Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

Abstract

Background: Currently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy.

Objective: To determine immunologic 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.

Methods: This 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(1×10¹⁰ viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 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.

Results: From August2021, 100 adults with median age of 46 years(IQR 41-52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7-26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4-125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2-96.8) at day14, 73.1% inhibition (66.7-80.2) at day90, and 22.7% inhibition (14.9-34.6) at day180. The differences of proportion of participants achieving sVNT against 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 BAU/ml (95%CI 1770.9-2343.2) at day14 and 744.6 BAU/ml(650.1-852.9) 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). Common reactogenicity was erythema at injection site(53%) while 7% reported blister.

Conclusion: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.

Keywords: AZD1222; Anti-SARS-CoV-2 IgG; Booster dose; ChAdOx1 nCoV-19 vaccine; CoronaVac vaccine; Intradermal; Neutralizing antibody titer; SARS-CoV-2 vaccine.

Fig. 1

Flow diagram of study participants. CMI: Cell-mediated immunity, ID: Intradermal, IM: Intramuscular, ^†IM group from standard-dose AZD1222 booster in healthy adult completing 2-dose CoronaVac at the same study site (Chulalongkorn University, Bangkok, Thailand) of Nanthapisal S, et al. A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines. Vaccine 2022. https://doi.org/10.1016/j.vaccine.2022.03.036.

Fig. 2

Solicited reactogenicity within 7 days of ID and IM^† AZD1222 booster after 2-dose CoronaVac in healthy adult. ID: Intradermal, IM: Intramuscular, ^†IM group from standard-dose AZD1222 booster in healthy adult completing 2-dose CoronaVac at the same study site (Chulalongkorn University, Bangkok, Thailand) of Nanthapisal S, et al. A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines. Vaccine 2022. https://doi.org/10.1016/j.vaccine.2022.03.036.

Fig. 3

Geometric means (95% CI) of sVNT against delta strain (% inhibition) at day 0, 14, 28, and 90 of ID and IM^† AZD1222 booster after 2-dose CoronaVac in healthy adult. P-value was evaluated by two sample independent t test. ID: Intradermal, IM: Intramuscular, sVNT: Surrogate virus neutralization test ^†IM group from standard-dose AZD1222 booster in healthy adult completing 2-dose CoronaVac at the same study site (Chulalongkorn University, Bangkok, Thailand) of Nanthapisal S, et al. A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines. Vaccine 2022. https://doi.org/10.1016/j.vaccine.2022.03.036.

Fig. 4

ELISpot assay at day 0, day 28, and day 90 of ID and IM^† AZD1222 booster in healthy adult completing 2-dose CoronaVac: (A) Interferon-γ ELISpot response to SNMO overlapping peptides of SARS-CoV-2, (B) RBD-specific IgG ELISpot assay. Comparison of results between day 0 and day 28 or day 90 within ID or IM group was evaluated by Wilcoxon signed rank test. Comparison of results between ID and IM group was evaluated by Wilcoxon rank sum test, yielding no statistical difference at all time points. ID: Intradermal, IM: Intramuscular, RBD: Receptor binding domain, SFU: Spot forming unit, SNMO: Spike (S) nucleoprotein (N), membrane protein (M), and open reading frame proteins (O) of SARS-CoV-2 ^†IM group from standard-dose AZD1222 booster in healthy adult completing 2-dose CoronaVac at the same study site (Chulalongkorn University, Bangkok, Thailand) of Nanthapisal S, et al. A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines. Vaccine 2022. https://doi.org/10.1016/j.vaccine.2022.03.036.