Coadministration of dengue plus Tdap vaccines feasible, safe in seropositive patients

Concomitant or sequential administration of the combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine and the tetravalent dengue vaccine (CYD-TDV; sold under the brand name Dengvaxia) produces similar immunogenicity and safety profiles in baseline dengue seropositive participants, a Philippines study has shown.

“The coadministration of CYD-TDV with Tdap in participants who were baseline dengue seropositive elicited a noninferior immune response compared with sequential administration, with a consistent safety profile,” the researchers said. “The study results demonstrate the feasibility of coadministration of CYD-TDV and Tdap vaccine.”

This phase IIIb, randomized, open-label, multicentre study in the Philippines included 688 individuals aged 9 to ≤60 years who received three doses of CYD-TDV 6 months apart, with the first dose administered either concomitantly or sequentially (28 days post-Tdap).

The researchers measured antibody levels against pertussis antigens (PT, FHA, PRN, FIM) and tetanus toxoid at baseline and 28 days after first doses of Tdap vaccine and CYD-TDY using enzyme-linked immunosorbent assay, micrometabolic inhibition test-toxin neutralization assay, and plaque reduction neutralization test. Immunogenicity and safety were evaluated in all participants.

Of the participants, 629 (91.4 percent) were baseline dengue seropositive (concomitant group: n=314; sequential group: n=315). Concomitant administration showed a noninferior immune response compared with sequential vaccination after the first dose. [Pediatr Infect Dis J 2021;40:856-863]

Moreover, between-group geometric mean antibody concentration ratios for anti-PT, anti-PHA, anti- PRN, and anti-FIM were close to 1; between-group differences in percent achieving seroprotection (titres ≥0.1 IU/mL) were 0.26 percent (diphtheria), and 0.66 percent (tetanus); and between-group geometric mean antibody titre ratios for dengue serotypes 1–4 were close to 1. 

Both treatment groups showed similar safety profiles. Pain after injection was the most common reaction, followed by headache and malaise. Immediate unsolicited systemic AEs or adverse reactions were not reported, and no early terminations due to a serious AE occurred.

Of note, seroprotection rates of antibodies against diphtheria and tetanus toxoids (close to 90 percent for both groups) were lower than the expected >99-percent seroprotection used for sample size calculations.

“A possible explanation for the lower seroprotection is the inclusion of older adults, who have been shown to have lower rates,” the researchers said. “As results were not assessed by age group in this study, we cannot confirm if seroprotection declines with age.” [Clin Exp Immunol 2017;187:93-99; J Korean Med Sci 2019;34:e31; Vaccine 2015;33:2594-2601]

The current findings support those from previous studies, indicating that vaccines, such as meningococcal and human papillomavirus, can be safely and effectively coadministered with other vaccines in adolescents and adults to improve vaccination rates and reduce the burden of vaccinations. [Hum Vaccin Immunother 2019;15:2205-2216; Vaccine 2020;38:119-134]

“The sudden increase in incidence and mortality rates of dengue worldwide in 2019, with the declaration of an epidemic in the Philippines during the same year, highlights the need for an effective vaccine,” the researchers said. [https://www.doh.gov.ph/press-release/DOH-DECLARES-NATIONAL-DENGUE-EPIDEMIC]

“Diphtheria, pertussis, and tetanus vaccination is part of an ongoing national vaccination program in the Philippines Expanded Program on Immunization with an estimated vaccination coverage of 65 percent in 2019,” they added. [https://www.doh.gov.ph/expanded-program-on-immunization; https://www.who.int/immunization/monitoring_surveillance/data/phl.pdf]

The current study was limited by its termination prior to the third CYD-TDV dose and the inability to test the noninferiority of this dose.