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. 2023 Sep 27;14(1):6041.
doi: 10.1038/s41467-023-41678-9.

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease

Kevin Yau  1   2 , Alexandra Kurtesi  3 , Freda Qi  3 , Melanie Delgado-Brand  3 , Tulunay R Tursun  3 , Queenie Hu  3 , Miten Dhruve  4 , Christopher Kandel  5 , Omosomi Enilama  6 , Adeera Levin  7 , Yidi Jiang  8 , W Rod Hardy  3 , Darren A Yuen  9 , Jeffrey Perl  9 , Christopher T Chan  2 , Jerome A Leis  10 , Matthew J Oliver  1   11 , Karen Colwill  3 , Anne-Claude Gingras  3   12 , Michelle A Hladunewich  13   14
Affiliations

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease

Kevin Yau et al. Nat Commun. .

Abstract

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.

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Conflict of interest statement

A.L. reports being a scientific advisor to, or member of, AstraZeneca, Bayer, Boehringer-Ingelheim, Canadian Journal of Kidney Health and Disease, Canadian Institutes of Health Research, Certa, Chinook Therapeutics, Johnson and Johnson, Kidney Foundation of Canada, National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Otsuka, Reata, Retrophin, and The George Institute; receiving research funding from AstraZeneca, Boehringer-Ingelheim, Canadian Institute of Health Research, Janssen, Johnson and Johnson, Kidney Foundation of Canada, Merck, NIDDK, NIH, Ortho Biotech, Otsuka, and Oxford Clinical Trials; and having consultancy agreements with Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Johnson and Johnson/Jansen, Reata, and Retrophin (unrelated to the submitted work). D.Y. reports being a scientific co-founder and consultant for Fibrocor Therapeutics; receiving speaking honoraria and/or consultancy fees from AstraZeneca, GlaxoSmithKline, and Vivace Therapeutics (unrelated to the submitted work). J.P. reported receiving speaking honoraria and consultancy fees from Baxter Healthcare; grants from Agency for Healthcare Research and Quality grant support; speaking honoraria from Fresenius Medical Care, AstraZeneca, Davita Healthcare, and US Renal Care; and consultancy fees from LiberDi Dialysis (unrelated to the submitted work). J.L. has received payment for expert testimony upon request of hospitals of the Ontario Hospital Association, Ministry of Attorney General of Ontario, and Seneca College (unrelated to the submitted work). A.C.G. has received research funds from a research contract with Providence Therapeutics Holdings, Inc for other projects, participated in the COVID-19 Immunity Task Force Immune Science and Testing working party, chaired the CIHR Institute of Genetics Advisory Board, and chairs the SAB of the National Research Council of Canada Human Health Therapeutics Board. M.O. and M.H are contracted Medical Leads at the Ontario Renal Network, Ontario Health. Matthew Oliver is owner of Oliver Medical Management Inc., which licenses Dialysis Management Analysis and Reporting System software. He has received honoraria for speaking from Baxter Healthcare (unrelated to the submitted work). M.H. reports receiving grants from Pfizer for a study in focal segmental glomerulosclerosis, Ionis, Calliditas and Chinook for studies in Immunoglobulin A nephropathy, and Roche for a preeclampsia study (unrelated to the submitted work). No other competing interests were declared.

Figures

Fig. 1
Fig. 1. Neutralizing capacity against SARS-CoV-2 Omicron subvariants prior to and 1 month following bivalent mRNA COVID-19 vaccination.
Log10 ID50 greater than 0 was considered detectable neutralization capacity. Dots represent individual serum samples collected (n = 98 for each time point). Solid red line indicates median level. Fold change in neutralization capacity was 7.3-fold lower for BA.1, 8.3-fold lower for BA.5 and 45.8-fold lower for BQ.1.1 and 48.2-fold lower for XBB.1.5. in comparison to the wild-type (D614G) ancestral strain. Comparison prior to and following bivalent vaccination were evaluated using Wilcoxon signed-rank test with a two-sided p-value. No adjustments were made for multiple comparisons.
Fig. 2
Fig. 2. Neutralizing antibodies against wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 prior to and following bivalent vaccination.
a Stratified by vaccine type BNT162b2 BA.4/5 (n = 26) versus mRNA-1273 BA.1 (n = 72). Increases in neutralizing antibody levels were not significantly different by bivalent vaccine type for any subvariant after adjustment for anti-nucleocapsid positivity, hemodialysis versus kidney transplant recipient, and number of vaccine doses or (b) stratified by anti-nucleocapsid IgG seropositivity (n = 40) as a marker of prior COVID-19 infection versus seronegative (n = 58). Neutralizing antibody against Omicron subvariants were higher among those with anti-nucleocapsid seropositivity against wild-type (D614G) (P = 0.047), BA.1 (P = 0.0048), BA.5 (P = 0.029), BQ.1.1 (P = 0.018), and XBB.1.5 (P = 0.014) after adjusting for number of doses, vaccine type, patient type, and timepoint; or (c) stratified by patient type (hemodialysis n = 83) versus kidney transplant (n = 15). Solid red line indicates median level. Dots represent individual serum samples collected (n = 98 for each time point). Results were analysed using a linear mixed effects model, with a two-sided p-value. No adjustments were made for multiple comparisons.
Fig. 3
Fig. 3. Neutralizing antibodies against wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 by bivalent vaccine type after exclusion of participants with a positive anti-nucleocapsid antibody.
Solid red line indicates median level. Dots represent individual serum samples collected (n = 58 prior to bivalent vaccination [BNT162b2 BA.4/5 n = 14; mRNA-1273 n = 44], n = 52 one-month post-vaccination [BNT162b2 BA.4/5 n = 13; mRNA-1273 n = 39].
Fig. 4
Fig. 4. Difference in neutralizing antibodies against wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 by total number of COVID-19 vaccine doses.
There was no significant difference in neutralizing antibodies against any subvariant in those receiving 4 (n = 8) versus 5 doses (n = 90). Solid red line indicates median level. Dots represent individual serum samples collected (n = 98 for each timepoint).
See this image and copyright information in PMC

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