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Clinical MedicineIn-Press PreviewClinical trialsVaccines Open Access | 10.1172/jci.insight.187075

Randomised trial of same vs opposite arm co-administration of inactivated influenza and SARS-CoV-2 mRNA vaccines

Wen Shi Lee,1 Kevin J. Selva,1 Jennifer Audsley,2 Helen E. Kent,1 Arnold Reynaldi,3 Timothy E. Schlub,4 Deborah Cromer,3 David S. Khoury,3 Heidi Peck,5 Malet Aban,5 Mai Ngoc Vu,1 Ming Z. M. Zheng,1 Amy W. Chung,1 Marios Koutsakos,1 Hyon-Xhi Tan,1 Adam K. Wheatley,1 Jennifer A. Juno,1 Steven Rockman,1 Miles P. Davenport,3 Ian Barr,5 and Stephen J. Kent1

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Lee, W. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Koutsakos, M. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Tan, H. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Juno, J. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Rockman, S. in: JCI | PubMed | Google Scholar

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

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1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Barr, I. in: JCI | PubMed | Google Scholar |

1Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia

2Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia

3Kirby Institute, University of New South Wales, Kensington, Australia

4Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, Australia

5WHO Collaborating Centre for Reference and Research on Influenza, Royal Mel, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Find articles by Kent, S. in: JCI | PubMed | Google Scholar |

Published January 9, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.187075.
Copyright © 2025, Lee et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 9, 2025 - Version history
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Abstract

BACKGROUND. The immunogenicity of current influenza vaccines need improvement. Inactivated influenza and COVID-19 mRNA vaccines can be co-administered but randomized controlled trial data is lacking on whether the two vaccines are more immunogenic if given in the same or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when co-formulated and delivered together.

METHODS. We randomly assigned 56 adults to receive the Afluria quadrivalent inactivated influenza and Moderna monovalent SARS-CoV-2 XBB.1.5 mRNA vaccines, either in opposite arms or both in the same arm at the same site. The primary endpoint was the difference in median combined serum haemagglutination inhibition titre to the H1, H3 and B-Vic vaccine influenza strains after vaccination.

RESULTS. We found no significant difference in haemagglutination inhibition antibody levels between the groups (p = 0.30), with the same arm group having a 1.26-fold higher titre than the opposite arm group. There was no difference in analyses of antibodies to individual influenza strains, nor in nasal or saliva antibody levels. While both binding and neutralising antibody titres against SARS-CoV-2 were not significantly different between groups post-vaccination, there was a higher fold-change in BA.5 and ancestral strain neutralising antibodies in the opposite arm group.

CONCLUSION. Influenza vaccination is equivalently immunogenic if given in same or opposite arms as the SARS-CoV-2 vaccine, but it may be preferable to administer the SARS-CoV-2 vaccine at a different site to influenza vaccines.

TRIAL REGISTRATION. Australian New Zealand Clinical Trials Registry ACTRN12624000445572.

FUNDING. Australian National Health and Medical Research Council and Medical Research Future Fund.

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