Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines

Yi Liu; Stephany Sánchez-Ovando; Louise Carolan; Leslie Dowson; Arseniy Khvorov; A Jessica Hadiprodjo; Yeu Yang Tseng; Catherine Delahunty; Ameneh Khatami; Marion Macnish; Sonia Dougherty; Michelle Hagenauer; Kathryn E Riley; Ajay Jadhav; Joanne Harvey; Marti Kaiser; Suja Mathew; David Hodgson; Vivian Leung; Kanta Subbarao; Allen C Cheng; Kristine Macartney; Archana Koirala; Helen Marshall; Julia Clark; Christopher C Blyth; Peter Wark; Adam J Kucharski; Sheena G Sullivan; Annette Fox

doi:10.1016/j.vaccine.2023.10.034

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines

Vaccine. 2023 Nov 22;41(48):7192-7200. doi: 10.1016/j.vaccine.2023.10.034. Epub 2023 Oct 28.

Authors

Yi Liu¹, Stephany Sánchez-Ovando¹, Louise Carolan², Leslie Dowson³, Arseniy Khvorov¹, A Jessica Hadiprodjo¹, Yeu Yang Tseng¹, Catherine Delahunty⁴, Ameneh Khatami⁵, Marion Macnish⁶, Sonia Dougherty⁷, Michelle Hagenauer⁸, Kathryn E Riley⁹, Ajay Jadhav¹⁰, Joanne Harvey⁶, Marti Kaiser⁸, Suja Mathew⁹, David Hodgson¹¹, Vivian Leung³, Kanta Subbarao¹², Allen C Cheng⁸, Kristine Macartney⁵, Archana Koirala⁵, Helen Marshall⁹, Julia Clark⁷, Christopher C Blyth¹³, Peter Wark⁴, Adam J Kucharski¹¹, Sheena G Sullivan¹⁴, Annette Fox¹⁵

Affiliations

¹ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
² WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
³ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁴ Immune Health Program, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
⁵ The Children's Hospital at Westmead, Sydney Children's Hospital Network, National Centre for Immunisation Research and Surveillance, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
⁶ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.
⁷ Queensland Children's Hospital, Children's Health Queensland Hospital and Health Service, and University of Queensland, Brisbane, Australia.
⁸ Alfred Health, Monash Health and Monash University, Melbourne, Australia.
⁹ Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide, Australia; Division of Paediatric Medicine, Women's and Children's Health Network, Adelaide, Australia.
¹⁰ The Children's Hospital at Westmead, Sydney Children's Hospital Network, National Centre for Immunisation Research and Surveillance, Sydney, Australia.
¹¹ Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
¹² Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹³ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia; School of Medicine, University of Western Australia, Perth Children's Hospital, and Department of Microbiology, PathWest Laboratory Medicine, QEII medical centre, Perth, Australia.
¹⁴ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Epidemiology, University of California, Los Angeles, USA.
¹⁵ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Electronic address: annette.fox@unimelb.edu.au.

PMID: 37903679
DOI: 10.1016/j.vaccine.2023.10.034

Abstract

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

Keywords: Antibody; B cells; COVID-19; SARS-CoV-2; Vaccine; Vector; mRNA.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Humans
Pandemics / prevention & control
SARS-CoV-2
Viral Vaccines*

Substances

COVID-19 Vaccines
BNT162 Vaccine
ChAdOx1 nCoV-19
Viral Vaccines
Antibodies
Antibodies, Viral

Associated data

ClinicalTrials.gov/NCT05110911

Grants and funding

R01 AI141534/AI/NIAID NIH HHS/United States