From September 5–11, 2024, 102 participants (18–55-year-olds, n = 51; > 55-year-olds, n = 51) at 8 sites in the United States received KP.2-adapted BNT162b2 (the corresponding date range for receipt of JN.1-adapted BNT162b2 in the comparator group was May 10–14, 2024). All but 1 participant who received KP-2-adapted BNT162b2 completed the 1-month postvaccination visit (an 18–55-year-old participant withdrew from the study; Figure S1).

In the safety population, 60.8% of participants were female, 74.5% were white, and the mean (SD) age at vaccination was 54.1 (15.1) years (Table 1). Overall, 91.2% of participants were SARS-CoV-2 positive at baseline, 90.2% had received previous COVID-19 vaccinations, and the median (range) duration since the previous COVID-19 vaccine was 13.3 (7.4–46.8) and 18.9 (5.5–47.3) months in 18–55-year-olds and > 55-year-olds, respectively.

Demographic characteristics for the evaluable immunogenicity population of the current cohort who received KP.2-adapted BNT162b2 and the comparator group who received JN.1-adapted BNT162b2 are provided in Table 2. The median (range) time from the most recent COVID-19 vaccination to receipt of study vaccination in the comparator group was 19.3 (5.6‒41.0) months and 9.8 (7.0‒35.4) months in 18–55-year-olds and > 55-year-olds, respectively (compared with 13.3 [7.4–46.8] months and 21.0 [5.5–47.3] months in the group of 18–55-year-old and > 55-year-old participants who received KP.2-adapted BNT162b2 in the current cohort).

Overall, 100 participants who received KP.2-adapted BNT162b2 were included in the evaluable immunogenicity population; two participants (one from each age group) were excluded because they did not have ≥ 1 valid and determinate immunogenicity result within the 28 to 42-day window after study vaccination, as specified in the protocol. Overall, 51 participants who received JN.1-adapted BNT162b2 in the comparator group were included in the evaluable immunogenicity population; three participants (18–55-year-olds, n = 1; > 55-year-olds, n = 2) were excluded from the evaluable immunogenicity population because they did not have ≥ 1 valid and determinate immunogenicity result within the protocol-specified window. In addition, the one 18 to 55-year-old participant did not receive study vaccination.

For KP.2-adapted BNT162b2, SARS-CoV-2 FFRNT 50% neutralizing titers against Omicron KP.2, JN.1, and KP.3 were substantially increased at 14 days and at 1 month after vaccination compared with baseline levels and were numerically higher at both postvaccination time points for the three lineages than those among the comparator group of participants who received JN.1-adapted BNT162b2 (Fig. 1; Table S2). Overall GMTs (95% CIs) at 1 month after receipt of KP.2-adapted BNT162b2 were 914.6 (684.7, 1221.7) for KP.2, 1021.8 (772.6, 1351.5) for JN.1, and 725.0 (543.0, 968.2) for KP.3. Corresponding values for JN.1-adapted BNT162b2 were 574.1 (407.8, 808.0) for KP.2, 728.2 (536.4, 988.6) for JN.1, and 437.4 (318.2, 601.3) for KP.3.

Serum-neutralizing GMTs (95% CIs) and GMFRs for all participants before and 14 days and 1 month after vaccination with KP.2-adapted or JN.1-adapted BNT162b2 30 μg to Omicron KP.2, JN.1, and KP.3. Data are for the evaluable immunogenicity population. Assay results < LLOQ were set to 0.5 × LLOQ. Values above bars are GMFRs from before to 14 days after vaccination (gray text) and from before to 1 month after vaccination (black italicized text). GMFRs with associated 95% CIs are in Table S2. 14d 14 days after vaccination, 1m 1 month after vaccination, FFRNT fluorescent focus reduction neutralization test, GMFR geometric mean fold rise, GMT geometric mean titer, LLOQ lower limit of quantitation

Overall GMFRs (95% CIs) from baseline to 1 month after receipt of KP.2-adapted BNT162b2 were 9.4 (7.0, 12.7) for KP.2, 7.8 (5.8, 10.4) for JN.1, and 9.2 (6.8, 12.3) for KP.3 (Fig. 1; Table S3). Corresponding GMFRs for JN.1-adapted BNT162b2 were 6.8 (5.0, 9.4) for KP.2, 5.7 (4.2, 7.7) for JN.1, and 7.0 (5.4, 9.0) for KP.3.

