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

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.

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Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Annette Fox reports financial support was provided by National Institutes of Health. Sheena Sullivan reports financial support was provided by National Institutes of Health. Adam Kucharski reports financial support was provided by National Institutes of Health. Annette Fox reports a relationship with Sanofi Aventis France that includes: funding grants. Helen Marshall reports a relationship with bioCSL that includes: funding grants. Helen Marshall reports a relationship with Pfizer Inc that includes: funding grants. Helen Marshall reports a relationship with GlaxoSmithKline Inc that includes: funding grants. Peter Wark reports a relationship with GlaxoSmithKline Inc that includes: funding grants. Peter Wark reports a relationship with Krystal Biotech, Inc. that includes: funding grants. Peter Wark reports a relationship with Vertex Pharmaceuticals Incorporated that includes: funding grants. Peter Wark reports a relationship with Sanofi that includes: funding grants. Sheena Sullivan reports a relationship with Pfizer Inc that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Sheena Sullivan reports a relationship with Moderna Inc that includes: consulting or advisory, non-financial support, and speaking and lecture fees. Sheena Sullivan reports a relationship with Seqirus Pty Ltd that includes: consulting or advisory, non-financial support, and speaking and lecture fees. Allen Cheng and Christopher Blyth are previous Chairs of the Australian Technical Advisory Group on Immunisation (ATAGI). The opinions in this study may not reflect the policy of ATAGI or the Australian Government regarding COVID-19 vaccines.