Single-dose CYD-TDV does not protect vs. dengue in both dengue-naïve and monotypic-profile children
13 Dec 2025
In a recent longitudinal, prospective, population-based cohort study done in Cebu, Philippines, a single dose of CYD-TDV did not immunize against RT-PCR-confirmed dengue in a healthy cohort of children who had, at most, one previous dengue virus (DENV) infection by serostatus at the outset of the study.
However, in cases with at least two previous bouts of dengue, the same dose did offer significant prevention from dengue hospitalization in the entire period of the study: three years from DENV serostatus baseline (70%, 95% CI 20–88; p=0·017) and follow-up (67%, CI 19–87; p=0·016). In contrast, the researchers noted that previous studies could not distinguish the efficacy of singe-dose CYD-TDV between children with one and two or more previous infections. [Lancet Infect Dis. 2024 Jul;24(7):737–745. doi: 10.1016/S1473-3099(24)00099-9]
From May 2 to June 2, 2017, the researchers, through rural health units, recruited 2,996 healthy 9-to-14 year-olds for profiling, baseline DENV serostatus-testing, and clinical surveillance in the Bogo and Balamban localities, prior to government-sponsored dengue vaccination. Participants who developed acute febrile illness were tested for dengue using RT-PCR. They then measured the relative risk of developing RT-PCR-diagnosed dengue in the children who obtained either one shot of CYD-TDV, or none, by baseline DENV serostatus.
Of note, Ylade et al. also observed the high incidence of RT-PCR-positive dengue extending up to the COVID-19 lockdown, which was seen as a spike in neutralizing antibody titers, from study baseline to follow-ups, but they qualified that the antibody responses were likely elicited from both CYD-TDV vaccine and DENV infection, proving the established observation that dengue can occur in children with multitypic profiles, although both dengue-naïve and monotypic profiles still had a higher incidence of infection in the study.
The importance of this study can be gleaned from the Department of Health’s recent experience with CYD-TDV vaccination. CYD-TDV is a triple-dose dengue vaccine indicated for ages nine and above, in endemic countries. Data from the initial implementation of the mass vaccination with CYD-TDV in 2016, Ylade et al. said, suggested that CYD-TDV be contraindicated in DENV-seronegative children, leading to the abrupt termination of the program and, thus, leaving children in Cebu administered with only one shot of the vaccine. Moreover, the study’s outcomes, along with the data from other studies, would be contrasted with the previous common belief that the vaccine offers protection in children with one previous infection, ie, monotypic, while multitypic profiles are said to be already immune from DENV in the first place
The researchers qualified that their findings on single-dose-vaccinated participants could not be used to change current guidelines on multi-dose vaccination against DENV. However, they said the findings do reinforce the importance of dosing compliance and of analyzing incomplete doses in future clinical trials.
However, in cases with at least two previous bouts of dengue, the same dose did offer significant prevention from dengue hospitalization in the entire period of the study: three years from DENV serostatus baseline (70%, 95% CI 20–88; p=0·017) and follow-up (67%, CI 19–87; p=0·016). In contrast, the researchers noted that previous studies could not distinguish the efficacy of singe-dose CYD-TDV between children with one and two or more previous infections. [Lancet Infect Dis. 2024 Jul;24(7):737–745. doi: 10.1016/S1473-3099(24)00099-9]
From May 2 to June 2, 2017, the researchers, through rural health units, recruited 2,996 healthy 9-to-14 year-olds for profiling, baseline DENV serostatus-testing, and clinical surveillance in the Bogo and Balamban localities, prior to government-sponsored dengue vaccination. Participants who developed acute febrile illness were tested for dengue using RT-PCR. They then measured the relative risk of developing RT-PCR-diagnosed dengue in the children who obtained either one shot of CYD-TDV, or none, by baseline DENV serostatus.
Of note, Ylade et al. also observed the high incidence of RT-PCR-positive dengue extending up to the COVID-19 lockdown, which was seen as a spike in neutralizing antibody titers, from study baseline to follow-ups, but they qualified that the antibody responses were likely elicited from both CYD-TDV vaccine and DENV infection, proving the established observation that dengue can occur in children with multitypic profiles, although both dengue-naïve and monotypic profiles still had a higher incidence of infection in the study.
The importance of this study can be gleaned from the Department of Health’s recent experience with CYD-TDV vaccination. CYD-TDV is a triple-dose dengue vaccine indicated for ages nine and above, in endemic countries. Data from the initial implementation of the mass vaccination with CYD-TDV in 2016, Ylade et al. said, suggested that CYD-TDV be contraindicated in DENV-seronegative children, leading to the abrupt termination of the program and, thus, leaving children in Cebu administered with only one shot of the vaccine. Moreover, the study’s outcomes, along with the data from other studies, would be contrasted with the previous common belief that the vaccine offers protection in children with one previous infection, ie, monotypic, while multitypic profiles are said to be already immune from DENV in the first place
The researchers qualified that their findings on single-dose-vaccinated participants could not be used to change current guidelines on multi-dose vaccination against DENV. However, they said the findings do reinforce the importance of dosing compliance and of analyzing incomplete doses in future clinical trials.