Immunogenicity and Reactogenicity of Messenger RNA Coronavirus Disease 2019 Vaccine Booster Administered by Intradermal or Intramuscular Route in Thai Older Adults

Abstract Background Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. Methods Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12–24 weeks earlier were randomized to receive a booster vaccination by either ID (20 µg mRNA-1273 or 10 µg BNT162b2) or intramuscular (IM) (100 µg mRNA-1273 or 30 µg BNT162b2) route. Anti–receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibody (NAb), and interferon gamma (IFN-γ)–producing cells were measured at 2–4 weeks following vaccination. Results Of 210 participants enrolled, 70.5% were female and median age was 77.5 (interquartile range, 71–84) years. Following booster dose, both ID vaccinations induced 37% lower levels of anti-RBD IgG compared with IM vaccination of the same vaccine. NAb titers against ancestral and Omicron BA.1 were highest following IM mRNA-1273 (geometric mean, 1718 and 617), followed by ID mRNA-1273 (1212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN-γ responses were similar or higher in the ID groups compared with IM groups. ID route tended to have fewer systemic adverse events (AEs), although more local AEs were reported in the ID mRNA-1273 group. Conclusions Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative for older people. Clinical Trials Registration TCTR20220112002. In this randomized controlled trial in elderly, fractional intradermal COVID-19 booster vaccination with BNT162b2 or mRNA-1273 induced lower antibody but similar cellular immune response compared with standard intramuscular vaccination. Intradermal route induced relatively fewer systemic but more local adverse events.