In both age groups, neutralizing titers generally peaked 14 days after vaccination and remained high 1 month after vaccination (Fig. 2; Table S2). One month after vaccination with KP.2-adapted BNT162b2, participants > 55 years of age had numerically higher GMTs against the 3 sublineages than those 18–55 years of age (KP.2, 1004 vs. 833; JN.1, 1114 vs. 937; KP.3, 777 vs. 677). For both age groups, GMTs at 14 days and at 1 month after vaccination with KP.2-adapted BNT162b2 were higher compared with JN.1-adapted BNT162b2 than with JN.1-adapted BNT162b2 against the 3 sublineages (KP.2: 14 days, 1084–1107 vs. 538–700; 1 month, 833–1004 vs. 486–655, JN.1: 1122–1186 vs. 708–871; 937–1114 vs. 698–756, and KP.3: 799–880 vs. 466–563; 677–777 vs. 403–470).

Serum-neutralizing GMTs (95% CIs) and GMFRs by age group before and 14 days and 1 month after vaccination with KP.2-adapted or JN.1-adapted BNT162b2 30 μg to Omicron KP.2 (a), JN.1 (b), and KP.3 (c). Data are for the evaluable immunogenicity population. Assay results < LLOQ were set to 0.5 × LLOQ. Numbers within the bars are GMTs. Values above bars are GMFRs from before to 14 days after vaccination (gray text) and from before to 1 month after vaccination (black italicized text). GMFRs with associated 95% CIs are in Table S2. 14d 14 days, 1m 1 month after vaccination, FFRNT fluorescent focus reduction neutralization test, GMFR geometric mean fold rise, GMT geometric mean titer, LLOQ lower limit of quantitation, Pre before vaccination

The percentages of overall participants with seroresponses were slightly higher against KP.2 (75% vs. 65%) and similar against JN.1 and KP.3 in participants receiving KP.2-adapted BNT162b2 compared with participants receiving JN.1-adapted BNT162b2 (Fig. 3).

Participants achieving seroresponse (95% CIs) 1 month after vaccination with KP.2-adapted BNT162b2 30 μg and JN.1-adapted BNT162b2 30 μg a overall and b by age group. Data are for the evaluable immunogenicity population. Seroresponse was defined as ≥ 4-fold rise from before vaccination in FFRNT 50% serum neutralizing titers. If participants had a baseline measurement < LLOQ, seroresponse was defined as a postvaccination assay result of ≥ 4 × LLOQ. FFRNT fluorescent focus reduction neutralization test, LLOQ lower limit of quantitation

Local reactions reported within 7 days of receipt of KP.2-adapted BNT162b2 were mild or moderate in severity (Fig. 4a). Pain at the injection site was the most common local reaction (58.8% of participants overall) and was more frequently reported among 18–55-year-olds (72.5%) than in > 55-year-olds (45.1%). The median onset and median duration of local reactions were both 1 to 3 days.

Local reactions (a) and systemic events (b) occurring within 7 days after receipt of KP.2-adapted BNT162b2 30 μg. Data are for the safety population. Numbers above the bars are the percentage of participants in each group reporting the specified local reaction or systemic event. The N values are 51, 51, and 102 for 18–55-year-olds, > 55-year-olds, and the total population, respectively

Systemic events reported within 7 days of receipt of KP.2-adapted BNT162b2 were also all mild to moderate in severity (Fig. 4b). The most frequently reported systemic events were fatigue, headache, and muscle pain (46.1%, 28.4%, and 21.6%, respectively, in the overall population), and all were reported more commonly among 18–55-year-olds than among > 55-year-olds (58.8% vs. 33.3%, 39.2% vs. 17.6%, and 33.3% vs. 9.8%). The median onset and median duration of systemic events were 2 to 4 days and 1 to 5 days, respectively.

Adverse events reported within 1 month of receipt of KP.2-adapted BNT162b2 were reported in 8.8% of participants overall and were more common among 18–55-year-olds (13.7%) than among > 55-year-olds (3.9%). One 18–55-year-old experienced an AE that was considered related to vaccination by the investigator (grade 1 bilateral breast tenderness that developed the day after vaccination and lasted 6 days in a female participant). No SAEs, AEs leading to withdrawal, or AESIs were reported. One case of COVID-19 was reported in an 18–55-year-old participant; this case occurred 22–28 days after vaccination and was of unknown lineage and not severe.