Safety and Immunogenicity of Monovalent Omicron KP.2-Adapted BNT162b2 COVID-19 Vaccine in Adults: Single-Arm Substudy from a Phase 2/3 Trial

Abstract

Introduction: COVID-19 continues to cause substantial health burden, particularly among vulnerable populations. Vaccines remain a vital tool in preventing severe disease outcomes. As the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve; therefore, updates may be needed to closely match COVID-19 vaccine composition to predominant circulating lineages to confer optimal protection.

Methods: In this cohort from a substudy of an ongoing phase 2/3 trial, 102 healthy adults (18‒55 and > 55 years of age, n = 51 each) were vaccinated with Omicron KP.2-adapted BNT162b2. Serum neutralizing titers against Omicron KP.2, JN.1, and KP.3 were assessed before and through 1 month after vaccination. Immunogenicity in KP.2-adapted BNT162b2 recipients was compared with participants who received JN.1-adapted BNT162b2 in an earlier cohort of this substudy. Local reactions and systemic events through 7 days and adverse events (AEs) through 1 month are reported.

Results: One month after vaccination, KP.2-adapted BNT162b2-elicited neutralizing titers against Omicron KP.2, JN.1, and KP.3 were numerically higher than those induced by JN.1-adapted BNT162b2. Geometric mean fold rises from before to 1 month after vaccination were numerically higher in those who received KP.2-adapted BNT162b2 compared with those who received JN.1-adapted BNT162b2 (9.4 vs. 6.8 for KP.2; 7.8 vs. 5.7 for JN.1; 9.2 vs. 7.0 for KP.3). Percentages of participants with seroresponses were numerically higher against KP.2 after KP.2-adapted BNT162b2 than JN.1-adapted BNT162b2 (75% vs. 65%) and similar against JN.1 and KP.3 for both vaccines (69% vs. 67% for JN.1; 74% vs. 73% for KP.3). Local reactions and systemic events were all mild to moderate in severity, AEs were infrequent, and no serious AEs or AEs leading to withdrawal were reported.

Conclusions: Collectively, these immunogenicity, safety, and tolerability data support administration of KP.2-adapted BNT162b2 to protect against contemporaneous circulating lineages.

Gov identifier: NCT05997290.

Keywords: BNT162b2; Booster; COVID-19; Lineage; Omicron KP.2; SARS-CoV-2 vaccine; Sublineage; Variant adapted.

Fig. 1

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

Fig. 2

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

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

Fig. 4

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