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.

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in COVID-19.Since the end of October 2021, this serious illness has infected more than 242 million patients and has been the cause of over 5 million deaths worldwide

  • Recent studies have suggested that intradermal vaccination with reciprocal doses (1:5 and 1:10) of mRNA-1273 (Moderna) provided similar antibody responses compared to a full dose of conventional intramuscular injections [21]

  • This study highlights the differences in humoral and cellular immune responses between heterologous vaccination with a conventional intramuscular booster and fractional intradermal booster of the mRNA vaccine (BNT162b2) from healthy volunteers having been administered with two doses of the inactivated SARS-CoV-2 vaccine

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Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in COVID-19. Since the end of October 2021, this serious illness has infected more than 242 million patients and has been the cause of over 5 million deaths worldwide. Recent studies have shown the efficacy of an mRNA-based vaccine (BNT162b2), and a replication-deficient simian adenovirus vector (ChAdOx1 nCoV-19) against the Delta variant of SARS-CoV-2. Vaccine prioritisation and mass administration have been proven to be unsuccessful in the countries with limited vaccine supplies, and have constricted vaccine platforms [15] This current study focused on boosting immunity in addition to the existing inactivated SARS-CoV-2 (CoronaVac) vaccine regimen. Recent studies have suggested that intradermal vaccination with reciprocal doses (1:5 and 1:10) of mRNA-1273 (Moderna) provided similar antibody responses compared to a full dose of conventional intramuscular injections [21]. We conducted the safety and immunogenicity study in healthy adults who had received a conventional two dosage of inactivated SARS-CoV-2 vaccine (CoronaVac) with an intradermal booster, using a reciprocal dosage of BNT162b2.

Study Participants
Immediate and Delay Adverse Events
Study Procedures
Immediate and Delayed Adverse Events
Sample Processing
Quantification of SARS-CoV-2 Anti-S RBD Antibodies
Ex vivo IFN-γ ELISpot Assays
Statistical Analysis
Findings
Discussion
Conclusions
Full Text
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