Comparison Of Equivalent Fractional Vaccine Doses Delivered By Intradermal And Intramuscular Or Subcutaneous Routes: A Systematic Review

Background: For certain vaccines, dosing can be reduced by intradermal (ID) immunization without loss of immunogenicity, as an alternative to standard routes of administration. However, a certain level of dose-sparing might also be achieved by reducing doses of intramuscular (IM) or subcutaneous (SC) vaccines. Method: We conducted a systematic review comparing identical reduced amounts of antigen delivered by either ID, or IM/SC routes (PROSPERO registration no. CRD42020151725). Results: Of 6015 articles identified, we included 26 articles, covering eight different vaccines. Equivalent immune responses were demonstrated in 19/26 studies, and 7/26 studies suggested inferior immune responses after IM/ SC immunization. Conclusions: We conclude that fractional dosed IM/SC vaccination is at best as immunogenic, but potentially inferior to ID vaccination. The safety profiles were at large comparable, although minor local adverse events were more common after ID delivery. Future vaccine trials, depending on the platform used, should add a fractional dose IM/SC arm, besides a fractional dose ID arm.