Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore

Yee Sin Leo, Anneliese Wilder-Smith, Sophia Archuleta, Lynette P Shek, Chia-Yin Chong, Hoe Nam Leong, Chian Yong Low, May-Lin Helen Oh, Alain Bouckenooghe, T Anh Wartel, Denis Crevat, Yee Sin Leo, Anneliese Wilder-Smith, Sophia Archuleta, Lynette P Shek, Chia-Yin Chong, Hoe Nam Leong, Chian Yong Low, May-Lin Helen Oh, Alain Bouckenooghe, T Anh Wartel, Denis Crevat

Abstract

This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated viruses (CYD-TDV) and the dengue virus serotype-specific antibody responses before and 28 d after each vaccination. Participants were randomized 3:1 to receive three doses of CYD-TDV or a control vaccine at 0, 6 and 12 mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed hepatitis-A for children (aged 2-11 y) or influenza vaccine for adolescents (12-17 y) and adults (18-45 y). Between April and October 2009, 317 children, 187 adolescents and 696 adults were enrolled. In all age groups, reactogenicity was higher after the first injection of CYD-TDV than after placebo control. Reactogenicity after subsequent CYD-TDV doses was no higher than after the first dose, and tended to be lower or similar to that seen after active control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses. Post-dose 3, 66.5% of all participants were seropositive to all four serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from 43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher in children than in adolescents. These results support the continued development of CYD-TDV for the prevention of dengue disease.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3579907/bin/hvi-8-1259-g1.jpg
Figure 1. Progress of participants through the study: summary of dispositions and discontinuations.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3579907/bin/hvi-8-1259-g2.jpg
Figure 2. Age-specific reactogenicity of CYD-TDV: proportion of participants by age and vaccine group with different categories of adverse events after each vaccination. Control group participants aged < 12 y at inclusion received intramuscular doses of hepatitis A vaccine and those aged ≥ 12 y received subcutaneous inactivated influenza vaccine.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3579907/bin/hvi-8-1259-g3.jpg
Figure 3. Seropositivity rates (percentage of participants PRNT50 titer ≥ 10 1/dil) against each of the four dengue virus serotypes (1, 2, 3 and 4) at baseline and 28 d after the third vaccination in all participants and in each of the three age groups.

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Source: PubMed

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