Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study

Abstract

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

Keywords: COVID-19 vaccination; Thailand; booster; heterologous; intradermal.

Figure 1

Consort Diagram showing enrollment of each group in initial phase and extended phase. Group 1 and 2 received two doses of CoronaVac intramuscularly (CoronaVac-prime), Group 3 and 4 received two doses of ChAdOx1 intramuscularly (ChAdOx1-prime), and Group 5 and 6 received two doses of BNT162b2 intramuscularly (BNT162b2-prime). Each group was randomized to receive intradermal BNT162b2 (0.05 mL, 1/6th of standard dosage) or ChAdOx1 (0.1 mL, 1/5th of standard dosage). Additional participants were enrolled in the extended phase to join Groups 1, 2, and 3.

Figure 2

Geometric mean concentration of anti-RBD IgG pre- and post-intradermal (ID) booster dose in the initial phase (A) and in initial and extended phase (B). Intramuscular (IM) boosting of the same vaccine regimens from the previous study [19] is included as a reference group. Error bars represent geometric mean concentration, plus 95% confidence intervals. BAU: binding antibody units.

Figure 3

Neutralizing antibody titers of live virus plaque reduction neutralization assays (PRNT₅₀) against delta strain (A) and omicron strains (B) following intradermal (ID) booster. Intramuscular (IM) boosting of the similar vaccine regimens from the previous study [19] is included as the reference group. Error bars represent geometric mean titers plus 95% confidence intervals.

Figure 4

SARS-CoV-2 antigen-specific T-cell response by ELISPOT after intradermal (ID) booster. (A) Spike-specific T cell responses. (B) Nucleocapsid-membrane-open reading frame-T cell responses. Error bars represent geometric mean concentrations plus 95% confidence intervals. SFU: spot-forming units.

Figure 5

Self-reported adverse events following intradermal boosting consist of local injection site reaction (A) and systemic reaction (B). Intramuscular boosting of the similar vaccine regimens from the previous study [19] is included as a reference group.