DEN-315 \[NCT03341637\]), will be invited to participate in this follow-up trial. Participants will be assessed for antibody persistence and safety from Baseline (Month 0) through Month 15 (for participants from parent trial DEN-304 \[US\]) or Month 42 (for participants from parent trial DEN-315 \[Mexico\]). At Month 15 (for participants from parent trial DEN-304 \[US\]) or at Month 42 (for participants from parent trial DEN-315 \[Mexico\]), eligible participants will be randomized in 1:1 ratio to one of two trial groups to receive TDV or placebo: A. Group 1- TDV 0.5 mL subcutaneous (SC) injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico\]). B. Group 2- Takeda's tetravalent dengue placebo (dummy SC injection - this is a liquid that looks like the study drug but has no active ingredient), 0.5 mL, subcutaneous injection at Month 15 for participants from parent trial DEN-304 (US) or at Month 42 for participants from parent trial DEN-315 (Mexico). This multi-centre trial will be conducted in US and Mexico. The overall time to participate in this study is up to 21 months for parent trial DEN-304 (US) and up to 48 months for parent trial DEN-315 (Mexico). Participants from parent trial DEN-304 (US) and participants from parent trial DEN-315 (Mexico) will come for 5 visits to the clinic which includes a final visit (Visit 5) 6 months after the booster dose for a follow-up assessment.

Study Type

INTERVENTIONAL

Allocation

Conditions

Dengue Fever

Interventions

Takeda's Dengue Tetravalent Vaccine (Live, Attenuated) (TDV)BIOLOGICAL

TDV subcutaneous injection

PlaceboBIOLOGICAL

Normal Saline (0.9% NaCl) subcutaneous injection

Eligibility

Sex: ALLMin age: 13 YearsMax age: 63 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1\. Male or female participants (irrespective of serostatus at baseline in the parent trials (DEN-304 \[(NCT03423173)\] and DEN-315 \[NCT03341637\]) who received at least one dose of Takeda's tetravalent dengue vaccine candidate (TDV) in the parent trials and have data from at least one blood draw post-vaccination. Exclusion Criteria: 1. Participants with a prolonged period of habitation (≥1 year) in a dengue endemic area within the 2 years prior to Visit 1 Day 1 (Month 0). 2. Previous and planned vaccination (during the trial conduct), against any flavivirus including dengue (other than Takeda's TDV), yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis. Booster Exclusion Criteria: 1. Participants for whom baseline serostatus is not defined in the parent trials (DEN-304 \[(NCT03423173)\] and DEN-315 \[NCT03341637\]). 2. Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome). 3. Known or suspected impairment/alteration of immune function, including: 1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); use of inhaled, intranasal, or topical corticosteroids is allowed. 2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US). 3. Administration of immunoglobulins and/or any blood products within the 3 months prior to administration of the TDV booster or placebo at Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US); consider whether applicable as an exclusion criterion or criterion for delay. 4. Receipt of immunostimulants within 60 days prior to Month 42 for participants from parent trial DEN-315 (Mexico)/ Month 15 for participants from parent trial DEN-304 (US). 5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Month 42 for participants from parent trial DEN-315 (Mexico) / Month 15 for participants from parent trial DEN-304 (US). 6. Known human immunodeficiency virus (HIV) infection or HIV-related disease. 7. Hepatitis C virus infection. 8. Genetic immunodeficiency. 4. Abnormalities of splenic or thymic function. 5. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 6. Participants with history of current or previous infection with a flavivirus such as dengue, Zika, YF, JE, West Nile fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a prolonged period of habitation (≥1 year) in a dengue endemic area during trial conduct.

Locations (10)

AES - DRS - Optimal Research Alabama - Huntsville

Huntsville, Alabama, United States

AES - DRS - Optimal Research Illinois - Peoria

Peoria, Illinois, United States

Alliance for Multispecialty Research, LLC - Newton - PPDS

Newton, Kansas, United States

Outcomes

Primary Outcomes

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])

GMTs of neutralizing antibodies were measured by microneutralization test 50% (MNT50) for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 0 (Day 1)

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 12

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Time frame: Month 15 (DEN-304)

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.

