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BackgroundCurrently, booster dose is needed after 2 doses of inactivated COVID-19 vaccine. With limited resource and shortage of COVID-19 vaccine, intradermal(ID) administration might be a potential dose-sparing strategy. ObjectiveTo determine antibody response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine(AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult. MethodsThis is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1x1010 viral particles,0.1ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against wild type and delta variant and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14 or 28, and day90 post booster. Solicited reactogenicity was collected during 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain [≥]80%inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route. ResultsFrom August2021, 100 adults with median(IQR) age of 46(41-52) years participated. At baseline, geometric means(GMs) of sVNT against delta strain prior to booster were 22.4%inhibition(95%CI 18.7-26.9) and of anti-S-RBD IgG were 109.3(95.4-125.1)BAU/ml. GMs of sVNT against delta strain were 92.9%inhibition(95%CI 87.7-98.3) at day14 and 73.1%inhibition(66.7-80.2) at day90 post ID booster. The differences of proportion of participants with sVNT to delta strain[≥]80%inhibition in ID recipients versus IM were +4.2%(95%CI-2.0to10.5) at day14, and -37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1(95%CI1770.9-2343.2) at day14 and 744.6(650.1-852.9) BAU/ml at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM(p=0.003). Only 18% reported feverish, compared with 37% of IM(p=0.003). Common reactogenicity was erythema(55%) at injection site while 7% reported blister. ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity. HighlightsO_LIIntradermal AZD1222 booster vaccine gave comparable short-term immunogenicity but lower 90-day immunogenicity with conventional intramuscular vaccine. C_LIO_LILower systemic but higher local reactogenicity was found in intradermal AZD1222 booster vaccine. C_LIO_LIBlister and pruritus could be seen after intradermal AZD1222 booster vaccine. C_LI