Priming effect of previous Japanese encephalitis vaccination on humoral immune response to tetravalent dengue vaccine

Abstract

The potential priming effect of prior Japanese encephalitis vaccination (JEV) on antibody responses to tetravalent live-attenuated chimeric dengue virus vaccine (TDV) was assessed. The TDV vaccine viruses were constructed by replacing genes for non-structural pre-membrane (PrM) and envelope (E) proteins of the attenuated YF 17D vaccine with wild-type dengue serotypes sequences. In a randomized, controlled, multicenter, Phase II study in Mexico City, 18-45 year-old participants received two injections of TDV at days 0 and 105 (Group 1) or 3 injections of JE-VAX at days -14, -7, and 0 followed by one dose of TDV at day 105 (Group 2). Dengue antibody levels were determined by microneutralization assay before, 28 and 60 days after each TDV vaccination and at day 365. Viremia was assessed by PCR methods 7-14 and 21 days after each TDV vaccination. Safety was documented after vaccination through day 28. Seropositivity rates (antibody level >10 1/dil) 28 days after 2 doses of TDV (Group 1, n=31) were 61%, 36%, 71% and 75% respectively against dengue serotypes 1-4. After 1 dose of TDV among JEV primed (Group 2, n=30), these rates were 85.2%, 85.2%, 85.2%, 92.6%. GMTs against dengue serotypes 1-4 for Group 1 / Group 2 were: 18.4/37.4, 12.6/27.4, 16.7/42.4, and 56.5/219. The percentage of seropositive subjects for at least 3 serotypes was 46% for Group 1 and 78% for Group 2. JEV priming did not increase viremia, which remained low and infrequent in both groups. Serotype 4 was the most frequently detected followed by serotype 3. Both groups had acceptable and similar safety profiles. Injection site pain and headache were the most common solicited reactions. In conclusion, seropositivity rates and GMTs of subjects primed with JEV vaccine receiving 1 dose of TDV were higher than those who received 2 doses of TDV, suggesting that pre-existing JE immunity may boost antibody responses to the TDV without modifying the safety profile.