Immunologic and Biophysical Features of the BNT162b2 JN.1- and KP.2-Adapted COVID-19 Vaccines DOI Creative Commons
Wei J. Chen, Kristin Tompkins,

I. Windsor

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT Vaccines remain a vital public health tool to reduce the burden of COVID-19. COVID-19 vaccines that are more closely matched circulating SARS-CoV-2 lineages elicit potent and relevant immune responses translate improved real-world vaccine effectiveness. The rise in prevalence Omicron JN.1 lineage, subsequent derivative sublineages such as KP.2 KP.3, coincided with reduced neutralizing activity effectiveness XBB.1.5-adapted vaccines. Here, we characterized biophysical immunologic attributes BNT162b2 JN.1- KP.2-adapted mRNA vaccine-encoded spike (S) protein immunogens. Biophysical interrogations S revealed structural consequences hallmark amino acid substitutions potential molecular mechanism escape employed by KP.2. candidates were evaluated for their immunogenicity when administered fourth or fifth doses BNT162b2-experienced mice primary series naïve mice. In both vaccine-experienced settings, conferred over XBB.1.5 against broad panel emerging sublineages, including predominant KP.3.1.1 XEC lineages. Antigenic mapping indicated greater antigenic overlap currently compared an vaccine. CD4 + CD8 T cell generally conserved across all three Together, data support selection 2024-25 formula. ONE-SENTENCE SUMMARY encoding prefusion proteins similar preclinical antibody sublineage pseudoviruses than those elicited past iterations licensed vaccines, thus demonstrating importance annual strain changes

Language: Английский

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants DOI Creative Commons
Qian Wang, Yicheng Guo, Anthony Bowen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 27, 2023

Summary COVID-19 vaccines have recently been updated with the spike protein of SARS-CoV-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report administration an monovalent mRNA vaccine (XBB.1.5 MV) uninfected individuals boosted serum virus-neutralization antibodies significantly not only (27.0-fold) currently dominant EG.5.1 (27.6-fold) also key like HV.1, HK.3, JD.1.1, JN.1 (13.3-to-27.4-fold). In previously infected by Omicron subvariant, neutralizing titers were highest levels (1,504-to-22,978) all viral variants tested. While immunological imprinting was still evident vaccines, it nearly as severe authorized bivalent BA.5 vaccine. Our findings strongly support official recommendation widely apply further protect public.

Language: Английский

Citations

43
Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial DOI Creative Commons

Juleen Gayed,

Oyeniyi Diya,

Francine S. Lowry

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 118 - 118

Published: Jan. 24, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy participants ≥12 years old (N = 412 (12–17 years, N 30; 18–55 174; >55 208)) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds 40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (ClinicalTrials.gov Identifier: NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all three sublineages month. These support favorable benefit-risk profile 30 μg. ClinicalTrials.gov NCT05997290

Language: Английский

Citations

24
Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study DOI

Katia Alves,

Karen L. Kotloff,

R. Scott McClelland

et al.

The Lancet Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial DOI Open Access

Juleen Gayed,

Oyeniyi Diya,

Francine S. Lowry

et al.

Published: Jan. 9, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 N=174; >55 N=208]) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds (N=40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all 3 sublineages month. These support favorable benefit-risk profile 30 μg. NCT05997290

Language: Английский

Citations

10
Neutralization of SARS‐CoV‐2 Omicron XBB.1.5 and JN.1 variants after COVID‐19 booster‐vaccination and infection DOI Creative Commons
David Niklas Springer, Jeremy V. Camp,

Stephan W. Aberle

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(7)

Published: July 1, 2024

Abstract SARS‐CoV‐2 Omicron lineages continue to emerge and evolve into new sublineages, causing infection waves throughout 2022 2023, which has been attributed immune escape. We examined neutralizing antibody responses the recently emerged JN.1 variant in comparison ancestral D614G BA.1, BA.2, BA.5, XBB.1.5 variants. tested 79 human sera from cohorts with different combinations of vaccinations infections, including 23 individuals who had repeatedly exposed Omicron. Individuals a monovalent vaccine booster or breakthrough robust levels against all variants tested; however, evaded antibodies after single BA.2 BA.5 infections. Moreover, non‐vaccinated cohort, serum demonstrated almost no cross‐neutralization activities D614G, JN.1. infections earlier These findings show that SARS‐CoV‐2‐immunity is heterogeneous, depending on emphasize importance considering immune‐backgrounds when evaluating novel

