Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.
Date Issued
2022-10-04
Date Acceptance
2022-09-14
Citation
PLoS Pathogens, 2022, 18 (10), pp.1-20
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
20
Journal / Book Title
PLoS Pathogens
Volume
18
Issue
10
Copyright Statement
© 2022 Elliott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Sponsor
J P Moulton Charitable Foundation
The Sir Joseph Hotung Charitable Settlement
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36194628
PII: PPATHOGENS-D-22-00894
Grant Number
N/A
n/a
Subjects
Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
COVID-19
COVID-19 Vaccines
Humans
Immunity, Cellular
RNA
RNA, Messenger
SARS-CoV-2
Vaccination
Vaccines, Synthetic
mRNA Vaccines
Humans
Vaccines, Synthetic
RNA
RNA, Messenger
Antibodies, Viral
Vaccination
Immunity, Cellular
Antibodies, Neutralizing
COVID-19
SARS-CoV-2
COVID-19 Vaccines
mRNA Vaccines
BNT162 Vaccine
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Coverage Spatial
United States
Article Number
ARTN e1010885
Date Publish Online
2022-10-04