Time frame: Month 42 (DEN-315)

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1])

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Data from ClinicalTrials.gov

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Optima Research

Rockville, Maryland, United States

AES - DRS - Synexus Clinical Research US, Inc. Minneapolis

Richfield, Minnesota, United States

AES - DRS - Synexus Clinical Research US, Inc. - St. Louis

St Louis, Missouri, United States

AES - DRS - Synexus Clinical Research US, Inc. - Omaha

Papillion, Nebraska, United States

Advanced Clinical Research/Velocity Clinical Research

West Jordan, Utah, United States

Instituto Nacional de Pediatria

Mexico City, Mexico

CAIMED Investigacion en Salud S.A de C.V.

Mexico City, Mexico

Time frame: Month 0 [Day 1)

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 12

Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Time frame: Month 15 (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3 at Month 42 for participants from parent trial DEN-315.

Time frame: Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 0 (Day 1)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 12

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)

Seropositivity Rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Time frame: Month 15 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Time frame: Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 [Month 0 (Day 1])

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 1 at Month 0 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 0 (Day 1)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for participants from both parent trials (DEN-304 and DEN-315).

Time frame: Month 12

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for participants from parent trial DEN-304.

Time frame: Month 15 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) ((DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 42 for parent trial DEN-315.

Time frame: Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 1 (Month 0 [Day 1])

Time frame: Month 0 (Day 1)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 2 (Month 12)

Time frame: Month 12

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 15) (DEN-304)

Time frame: Month 15 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster at Visit 3 (Month 42) (DEN-315)

Time frame: Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 1 (Month 0 [Day 1])

Time frame: Month 0 (Day 1)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 2 (Month 12)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 2 at Month 12 for both parent trials (DEN-304 and DEN-315).

Time frame: Month 12

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. (DEN-304). All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3 at Month 15 for parent trial DEN-304.

Time frame: Month 15 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes in the Period Prior to Booster by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)

Time frame: Month 42 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5, 6 months post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Time frame: 1 month post-booster dose at Month 16 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Time frame: 6 months post-booster dose at Month 48 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Time frame: 1 month post-booster dose at Month 16 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)

GMTs of neutralizing antibodies were measured by MNT50 for each of the 4 Dengue Serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Time frame: 6 months post-booster dose at Month 48 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Time frame: 1 month post-booster dose at Month 16 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Time frame: 6 months post-booster dose at Month 48 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Time frame: 1 month post-booster dose at Month 16 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

Seropositivity Rate for Each of the 4 Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

Seropositivity Rate for Each of the 4 Dengue Serotypes at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)

Seropositivity rate, defined as the percentage of participants seropositive, is derived from the titers of dengue-neutralizing antibodies. Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Time frame: 6 months post-booster dose at Month 48 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 15) (DEN-304)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose at Visit 4 (Month 16) (DEN-304)

Time frame: 1 month post-booster dose at Month 16 (DEN-304.)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 21) (DEN-304)

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose at Visit 3 (Month 42) (DEN-315)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 1 Month Post-Booster Dose at Visit 4 (Month 43) (DEN-315)

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose at Visit 5 (Month 48) (DEN-315)

Time frame: 6 months post-Booster dose at Month 48 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \\ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 3, pre-booster dose for all participants (Month 15 for parent trial DEN-304 and Month 42 for parent trial DEN-315). Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \\ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4, 1 month post-booster dose for all participants (Month 16 for parent trial DEN-304 and Month 43 for parent trial DEN-315).

Time frame: 1 month post-booster dose at Month 16 (DEN-304) and Month 43 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 for Both Parent Trials

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5, 6 month post-booster dose for all participants (Month 21 for parent trial DEN-304 and Month 48 for parent trial DEN-315).

Time frame: 6 months post-booster dose at Month 21 (DEN-304) and Month 48 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 15) (DEN-304)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \\ any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 15 for participants from parent trial DEN-304. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 15 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 16) (DEN-304)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), \\any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 16 for participants from parent trial DEN-304.

Time frame: 1 month post-booster dose at Month 16 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-Booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 21) (DEN-304)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 21 for participants from parent trial DEN-304.

