Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) have been shown to be insufficient to protect against variants of concern (VOCs), while viral vector vaccines remain protective against the infection. Herein, we conducted a preliminary study to evaluate the safety and immunity in an adult population who received the conventional 2 dosage-regimen of inactivated SARS-CoV-2 vaccine; with an additional intradermal ChAdOx1 nCoV-19 reciprocal dosage (1:5). An Intramuscular ChAdOx1 nCoV-19 booster was also included as a control. Immediate and delayed local reactions were frequently observed in the fractional intradermal boost, but systemic side effects were significantly decreased compared to the conventional intramuscular boost. The anti-RBD-IgG levels, the neutralising function against delta variants, and T cell responses were significantly increased after boosting via both routes. Interestingly, the shorter interval elicited higher immunogenicity compared to the extended interval. Taken together, a reciprocal dosage of intradermal ChAdOx1 nCoV-19 booster reduces systemic adverse reactions and enhances non inferiority humoral and cellular immune responses compared to a full dose of intramuscular boosting. These findings provide for an effective vaccine management during the shortages of vaccine supply.

Evaluation of the safety and immunogenicity of fractional intradermal COVID-19 vaccines as a booster: A pilot study

“…Our findings of lower and milder systemic reaction are consistent with what was reported for intradermal injection of COVID-19 vaccines and other vaccines [9,16,17]. Intradermal administration may therefore increase vaccine uptake among those hesitant about vaccination due to high reactogenicity concern associated with the standard intramuscular injection of some COVID-19 vaccines.…”

“…However, we were not able to directly compare the T cell responses between those induced by intradermal injection and intramuscular injection. Previous studies of intradermal fractional ChAdOx1 booster in individuals who received CoronaVac primary series found similar T cell responses as standard intramuscular ChAdOx1 booster at two weeks post booster dose; these responses however were lower in intradermal injection than intramuscular injection at four weeks post booster dose [16,17]. For BNT162b2, the T cell responses was lower following intradermal fractional dose than the standard intramuscular dose at two weeks [18].…”

“…Our findings that robust immunogenicity is generated following an intradermal booster dose of ChAdOx1 given at 1/5 th of the standard dose in participants who previously received the standard intramuscular Coronavac is consistent with the findings from two other studies. These two studies found similar and non-inferior humoral and cellular immune responses between the standard intramuscular ChAdOx1 booster dose and the intradermal ChAdOx1 booster dose at 1/5 th of standard dosing [16,17]. For intradermal boosting using BNT162b2, our study findings were also consistent with a previous study that have reported significantly lower anti-RBD IgG concentrations and neutralizing antibodies against the delta variant when compared with corresponding intramuscular injection in individuals vaccinated with CoronaVac primary series [18].…”

Superior antibody and membrane protein-specific T cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

“…27,28 Several investigators recently compared fractional ID ChAdOx1/AZD-1222 with BNT162b2 boosters after 2 IM injections of CoronaVac, which induced similar antibody and T cell responses as IM boosters of the same respective vaccine. 29,30 However, ID usage of full doses of COVID-19 vaccines has not been studied thus far. Based on the collective available scientific data, we postulated that ID with the full dose of CoronaVac can induce greater immunogenicity against SARS-CoV-2 than the currently recommended IM.…”

The humoral and cellular immune response of a third dose adenoviral-based vectored vaccine after a single or 2 shots of inactivated COVID-19 vaccine in healthy adults

“…The majority of Thai people could only access the first Covid-19 vaccine, which was inactivated COVID-19 from China, called CoronaVac ® (Sinovac), in mid-2021 [5]. The adenoviral-based vectored vaccine (ChAdOx1 AZD1222) was available in Thailand a few months after the first arrival of CoronaVac [6]. Due to the limited vaccine supplies, The Ministry of Public health of Thailand implemented a heterologous prime-boost vaccination strategy to create herd immunity to combat the COVID-19 pandemic [7].…”