Dengvaxia booster can restore antibody titres years after initial doses
A booster injection of CYD-TDV (Dengvaxia) can generally restore antidengue antibody titres 5 years after a three-dose schedule, according to a new Singapore study.
“This study was designed to demonstrate the noninferiority, in terms of antidengue antibody geometric mean titres ratios (GMTRs) of a CYD-TDV booster … in Singapore,” said researchers. “Noninferiority of the CYD-TDV booster dose was demonstrated for serotypes 1, 3 and 4, but not for serotype 2.”
Seventy-five participants received the booster, while 28 were given placebo. CYD-TDV increased GMTs over 28 days for all dengue serotypes. For example, from a baseline value of 13.5, GMT for serotype 1 increased to 37.7 by day 28. For serotype 2, GMTs rose from 18.4 to 56.2. [Hum Vaccin Immunother 2019;doi:10.1080/21645515.2019.1661204]
Similarly, GMTs increased from 22.4 to 105 and from 28 to 123 for serotypes 3 and 4, respectively, over the 28-day observation period. No such changes were reported for those who received placebo.
Using paired t-tests to reject four individual null hypotheses, the researchers further established the noninferiority of CTD-TDV compared with the third vaccine dose, but only for serotypes 1 (GMTR, 1.34, 95 percent CI, 0.998–1.79), 3 (GMTR, 0.979, 0.746–1.28) and 4 (GMTR, 1.27, 0.918–1.75). This effect did not exist for dengue serotype 2 (GMTR, 0.603, 0.439–0.829).
Noninferiority was established as long as the lower-bound of the CIs did not drop below 0.5, the researchers said.
“Nonetheless, the GMTs for serotype 2 increased by more than twofold from pre- to postbooster with CYD-TDV. In addition, analysis of covariance, adjusting for the prebooster titres, confirmed that CYD-TDV booster increased neutralizing antibody levels for each serotype,” they added.
In terms of seropositivity, the booster had similar effects. Compared to prebooster levels, administration of CYD-TDV increased the rate of seropositivity to at least 1 (93.3 percent to 100 percent), 2 (52.0 percent to 96.0 percent), 3 (33.3 percent to 85.3 percent) and all (24.0 percent to 68.0 percent) serotypes after 28 days. In comparison, the corresponding rates in the placebo group tended to remain stagnant.
CYD-TDV had a good safety profile overall, such that there was only one case of serious adverse event in the booster group, but this was deemed unrelated to the treatment. There were no deaths, no adverse events leading to discontinuation and no cases of dengue.
“In summary, this study indicates that antidengue antibody titres can generally be restored with a booster injection to levels similar to those initially observed after the three-dose schedule in a population in a low dengue endemicity area,” said the researchers.
“There were no new safety issues with the CYD-TDV booster in this study, and the vaccine was well tolerated. Most of the local and systemic reactions were of mild intensity and of short duration,” they added. “The proportion of participants who reported at least one solicited adverse reaction following the CYD-TDV booster tended to be lower than those after any CYD-TDV injection in the original CYD28 study.”