Time frame: 6 months post-booster dose at Month 21 (DEN-304)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at Pre-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 3 (Month 42) (DEN-315)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the pre-booster data from Visit 3 at Month 42 for participants from parent trial DEN-315. Pre-booster dose is defined as the last non-missing value before booster administration.

Time frame: Pre-booster dose at Month 42 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes at 1 Month Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 4 (Month 43) (DEN-315)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 4 at Month 43 for participants from parent trial DEN-315.

Time frame: 1 month post-booster dose at Month 43 (DEN-315)

Seropositivity Rate for Multiple (2, 3 or 4) Dengue Serotypes Post-booster Dose at 6 Months Post-Booster Dose by Serostatus at Baseline in the Parent Trials at Visit 5 (Month 48) (DEN-315)

Seropositivity rate for multiple Dengue serotypes, defined as the percentage of participants seropositive for more than one Dengue serotype, is derived from the titers of dengue-neutralizing antibodies. All 4 dengue serotypes (tetravalent), any 2 of the 4 dengue serotypes (bivalent), any 3 of the 4 dengue serotypes (trivalent). Seropositivity is defined as a reciprocal neutralizing titer ≥10. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial. The 4 dengue virus serotypes are DENV-1, DENV-2, DENV-3 and DENV-4. Reported here is the data from Visit 5 at Month 48 for participants from parent trial DEN-315.

Time frame: 6 months post-Booster dose at Month 48 (DEN-315)

Secondary Outcomes

Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes for All Participants Prior to the Booster Dose

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.

Time frame: Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Mont 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9

Geometric Mean Ratio (GMR) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials Prior to the Booster Dose

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared. Baseline seropositivity is defined as reciprocal neutralizing titer ≥10 for one or more dengue serotypes at baseline in the parent trial.

Time frame: Month 12 vs Month 0, Month 15 (DEN-304) vs parent trial Month 4, Month 42 (DEN315) vs parent trial Month 4, Month 0 vs parent trial Month 9, Month 12 vs parent trial Month 9

GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes in the Booster Phase

The geometric mean ratio is the geometric mean of the ratio of the two visits being compared.

Time frame: Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 6 vs post-booster M 1; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315)

GMR of Neutralizing Antibodies for Each of the 4 Dengue Serotypes by Serostatus at Baseline in the Parent Trials in the Booster Phase

Time frame: Months (M) 1&6 post-booster dose in current trial vs M 4 in parent trials; post-booster M 1 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs pre-booster (M 15 for DEN-304/M 42 for DEN-315); post-booster M 6 vs post-booster M 1

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) Within 7 Days Post-Booster Vaccination

Solicited local AEs at injection site are defined as pain, erythema and swelling that occurred within 7 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.

Time frame: Days 1 through 7 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Percentage of Participants With Solicited Systemic Adverse Events Within 14 Days Post-Booster Vaccination by Severity

Solicited systemic AEs are defined as fever, headache, asthenia, malaise and myalgia that occurred within 14 days post-booster dose at Month 15 (DEN-304) and Month 42 (DEN-315). AEs were graded by the investigator in the following manner: Mild: Grade 1: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities. Relieved with or without symptomatic treatment; Moderate: Grade 2: Sufficient discomfort is present to cause interference with normal activity. Only partially relieved with symptomatic treatment; Severe: Grade 3: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities. Not relieved with symptomatic treatment.

Time frame: Days 1 through 14 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Percentage of Participants With Any Unsolicited AEs in the Booster Phase

Time frame: Days 1 through 28 post-booster dose at Visit 3 (Month 15 [DEN-304]) and (Month 42 [DEN-315])

Percentage of Participants With Any Medically Attended AEs (MAAEs) in the Booster Phase

MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.

Time frame: Month 15 post-booster dose through Month 21 (DEN-304); Month 42 post-booster dose through Month 48 (DEN-315)

Percentage of Participants With Any Serious Adverse Events (SAEs) Prior to the Booster Dose

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine or placebo; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important event.

Time frame: Month 0 through Month 15 (DEN-304) and Month 42 (DEN-315)

Percentage of Participants With Any SAEs in the Booster Phase

Time frame: Month 15 post-booster dose after vaccination through Month 21 (DEN-304); Month 42 post-booster dose after vaccination through Month 48 (DEN-315)