Background: The SARS-CoV-2 (COVID-19) pandemic has widely spread with numerous waves of different variants of concern, which resulted in shortage of COVID-19 vaccine. Fractional intradermal (ID) dosing regimens for COVID-19 vaccination could be considered as an alternative to minimize possible adverse effects and ease up vaccine supply. Methods: This randomized, open-label study was conducted at a single center, Siriraj Hospital, Bangkok, Thailand. This study was conducted in two sub-studies. The first study was to determine the safety and immunological response of fractional ID as a booster dose. The following study focused on the accelerated fractional ID as primary series. The first study was conducted among 150 volunteers who completed 2-dose IM primary series between 12 and 24 weeks earlier. Those participants who received the primary series of ChAdOx1 (IM) were allocated to vaccinated 0.05 mL BNT162b2 (ID) as booster, while participants previously vaccinated with primary series of BBIBP-CorV (IM) or CoronaVac (IM) were randomized to receive fraction doses of 0.1 mL ChAdOx1 (ID) or 0.05 mL BNT162b2 (ID). The second study was carried out among 90 volunteers who were naïve to SARS-CoV-2 infection. The two vaccinations, 2 injections for each vaccination on a separate arm at the deltoid area, given in an accelerated schedule of 7 days apart. In the initial part of this study, 50 participants were randomly assigned to 5 groups equally consisting of homologous primed ChAdOx1 and BNT162b2, and homologous primed between CoronaVac – ChAdOx1, CoronaVac – BNT162b2 and ChAdOx1 – BNT162b2. Additional participants were recruited in the two groups (20 per group) with the highest proportion of adverse events. The participants were observed for at least 30 min following the vaccination for any immediate adverse events, and self-reported adverse events were collected for 7 using an electronic diary in Google Form. The immunogenicity was determined by the level of anti-receptor binding domain (anti-RBD IgG) of the SARS-CoV-2 and neutralizing antibody (NT) against various variants. T-cell responses were measured by ELISpot using S-peptide and NMO-peptide stimulation. Results: In the first study among volunteers who completed the primary series, 105 eligible participants were randomly assigned to 3 study groups equally (n=35, 33.33% per group). The overall median age was 38 years, around half of participants were male, and the BMI was normal. There were no significantly different in baseline demographic characters. At 2 weeks following booster dose, participants who received 2-dose primary series of BBIBP-CorV (IM) or CoronaVac (IM) followed by BNT162b2 (ID) as booster induced the highest antibody IgG (GMC=1,723.00 BAU/mL). ID administration induced lower IgG than the reference IM of the same vaccine. Likewise, NT levels following ID route were generally lower than that following reference IM, except for the group that received ChAdOx1 (ID) boost which induce NT against Omicron in the similar level to that of the reference IM. Adverse events (AEs) were mostly mild to moderate levels of severity in all study groups. 28.57% of the injection site reaction and 64.74% of systemic AEs were reported. For the second study, 57 eligible participants were randomly assigned to receive 5 study groups of fractional accelerated ID as primary series. The overall median age was 35 years (IQR=28-45 years). At 2 weeks following the primary series, participants who received 2-dose (ID) of ChAdOx1 - BNT162b2 have induced the significantly highest antibody IgG (GMC=597.29 BAU/mL), followed by BNT162b2 - BNT162b2 (GMC=414.84 BAU/mL). Overall, ID have shown a significantly lower antibody IgG than reference IM of the same vaccine regimens (p<0.001). The regimen ChAdOx1 - BNT162b2 also induced the highest NT levels against Wuhan (GM=254.20) and Omicron BA.1 (GM49.34). All groups had similarly low NT against Omicron to the references IM (p=0.304). Likewise, the ELISpot-S response was highest in the group ChAdOx1-BNT162b2 (GM=441.34 SFU/106 cells). There was no significant difference in the proportion of AEs between the study group in this study. Conclusions: The fractional ID as a booster dose has generated antibody responses against SARSCoV-2 infection but in a lower level than IM references; however, well tolerated. It should not be the primary route of vaccination but may be considered in cases of vaccine shortage. Likewise, accelerated fractional ID dosing regimens as primary series is immunogenic for both humoral and cellular but with lower antibody levels than IM references. The accelerated ChAdOx1-BNT162b2 induced the highest immunogenicity and may be considered in the next pandemic that require rapid priming particularly when the vaccine supply is insufficient.