Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population

Abstract

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

Safety and Immunogenicity of the Third Booster Dose with Inactivated, Viral Vector, and mRNA COVID-19 Vaccines in Fully Immunized Healthy Adults with Inactivated Vaccine

“…Our cohort study of AZD1222 booster was also similar to that previously reported in a real-world study [13]. Additionally, the antibody response after a booster with intramuscular BNT162b2 in our current study (3821 BAU/mL) was similar to previous studies (3884 BAU/mL) [27]. Previous studies have also shown that the mix and match of the platform, namely CV/AZD1222, significantly elicited IgG anti-RBD at 28 days compared to CV/CV [28].…”

Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine

“…The delta and omicron variants have recently spread worldwide [3], and are causing breakthrough infection in vaccinated individuals [4, 5]. A preliminary study showed that vaccination of inactivated vaccine-vaccinated adults with a 15 μg-BNT162b2 mRNA dose elicited high immune responses against the SARS-CoV-2 delta variant [6, 7]. Our previous study demonstrated that individuals who received inactivated vaccines as their primary series achieved a high immune response against delta and omicron variants following receipt of a booster vaccination with the standard dose of BNT162b2 or mRNA-1273 [1].…”

Adverse Events Reporting Quality of Randomized Controlled Trials of COVID-19 Vaccine Using the CONSORT Criteria for Reporting Harms: A Systematic Review

“…The most common type of vaccine in these studies was viral vector, with the viral vectors used were adenovirus in 11 studies [17,22,23,26,29,33,34,36,39,40,54] and baculovirus in 2 studies [35,48]. Eighteen studies using vaccines with adjuvants: AlOH3/Algel-IMDG in 21 studies [18][19][20][27][28][29][30][31]35,45,48,51,52,[55][56][57]59,64,66,68,70], Matrix-M1 in three studies [21,63,74], AS03/CpG + Alum in one study [25], Af03/AS03 in one study [36], and MF59 in one study [42].…”

“…The second most significant domain that induced the 'some concern' was bias caused by deviations from the intended intervention (domain 2), in which 27 trials also appeared to have a probability of risk [24,33,37,44,[46][47][48]51,[53][54][55][58][59][60]62,64,[66][67][68][69][70][73][74][75][76][77]. Almost all of the bias on domain 2 is because of disclosure of the intervention, whether to patients and or the carer of the patients.…”