Accelerated Dengue/Yellow Fever Vaccine Schedule Noninferior to Conventional Schedule

vaccine, syringe close up
Study data demonstrates an early benefit to receiving Japanese Encephalitis vaccination prior to CYD-TDV in terms of higher overall anti-dengue virus neutralizing titers, although this benefit appears to wane after several months.

Providing an accelerated dosing schedule of the chimeric yellow fever-derived tetravalent dengue vaccine (CYD-TDV) has not demonstrated a significant difference in neutralizing antibody levels compared with the currently approved schedule. Administrating the Japanese encephalitis vaccine before CYD-TDV may provide a benefit in terms of antibody levels and activated CD8+ T cells, according to a study published in The Journal of Infectious Diseases.

This phase 2, randomized, open-label trial included 90 participants with a mean age of 29.5±6.5 years, 50 of whom completed the study. The study was conducted at the State University of New York Upstate Medical University, and had a primary endpoint of immunogenicity of 4 distinct regimens of CYD-TDV (assessed by a 50% reduction neutralization titration in dengue serotype plaque at baseline, 28 days after each CYD-TDV dose, and 6 months after the third CYD-TDV dose). Safety metrics were also assessed.

Participants were divided into groups as follows: group 1 received an accelerated CYD-TDV schedule (age 0, 2, and 6 months), group 2 received the currently accepted CYD-TDV schedule (age 0, 6, and 12 months), group 3 received an accelerated CYD-TDV schedule as well as 2 doses of Japanese encephalitis vaccine at month 0, and group 4 received 2 Japanese encephalitis doses (age 0 and 1 month) and an accelerated CYD-TDV schedule.

Neutralizing antibody production was similar across all treatment groups regardless of accelerated vs conventional dosing schedule. No difference in neutralizing antibody titers was observed between those receiving concurrent Japanese encephalitis vaccination and those receiving only CYD-TDV. Immunophenotyping revealed a significant increase in CD8+ T cell activation 2 weeks after the initial administration of CYD-TDV. The greatest CD8+ activation was observed after this initial dose, though some participants also displayed a significant increase after later doses. These results showed a satisfactory safety profile for CYD-TDV.

This study was limited by reliance on measurements of neutralizing antibodies and the possibility that these are not the most accurate marker for infection prevention, as well as a high number of participants who did not complete the study. 

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The study authors concluded that “no significant differences in neutralizing antibody titers were observed” among those given an accelerated schedule compared with those on the currently approved schedule. Furthermore, the study researchers found evidence suggesting that “concomitant [Japanese encephalitis] vaccine administration alters the early innate response to the CYD-TDV vaccine, ultimately impacting the T cell response.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Glass A, Polhemus M, Wang D, et al. The effects of Japanese encephalitis vaccine and accelerated dosing scheduling on the immunogenicity of the chimeric yellow fever derived tetravalent Dengue vaccine (CYD-TDV): a phase II, randomized, open-label, single center trial in adults aged 18 to 45 years in the United States [published online November 22, 2019]. J Infect Dis. doi: 10.1093/infdis/jiz592