Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

Suvimol Niyomnaitham; Suparat Atakulreka; Patimaporn Wongprompitak; Katherine Kradangna Copeland; Zheng Quan Toh; Paul V Licciardi; Kanjana Srisutthisamphan; Laddawan Jansarikit; Kulkanya Chokephaibulkit

doi:10.3389/fimmu.2022.1080791

Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

Front Immunol. 2023 Jan 17:13:1080791. doi: 10.3389/fimmu.2022.1080791. eCollection 2022.

Authors

Affiliations

¹ Siriraj Institute of Clinical Research, Bangkok, Thailand.
² Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁴ Department of Biological Sciences, Faculty of Science, Mahidol University International College, Nakhon Pathom, Thailand.
⁵ Infection and Immunology, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁶ Department of Pediatrics, The University of Melbourne, Parkville, VIC, Australia.
⁷ National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science Development Agency (NSTDA), Pathumthani, Thailand.
⁸ Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Introduction: This phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19.

Methods: Participants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools.

Results: Immunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P < 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P < 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts.

Discussion: We concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks.

Keywords: COVID-19 vaccination; Thailand; accelerated regimen; fractional dose; heterologous regimen; immunogenicity; intradermal.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

BNT162 Vaccine*
COVID-19 Vaccines / adverse effects
COVID-19* / prevention & control
Humans
Immunoglobulin G
SARS-CoV-2

Substances

sinovac COVID-19 vaccine
spike protein, SARS-CoV-2
BNT162 Vaccine
COVID-19 Vaccines
Immunoglobulin G

Grants and funding

We would like to acknowledge funding from the Health Systems Research Institute (Grant Number: 65-009). The funder played no role in the conceptualization or analysis of this research article.