Robust antiviral humoral immunity induced by JN.1 monovalent mRNA vaccines against a broad range of SARS-CoV-2 Omicron subvariants including JN.1, KP.3.1.1 and XEC

As of November 2024, SARS-CoV-2 Omicron JN.1 subvariants, such as KP.2 (JN.1.11.1.2), KP.3 (JN.1.11.1.3), KP.3.1.1 (JN.1.11.1.3.1.1), and XEC -- a recombinant lineage between KS.1.1 (JN.13.1.1.1) and KP.3.3 (JN.1.11.1.3.3) -- have been circulating in several countries. To control the infection with SARS-CoV-2 Omicron JN.1 subvariants, JN.1 monovalent mRNA vaccines have been developed. Some previous reports showed that the JN.1 monovalent mRNA vaccine of Pfizer/BioNTech (US/Germany) increased antiviral humoral immunity against JN.1 subvariants and XEC. However, the efficacy of other available JN.1 monovalent mRNA vaccines (e.g., Daiichi-Sankyo, Japan) remains unassessed. To validate the antiviral efficacy induced by JN.1 mRNA vaccines, sera were collected from individuals vaccinated with Pfizer/BioNTech JN.1 mRNA vaccine (N=15) or Daiichi-Sankyo JN.1 mRNA vaccine (N=19) before and 3-4 weeks after vaccination. We then performed a neutralization assay using these sera and pseudoviruses. Both Pfizer/BioNTech JN.1 vaccine (2.4-to 8.0-fold, P=0.0001) and Daiichi-Sankyo JN.1 vaccine (2.3-to 13-fold, P=0.0001) boosted antiviral humoral immunity against all variants tested with statistical significance. While the Pfizer/BioNTech mRNA vaccine encodes the full-length JN.1 spike (S), the Daiichi-Sankyo mRNA vaccine encodes the receptor-binding domain of JN.1 S. Our data suggest that the receptor-binding domain of JN.1 S can effectively induce antiviral humoral immunity against JN.1 subvariants and XEC comparable to the full-length JN.1 S. However, it should be considered that the sizes of our cohorts are relatively small (<20 donors per cohort), and donor characteristics, such as age, sex, underlying disease status, and previous SARS-CoV-2 infection, may critically affect the experimental results. Future investigations with larger cohorts will address this concern. When compared to vaccination with JN.1 mRNA vaccines, our previous investigations showed that the natural infection of JN.1 and KP.3.3 elicited poorer antiviral humoral immunity against JN.1 and its subvariants. Our results suggest that the JN.1 mRNA vaccination more robustly induces antiviral humoral immunity against recent JN.1 subvariants than the natural infection of JN.1 subvariants regardless of manufacturer. Moreover, as we reported last year, the humoral immunity induced by XBB.1.5 monovalent mRNA vaccine against XBB.1.5 was weaker than that against ancestral B.1.1. However, in the case of JN.1 monovalent mRNA vaccine, here we showed that the 50% neutralization titer against XBB.1.5 is greater than that against ancestral B.1.1. These observations imply that immune imprinting has shifted from that biased toward pre-Omicron to that biased toward Omicron, depending on the time and/or number of immune stimuli (e.g., infection and/or vaccination).