Abstract
Importance: Intradermal administration of SAR-COV-2 vaccines may be the alternative route for vaccination in resource-limited settings. By given lower amount of exposed antigen, the one-fifth of regular dose via intradermal administration (ID) had shown similar immunogenicity and less systemic adverse reaction comparing to intramuscular administration (IM). Objectives : To determine adverse events (AEs) and immunogenicity of intradermal administration of primary series and booster dose of CoronaVac, ChAdOx1 and BNT162b2 in healthy population. Design: This prospective study was conducted from September 2021 to February 2022. Setting: A single center, university-based tertiary care center in Bangkok. Participants: A total of 140 healthy volunteers were 80 SARS-Cov-2 vaccine-naïve and 60 volunteers who completed primary series of IM CoronaVac, ChAdOx1 or BNT162b2. Exposure: In vaccine naïve volunteers, they were divided into 5 groups to receive following regimens (4 weeks apart): 1) ID CoronaVac 0.1 ml and ID ChAdOx1 0.1 ml (n=20); 2) ID ChAdOx1 0.1 ml and ID ChAdOx1 0.1 ml(n=20); 3) ID BNT162b2 0.05 ml and ID BNT162b2 0.05 ml(n=20); 4) IM ChAdOx1 0.5 ml and ID ChAdOx1 0.1 ml(n=10); 5) IM BNT162b2 0.3 ml and ID BNT162b2 0.05 ml (n=10). In volunteers who completed primary series, they were given ID ChAdOx1 0.1 ml or ID BNT162b2 0.05 ml as a booter. Main Outcomes and Measures: Self-reported AEs were collected for 7 days following each vaccination using electronic diary. The immunogenicity was determined by the level of IgG antibodies against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit). The plaque reduction neutralization tests (PRNT) and Focus Reduction Neutralization Tests (FRNT) against original (Wuhan) and circulating VOCs were performed in subset of random samples at 2 weeks after the second dose or booster dose. The T-cell response was measured using ELISPOT. Participants who had positive anti-np or anti-RBD-IgG at baseline were excluded from analysis.
Results: Among 67 vaccine-naïve participants, the median (interquartile range: IQR) age was 34.5 (24.5-44) years old and 48.75% were female. Participants who received the ID administration reported less systemic reaction (58%) than the IM administration (80%). Immunogenic response following IM BNT162b2-ID BNT162b2 provided the highest IgG level with geometric means of 13,427 AU/mL and GMT 23.05 against omicron strain followed by ID BNT162b2-ID BNT162b2, ID CoronaVac-ID ChAdOx1, IM ChAdOx1-ID ChAdOx1, and ID ChAdOx1- ID ChAdOx1. A total of 58 participants were enrolled and received third dose booster. Their median age was 43 years old (IQR 35-48) and 67.24% were female. The geometric mean ratios (GRM) (post boosted/pre boosted) of ID BNT162b2 and ID ChAdOx1 following CoronaVac primary series were 33.83 and 24.89, respectively. GMRs of ID BNT162b2 and ID ChAdOx1 were 7.90 and 1.29 following primary series of ChAdOx1 and were 2.40 and 0.97 following primary series of BNT162b2. The third dose ID booster of BNT162b2 provided higher GMT against omicron and delta variants following primary series of ChAdOx1 and BNT162b2; however, ID ChAdOx1 showed higher GMT against delta and omicron following primary series of CoronaVac. Conclusions: Intradermal administration of SAR-COV-2 vaccines show less systemic adverse reaction and can increase both humoral and cellular immunogenicity. Immunogenic response following ID BNT162b2 in both vaccine-naïve participants and for booster dose are better than ID CoronaVac and ID ChAdOx1.
