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Randomized trial of same- versus opposite-arm coadministration of inactivated influenza and SARS-CoV-2 mRNA vaccines
Wen Shi Lee, Kevin J. Selva, Jennifer Audsley, Helen E. Kent, Arnold Reynaldi, Timothy E. Schlub, Deborah Cromer, David S. Khoury, Heidi Peck, Malet Aban, Mai Ngoc Vu, Ming Z.M. Zheng, Amy W. Chung, Marios Koutsakos, Hyon-Xhi Tan, Adam K. Wheatley, Jennifer A. Juno, Steven Rockman, Miles P. Davenport, Ian Barr, Stephen J. Kent
Wen Shi Lee, Kevin J. Selva, Jennifer Audsley, Helen E. Kent, Arnold Reynaldi, Timothy E. Schlub, Deborah Cromer, David S. Khoury, Heidi Peck, Malet Aban, Mai Ngoc Vu, Ming Z.M. Zheng, Amy W. Chung, Marios Koutsakos, Hyon-Xhi Tan, Adam K. Wheatley, Jennifer A. Juno, Steven Rockman, Miles P. Davenport, Ian Barr, Stephen J. Kent
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Clinical Research and Public Health Clinical trials Vaccines

Randomized trial of same- versus opposite-arm coadministration of inactivated influenza and SARS-CoV-2 mRNA vaccines

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Abstract

BACKGROUND The immunogenicity of current influenza vaccines needs improvement. Inactivated influenza and COVID-19 mRNA vaccines can be coadministered, but randomized controlled trial data are lacking on whether the 2 vaccines are more immunogenic if given in the same arm or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when coformulated and codelivered.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 hemagglutination inhibition titer to the H1, H3, and B-Vic vaccine influenza strains after vaccination.RESULTS We found no significant difference in hemagglutination inhibition antibody levels between the groups (P = 0.30), with the same-arm group having a 1.26-fold higher titer than the opposite-arm group. There were no differences in analyses of antibodies against individual influenza strains or in nasal or saliva antibody levels. While both binding and neutralizing antibody titers against SARS-CoV-2 were not significantly different between groups postvaccination, there was a higher fold-change in BA.5 and ancestral strain neutralizing antibodies in the opposite-arm group.CONCLUSION Influenza vaccination is equivalently immunogenic if given in the same arm 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 from influenza vaccines.TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12624000445572.FUNDING Australian National Health and Medical Research Council, Australian Medical Research Future Fund, and National Institutes of Health (UH2AI176172).

Authors

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

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Figure 2

Plasma antibody responses to influenza following coadministration of COVID-19 mRNA boosters and inactivated influenza vaccines in the same or opposite arms.

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Plasma antibody responses to influenza following coadministration of COV...
(A and B) Geometric means of HI titers across 3 strains (H1N1, H3N2, and B-VIC) included in the influenza vaccine for both the same-arm (n = 27; red circles) and opposite-arm (n = 28; blue squares) groups. Box-and-whisker plots compare either (A) responses at day 28 alone or (B) the fold-change in geometric means of HI titers from day 0 to day 28 postvaccination. Statistical significance was calculated between groups using the 2-tailed Mann-Whitney U test. (C) Line graphs depict the geometric mean HI titers for each group at days 0, 6, and 28 postvaccination (averaged across individuals and the 3 vaccine strains H1N1, H3N2, and B-VIC). (D) Line graphs show the geometric mean HI titers for each vaccine strain (H1N1, H3N2, B-VIC, B-YAM), averaged across individuals. The same-arm cohort is depicted in solid lines, while the opposite-arm cohort is in dotted lines. (E) Fold-change in plasma IgG antibody binding levels against recombinant HA proteins from different circulating influenza strains as measured by bead-based multiplex (final dilution 1:25,600). Vaccine strains are indicated in bold. Statistical significance was calculated between groups using the 2-tailed Mann-Whitney U test. For box-and-whisker plots, central lines indicate medians, boxes indicate 25th and 75th percentiles, and whiskers indicate range (minimum and maximum).

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