Seronegative Vaccinees May Not Benefit From Multiple Booster Doses of MMR Vaccine in Restoring Immunity

Despite the availability of a highly efficacious vaccine, a global resurgence of measles infections has occurred, largely due to decreased vaccination coverage and waning immunity following the two-dose vaccination schedule. This study aims to assess the cellular immune response in individuals who did not respond to the two-dose MMR vaccine and evaluate the efficacy and durability of immune responses after booster doses. An observational study was conducted involving 24 individuals who were seronegative for measles years after completing the two-dose MMR vaccine schedule. Of these, 11 seroconverted after a single booster dose, while 13 required an additional booster. Antibody levels were monitored 1 and 3 years post-booster. Cellular immune responses were evaluated in 10 nonresponders by in vitro stimulation of PBMCs with UV-inactivated measles virus. In nonresponders, measles virus stimulation did not induce significant alterations in T, B, or NK cell populations, indicating a lack of measles-specific immune memory. However, stimulation with rubella induced a significant immune response. Booster doses in subjects with waning antibodies resulted in low IgG titers, which significantly declined over 3 years. Neutralizing antibody titers were also low for both double and single booster recipients. This study highlights the limited long-term efficacy of booster doses in individuals with waning immunity or nonresponsiveness to the measles vaccine. Current vaccination strategies relying on booster doses may not be sufficient for sustained protection in these individuals. Improving vaccine formulations to elicit stronger and longer-lasting immunity is essential for effective measles control and elimination.