Effects of XFG-adapted mRNA vaccination on SARS-CoV-2 variant neutralisation
- 1Hannover Medical School
Abstract
SARS-CoV-2 antigenic evolution continues to challenge strain-matched vaccination. For the 2026-27 season, the European Medicines Agency (EMA) identified XFG as the preferred antigen within the JN.1 family and Comirnaty XFG was authorised in the European Union in July, 2026. We studied 22 participants who received 30 g of mRNA encoding XFG (Comirnaty XFG, BioNTech-Pfizer, Mainz, Germany) in September, 2026 and had paired serum available before vaccination and median 14 days afterwards. Median Wuhan-Hu-1 S1-specific IgG increased from 1600 BAU/mL (IQR 1118-2926) to 2914 BAU/mL (2117-4468), a 1{middle dot}8-fold increase. Median RBD-binding ED50 increased from 116 (51{middle dot}4-212) to 305{middle dot}6 (170{middle dot}8-434{middle dot}6) for LP.8.1 and from 354{middle dot}3 (129{middle dot}2-558{middle dot}2) to 832{middle dot}9 (429-1175) for NB.1.8.1, corresponding to 2{middle dot}6-fold and 2{middle dot}4-fold increases, respectively (all p<0{middle dot}0001). XFG-adapted vaccination increased neutralising activity against each tested variant. The GMT against XFG increased from 180 before vaccination to 894 afterwards (5{middle dot}0-fold), and that against RV.1.3 increased from 121 to 599 (4{middle dot}9-fold). GMTs increased from 117 to 386 for PQ.16.1.1 (3{middle dot}3-fold), from 101 to 316 for XFG.1.1 (3{middle dot}1-fold), from 629 to 1772 for LP.8.1 (2{middle dot}8-fold), from 221 to 611 for NB.1.8.1 (2{middle dot}8-fold), and from 228 to 642 for PJ.2.1 (2{middle dot}8-fold). Neutralisation of BA.3.2.2 increased more modestly, from GMT 78 to 126 (1{middle dot}6-fold; p=0{middle dot}0009). Pre-versus post-vaccination neutralisation titres differed significantly for all variants (p<0{middle dot}001). Despite the broad increase, post-vaccination neutralisation remained heterogeneous. Relative to LP.8.1, GMTs were 2{middle dot}0-fold lower for XFG, 2{middle dot}8-fold lower for PJ.2.1, 2{middle dot}9-fold lower for NB.1.8.1, 3{middle dot}0-fold lower for RV.1.3, 4{middle dot}6-fold lower for PQ.16.1.1, 5{middle dot}6-fold lower for XFG.1.1, and 14{middle dot}1-fold lower for BA.3.2.2. These findings provide early human immunogenicity data after XFG-adapted mRNA vaccination. The largest relative increases were observed for XFG and RV.1.3, whereas LP.8.1 remained the most strongly neutralised variant after Comirnaty XFG vaccination and BA.3.2.2 the least. This pattern suggests broad boosting of cross-reactive humoral immunity without elimination of between-variant differences. The small, extensively pre-immunised cohort, short follow-up, absence of a contemporaneous vaccine-comparator group, and use of a pseudovirus assay limit inference. Our data characterise early antibody binding and neutralisation but do not establish durability or clinical effectiveness.
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BibTeX
@misc{happle2026effects,
title = {{Effects of XFG-adapted mRNA vaccination on SARS-CoV-2 variant neutralisation}},
author = {C. Happle and M. Hoffmann and M. V. Stankov and N. Chen and I. Nehlmeier and L. Graichen and A.-S. Moldenhauer and T. Witte and S. Pöhlmann and A. Dopfer-Jablonka and G. M. Behrens},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.26364675},
url = {https://www.medrxiv.org/content/10.64898/2026.10.04.26364675v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Effects of XFG-adapted mRNA vaccination on SARS-CoV-2 variant neutralisation
AU - C. Happle
AU - M. Hoffmann
AU - M. V. Stankov
AU - N. Chen
AU - I. Nehlmeier
AU - L. Graichen
AU - A.-S. Moldenhauer
AU - T. Witte
AU - S. Pöhlmann
AU - A. Dopfer-Jablonka
AU - G. M. Behrens
PY - 2026
DA - 2026/10/04
PB - medRxiv
DO - 10.64898/2026.10.04.26364675
UR - https://www.medrxiv.org/content/10.64898/2026.10.04.26364675v1
AB - SARS-CoV-2 antigenic evolution continues to challenge strain-matched vaccination. For the 2026-27 season, the European Medicines Agency (EMA) identified XFG as the preferred antigen within the JN.1 family and Comirnaty XFG was authorised in the European Union in July, 2026. We studied 22 participants who received 30 g of mRNA encoding XFG (Comirnaty XFG, BioNTech-Pfizer, Mainz, Germany) in September, 2026 and had paired serum available before vaccination and median 14 days afterwards. Median Wuhan-Hu-1 S1-specific IgG increased from 1600 BAU/mL (IQR 1118-2926) to 2914 BAU/mL (2117-4468), a 1{middle dot}8-fold increase. Median RBD-binding ED50 increased from 116 (51{middle dot}4-212) to 305{middle dot}6 (170{middle dot}8-434{middle dot}6) for LP.8.1 and from 354{middle dot}3 (129{middle dot}2-558{middle dot}2) to 832{middle dot}9 (429-1175) for NB.1.8.1, corresponding to 2{middle dot}6-fold and 2{middle dot}4-fold increases, respectively (all p<0{middle dot}0001). XFG-adapted vaccination increased neutralising activity against each tested variant. The GMT against XFG increased from 180 before vaccination to 894 afterwards (5{middle dot}0-fold), and that against RV.1.3 increased from 121 to 599 (4{middle dot}9-fold). GMTs increased from 117 to 386 for PQ.16.1.1 (3{middle dot}3-fold), from 101 to 316 for XFG.1.1 (3{middle dot}1-fold), from 629 to 1772 for LP.8.1 (2{middle dot}8-fold), from 221 to 611 for NB.1.8.1 (2{middle dot}8-fold), and from 228 to 642 for PJ.2.1 (2{middle dot}8-fold). Neutralisation of BA.3.2.2 increased more modestly, from GMT 78 to 126 (1{middle dot}6-fold; p=0{middle dot}0009). Pre-versus post-vaccination neutralisation titres differed significantly for all variants (p<0{middle dot}001). Despite the broad increase, post-vaccination neutralisation remained heterogeneous. Relative to LP.8.1, GMTs were 2{middle dot}0-fold lower for XFG, 2{middle dot}8-fold lower for PJ.2.1, 2{middle dot}9-fold lower for NB.1.8.1, 3{middle dot}0-fold lower for RV.1.3, 4{middle dot}6-fold lower for PQ.16.1.1, 5{middle dot}6-fold lower for XFG.1.1, and 14{middle dot}1-fold lower for BA.3.2.2. These findings provide early human immunogenicity data after XFG-adapted mRNA vaccination. The largest relative increases were observed for XFG and RV.1.3, whereas LP.8.1 remained the most strongly neutralised variant after Comirnaty XFG vaccination and BA.3.2.2 the least. This pattern suggests broad boosting of cross-reactive humoral immunity without elimination of between-variant differences. The small, extensively pre-immunised cohort, short follow-up, absence of a contemporaneous vaccine-comparator group, and use of a pseudovirus assay limit inference. Our data characterise early antibody binding and neutralisation but do not establish durability or clinical effectiveness.
ER -