Humoral and cellular immunogenicity and safety following a booster dose of a tetravalent dengue vaccine 5+ years after completion of the primary series in Singapore: 2-year follow-up of a randomized phase II, placebo-controlled trial
Open Access
- 24 February 2021
- journal article
- research article
- Published by Informa UK Limited in Human Vaccines & Immunotherapeutics
- Vol. 17 (7), 2107-2116
- https://doi.org/10.1080/21645515.2020.1861875
Abstract
The tetravalent dengue vaccine (CYD-TDV) is approved for use as a 3-dose series for the prevention of dengue in seropositive individuals ≥9 years. A randomized, placebo-controlled, phase II study of a booster dose of CYD-TDV in individuals who completed the 3-dose schedule >5 years previously (NCT02824198), demonstrated that a booster restored neutralizing antibody titers to post-dose 3 levels. We present additional immunogenicity assessments up to 24 months post-booster, and B- and T-cell responses in a participant subset. Participants aged 9–45 years that had received all three doses of CYD-TDV were randomized 3:1 to receive a booster dose of CYD-TDV (n = 89) or placebo (n = 29). Neutralizing antibody levels at Months 1, 6, 12, and 24 post-booster were assessed by plaque reduction neutralization test. In a subset, B-cell responses were assessed by a fluorescent immunospot assay, and T-cells analyzed by flow cytometry at Days 0, 7, 12, Months 1 and 12. We observed an increase of antibody titers Month 1 post-booster, then a gradual decline to Month 24. In the CYD-TDV booster group, an increase in plasmablasts was seen at Day 7 declining by Day 14, an increase in memory B-cells was observed at Day 28 with no persistence at Month 12. CYD-TDV booster recalled a CD8+ T-cell response, dominated by IFN-γ secretion, which decreased 12 months post-booster. This study showed a short-term increase in antibody titers and then gradual decrease following CYD-TDV booster injection >5 years after primary immunization, and the presence of memory B-cells activated following the booster, but with low persistence.Keywords
Funding Information
- Sanofi Pasteur
This publication has 22 references indexed in Scilit:
- Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccinationHuman Vaccines & Immunotherapeutics, 2017
- Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune ProtectionPLOS ONE, 2015
- Immunogenicity and safety of a tetravalent dengue vaccine during a five-year follow-up periodTrials in Vaccinology, 2015
- Assessment of bivalent and tetravalent dengue vaccine formulations in flavivirus-naïve adults in MexicoHuman Vaccines & Immunotherapeutics, 2014
- Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in SingaporeHuman Vaccines & Immunotherapeutics, 2013
- Optimization and Validation of a Plaque Reduction Neutralization Test for the Detection of Neutralizing Antibodies to Four Serotypes of Dengue Virus Used in Support of Dengue Vaccine DevelopmentThe American Journal of Tropical Medicine and Hygiene, 2013
- Origin and Function of Circulating Plasmablasts during Acute Viral InfectionsFrontiers in Immunology, 2012
- B-cell responses to vaccination at the extremes of ageNature Reviews Immunology, 2009
- Cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjectsVaccine, 2008
- CD8+ T cell efficacy in vaccination and diseaseNature Medicine, 2008