Discussion
infection
INFECTION, RABIES
This pilot study explored the immunogenicity and reactogenicity of accelerated schedules of fractional, homologous or heterologous, ID COVID-19 immunization. Accelerated two-dose ID regimens, administered 7 days apart, as fractions of 17% (for BNT162b2) and 20% (for CoronaVac and ChAdOx1) of their standard IM dosages were immunogenic against the ancestral strain. Homologous regimens of BNT162b2-BNT162b2 and heterologous ChAdOx1-BNT162b2 induced higher humoral and cellular immune responses against the ancestral Wuhan strain than homologous ChAdOx1-ChAdOx1 and CoronaVac-ChAdOx1. However, they induced lower antibody responses than their respective conventional IM dosing (two doses, 4 weeks apart). Heterologous regimens also induced higher measurable neutralizing antibody titers than their homologous regimens. However, fractional ID dosing regimens induced poor neutralizing antibody responses against omicron subvariants, comparable to two-dose IM regimens.Vaccine administration Accelerated schedules provide rapid vaccine-induced immunity and have been widely used in post-exposure prophylaxis against rabies. The WHO recommends an accelerated schedule on days 0, 3, 7, and 14-28 to rapidly achieve the immune induction required to prevent rabies infection (Low or negligible antibody responses against omicron subvariants were observed. This was consistent with earlier findings in primary series administered as two doses IM, where boosters were required to generate robust cross immunity against omicron due to its immune evasion properties (Additionally, as observed in other studies, homologous and heterologous fractional ID regimens were well-tolerated, with low incidences of systemic AEs and no severe local reactions (Our study has some limitations. First, this is a pilot study and our sample size is small. However, we could still observe significant differences between the four vaccine groups with reference to their IM regimens. Second, we were not able to compare our data with an IM primary series within the same cohort. We minimized the variability of our findings somewhat by using reference data from the same setting, and testing methods as the previous cohort. Third, we did not have a reference IM group for ELISpot analysis. Therefore, we were unable to compare cellular immune responses between IM and ID administration directly. Fourth, there are no accelerated IM schedules with similar vaccination regimens 7 days apart for comparison. Lastly, our data may not be generalizable to other populations (To conclude, we found that accelerated fractional COVID-19 vaccines administered ID are immunogenic against the ancestral strain but insufficient for omicron subvariants. Our regimens were able to prime immunity, as demonstrated by humoral and cellular immune responses. With the appropriate vaccine, such strategies may be useful for containing future outbreaks, particularly in cases of vaccine shortages. Further studies on accelerated schedules warrants research on booster dose responses.