Language: Английский

Citations

8
BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults DOI Creative Commons
Sara Y. Tartof, Jeff Slezak, Timothy B. Frankland

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 28, 2023

ABSTRACT Importance Data describing the early additional protection afforded by recently recommended XBB1.5- adapted COVID-19 vaccines are limited. Objective We estimated association between receipt of BNT162b2 XBB1.5-adapted vaccine (Pfizer- BioNTech 2023–2024 formulation) and medically attended outcomes among adults ≥18 years age. Design, Setting, Participants performed a test-negative case-control study to compare odds cases controls in Kaiser Permanente Southern California health system October 11 December 10, 2023. Adjusted ratios (OR) 95% confidence intervals (CI) were from multivariable logistic regression models that adjusted for patient demographic clinical characteristics. Exposure The primary exposure was compared not receiving an any kind, regardless prior vaccination or SARS-CoV-2 infection history. also (non-XBB1.5-adapted) versions unvaccinated estimate remaining older vaccines. Main Outcomes Measures Cases those with positive polymerase chain reaction test, tested negative. Analyses done separately hospital admissions, emergency department (ED) urgent care (UC) encounters, outpatient visits. Results Among 4232 19,775 median age 54 years, ORs testing who received 30 days ago ( vs having kind) 0.37 (95% CI: 0.20–0.67) hospitalization, 0.42 (0.34–0.53) ED/UC visits, (0.27–0.66) Compared unvaccinated, had only did show significantly reduced risk outcomes, including admission. Conclusions Relevance Our findings reaffirm current recommendations broad age-based use annually updated given (1) provided significant against range (2) offered little, if any, protection, admission, number type doses received. KEY POINTS Questions Does offer admission ambulatory visits US kind? Do still provide unvaccinated? Findings (Pfizer-BioNTech during period when XBB sub-lineages predominant but JN.1 co-circulating rapidly increasing prevalence. Older Meaning

Language: Английский

Citations

15
Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission DOI Creative Commons
Mehdi Benlarbi,

Shilei Ding,

Étienne Bélanger

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: July 2, 2024

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring its subvariants. Omicron subvariants are responsible for the vast majority SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% circulating strains as January 2024. To better understand parameters involved in viral transmission, we characterized functional properties Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, JN.1. We tested their capacity to evade plasma-mediated recognition neutralization, binding angiotensin-converting enzyme (ACE2), susceptibility cold inactivation, processing, well impact temperature on Spike-ACE2 interaction. found that compared early wild-type (D614G) strain, most subvariants' evolved escape neutralization by plasma individuals who received a fifth dose bivalent (BA.1 or BA.4/5) mRNA vaccine improve ACE2 binding, particularly at low temperatures. Moreover, had best affinity all temperatures tested. processing is associated inactivation. Intriguingly, was significantly growth rates humans. Overall, report Spikes newly emerged relatively stable resistant present improved which associated, temperatures, rates.IMPORTANCEThe gave rise wide range variants harboring new mutations glycoproteins. Several factors have been transmission fitness such plasma-neutralization whether additional could be importance variants' characterize several glycoprotein presents an further temperature. interaction strongly rate, such, represent another parameter affecting transmission.

Language: Английский

Citations

5
Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera DOI Open Access
Wei Wang, Gitanjali Bhushan,

Stephanie Paz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 6, 2024

Abstract Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such rare due population immunity from infections and vaccinations. Here, we show that neutralization titers breadth matched human hamster pre-Omicron variant primary correlate well generate similar antigenic maps. The map shows modest drift among XBB sub-lineage variants, with JN.1 BA.4/BA.5 within the cluster, five six-fold differences between these XBB.1.5. Compared following only ancestral or bivalent vaccinations, post-vaccination infections, XBB.1.5 booster had broadest against although a five-fold titer difference was still observed variants. These findings suggest antibody coverage antigenically divergent could be improved vaccine antigen.

Language: Английский

Citations

3
Effectiveness of the BNT162b2 XBB.1.5-Adapted Vaccine Against COVID-19 Hospitalization Related to the JN.1 Variant in Europe: A Test-Negative Case-Control Study Using the id.Drive Platform DOI
Jennifer B. Nguyen, Marianna Mitratza, Hannah R. Volkman

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

2
Robust SARS-CoV-2-neutralizing antibodies sustained through 6 months post XBB.1.5 mRNA vaccine booster DOI Creative Commons
Qian Wang, Ian A. Mellis, Yicheng Guo

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101701 - 101701

Published: Aug. 28, 2024

Language: Английский

Citations

2