PMID- 36194628 OWN - NLM STAT- MEDLINE DCOM- 20221018 LR - 20240320 IS - 1553-7374 (Electronic) IS - 1553-7366 (Print) IS - 1553-7366 (Linking) VI - 18 IP - 10 DP - 2022 Oct TI - Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines. PG - e1010885 LID - 10.1371/journal.ppat.1010885 [doi] LID - e1010885 AB - 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-y 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 naive 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. FAU - Elliott, Tamara AU - Elliott T AUID- ORCID: 0000-0001-8232-9413 AD - Department of Infectious Disease, Imperial College London, United Kingdom. AD - Imperial College Healthcare NHS Trust, London, United Kingdom. AD - Imperial College NIHR BRC, London, United Kingdom. FAU - Cheeseman, Hannah M AU - Cheeseman HM AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - Evans, Abbey B AU - Evans AB AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - Day, Suzanne AU - Day S AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - McFarlane, Leon R AU - McFarlane LR AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - O'Hara, Jessica AU - O'Hara J AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - Kalyan, Mohini AU - Kalyan M AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - Amini, Fahimah AU - Amini F AD - Department of Infectious Disease, Imperial College London, United Kingdom. FAU - Cole, Tom AU - Cole T AD - Department of Infectious Disease, Imperial College London, United Kingdom. AD - Imperial College Healthcare NHS Trust, London, United Kingdom. FAU - Winston, Alan AU - Winston A AD - Department of Infectious Disease, Imperial College London, United Kingdom. AD - Imperial College Healthcare NHS Trust, London, United Kingdom. FAU - Fidler, Sarah AU - Fidler S AD - Department of Infectious Disease, Imperial College London, United Kingdom. AD - Imperial College Healthcare NHS Trust, London, United Kingdom. AD - Imperial College NIHR BRC, London, United Kingdom. FAU - Pollock, Katrina M AU - Pollock KM AD - Department of Infectious Disease, Imperial College London, United Kingdom. AD - Imperial College Healthcare NHS Trust, London, United Kingdom. FAU - Harker, James A AU - Harker JA AD - National Heart and Lung Institute, London, United Kingdom. FAU - Shattock, Robin J AU - Shattock RJ AD - Department of Infectious Disease, Imperial College London, United Kingdom. LA - eng GR - MC_PC_19076/MRC_/Medical Research Council/United Kingdom GR - MR/L00528X/1/MRC_/Medical Research Council/United Kingdom GR - MR/W024977/1/MRC_/Medical Research Council/United Kingdom GR - DH_/Department of Health/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221004 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (RNA, Messenger) RN - 0 (Vaccines, Synthetic) RN - 0 (mRNA Vaccines) RN - 63231-63-0 (RNA) RN - N38TVC63NU (BNT162 Vaccine) RN - SARS-CoV-2 variants SB - IM MH - Antibodies, Neutralizing MH - Antibodies, Viral MH - BNT162 Vaccine MH - *COVID-19/prevention & control MH - *COVID-19 Vaccines MH - Humans MH - Immunity, Cellular MH - RNA MH - RNA, Messenger MH - SARS-CoV-2 MH - Vaccination MH - Vaccines, Synthetic MH - mRNA Vaccines PMC - PMC9565686 COIS- The authors have declared that no competing interests exist. EDAT- 2022/10/05 06:00 MHDA- 2022/10/19 06:00 PMCR- 2022/10/04 CRDT- 2022/10/04 13:43 PHST- 2022/05/18 00:00 [received] PHST- 2022/09/14 00:00 [accepted] PHST- 2022/10/14 00:00 [revised] PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/10/19 06:00 [medline] PHST- 2022/10/04 13:43 [entrez] PHST- 2022/10/04 00:00 [pmc-release] AID - PPATHOGENS-D-22-00894 [pii] AID - 10.1371/journal.ppat.1010885 [doi] PST - epublish SO - PLoS Pathog. 2022 Oct 4;18(10):e1010885. doi: 10.1371/journal.ppat.1010885. eCollection 2022 Oct.