Immunogenicity and safety of DS-5670d, an mRNA-based COVID-19 vaccine targeting omicron XBB.1.5: Results from a phase 3, randomized, active-controlled study in adults and children aged ≥12 years DOI Creative Commons
Ami Kawamoto, Masaki Hashida,

Katsuyasu Ishida

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 15, 2024

Abstract Background Many people worldwide have now acquired immune responses against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) following previous vaccination and/or infection. As a result, national programs are implementing simplified schedule of single-dose administration and seasonal boosters. In this phase 3 non-inferiority study, we assessed immunogenicity safety single dose lipid nanoparticle-messenger ribonucleic acid vaccine DS-5670d, monovalent composition for 2023/24 season, containing an omicron XBB.1.5-derived antigen. Methods Findings Adults children aged ≥12 years were stratified according to their history both prior SARS-CoV-2 infection plus coronavirus disease 2019 (COVID-19) (subpopulation A), only B), C), or no either D), randomly assigned (1:1) receive DS-5670d BNT162b2 XBB.1.5. combined ABC subpopulations (DS-5670d, n = 362 vs BNT162b2, 363), adjusted geometric mean titer ratio blood neutralizing activity (omicron XBB.1.5) was 1.218 (95% confidence interval [CI], 1.059, 1.401) seroresponse rates 87.3% (DS-5670d) 82.9% (BNT162b2) with difference 4.5% CI, –0.70, 9.71). Both results exceeded prespecified margins study met primary endpoint. Immunogenicity data in overall ABCD population also criteria. There apparent differences age sex, analyses suggested that even unvaccinated persons achieved adequate response DS-5670d. major incidence severity adverse events between groups. Conclusions A immunogenically non-inferior acceptably safe without vaccination. Trial Registration Japan Registry Clinical Trials (jRCT2031230424) Author summary Why done? The global emergency pandemic is being superseded by annual immunization using updated reduce burden associated newly emerging variants. We conducted comparative two authorized compositions antigen derived from XBB.1.5, which recommended season. intended assess compared Japanese adults years. What did researchers do find? who had received vaccination, previously COVID-19, both, terms rates, not influenced sex. Among persons, those been exposed DS-5670d; however, group exposure at all too small properly evaluate. frequency groups, there DS-5670d-related serious events. these findings mean? has already widely administered Japan. new critical concerns suggesting it could be useful option. Taken together, studies evaluating other DS-5670, i.e., antigens different strains SARS-CoV-2, provide corroborating evidence DS-5670 platform can applied produce effective vaccines future strains.

Язык: Английский

Advances in the design and delivery of RNA vaccines for infectious diseases DOI Creative Commons
Abhijeet Lokras,

Thomas Rønnemoes Bobak,

Saahil Baghel

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 213, С. 115419 - 115419

Опубликована: Авг. 5, 2024

RNA medicines represent a paradigm shift in treatment and prevention of critical diseases global significance, e.g., infectious diseases. The highly successful messenger (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed at record speed during the disease 2019 pandemic. A consequence this is exceptionally shortened vaccine development times, which combination with adaptability makes technology attractive for pandemic preparedness. Here, we review state art design delivery based on different modalities, including linear mRNA, self-amplifying RNA, trans-amplifying circular RNA. We provide an overview clinical pipeline diseases, present analytical procedures, are paramount characterizing quality attributes guaranteeing their quality, discuss future perspectives using to combat pathogens beyond SARS-CoV-2.

Язык: Английский

Процитировано

11
Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids DOI Creative Commons

Johannes Bader,

Finn Brigger,

Jean‐Christophe Leroux

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер unknown, С. 115461 - 115461

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

4
Limitations of neutralizing antibody titers in COVID-19 vaccine efficacy trials and a call for additional correlates of protection DOI Creative Commons
Young Hoon Hwang, Dal‐Hee Min, Wan Beom Park

и другие.

Human Vaccines & Immunotherapeutics, Год журнала: 2025, Номер 21(1)

Опубликована: Март 7, 2025

The coronavirus disease (COVID-19) pandemic accelerated development of various vaccine platforms. Among them, mRNA vaccines played a crucial role in controlling the due to their swift and efficacy against virus variants. Despite success these vaccines, recent studies highlight challenges evaluating efficacy, especially individuals with prior COVID-19 infection. Weakened neutralizing antibody responses after additional doses are observed populations, raising concerns about using titers as sole immune correlate protection. While antibodies remain primary endpoint immunogenicity trials, they may not fully capture response populations widespread infection or vaccination. This review explores reduced previously infected individuals, impact on evaluation. It also offers recommendations for improving assessment, stressing incorporation markers such cell-mediated immunity enable more comprehensive understanding vaccine-induced immunity.

Язык: Английский

Процитировано

0
Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5–11 years: a phase 2/3, randomized, active-controlled study DOI Creative Commons

Rino Suzuki,

Miharu Suda,

Katsuyasu Ishida

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 2, 2024

Background DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding RBD original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 antigens) effective safe in adults. Data phase 2/3 active-controlled, non-inferiority, pediatric study evaluating third booster dose are reported here. Methods Children aged 5–11 years who had completed two-dose primary series BNT162b2 at least 3 months prior to enrolment were randomly assigned receive (20 µg mRNA) BNT1 62b2 (original/omicron BA.4-5; 10 on Day 1. The efficacy endpoint was blood neutralization geometric mean titer (GMT) (omicron variant BA.5.2.1) immune response rate (≥ 4-fold increase post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) 29. Results Among evaluable participants (DS-5670a/b, n = 74; BNT162b2, 75), adjusted GMT ratio 29 1.636 (95% CI, 1.221, 2.190). Immune rates ≥ 89% both vaccines; difference 2.6% –7.8, 13.8). prespecified non-inferiority margins exceeded, met endpoint. also demonstrated broad activity across recent sublineages no cases COVID-19 between Days 8–29 post-administration reported. There novel safety concerns population data cut-off. Conclusions Bivalent non-inferior terms immunogenicity, manageable profile, when administered as heterologous children years. Clinical trial registration https://jrct.niph.go.jp/ , identifier jRCT2031220665

Язык: Английский

Процитировано

2
Approved natural products-derived nanomedicines for disease treatment DOI
Xiaotong Li,

Yu-Ying Lai,

Guihong Wan

и другие.

Chinese Journal of Natural Medicines, Год журнала: 2024, Номер 22(12), С. 1100 - 1116

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

0
Analysis of B-cell receptor repertoire to evaluate the immunogenicity of SARS-CoV-2 RBD mRNA vaccine: MAFB-7256a (DS-5760d) DOI
Goh Ohji, Yohei Funakoshi, Kimikazu Yakushijin

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 21, 2024

ABSTRACT A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan the Spring of 2024 for preventing COVID-19. However, clinical efficacy data this vaccine are currently lacking. We previously established Quantification Antigen-specific Antibody Sequence (QASAS) method to assess response SARS-CoV-2 vaccination at level using B-cell receptor (BCR) repertoire assays Coronavirus Database (CoV-AbDab). Here, we used evaluate immunogenicity MAFB-7256a. analyzed repeated blood samples QASAS from three healthy volunteers before after vaccination. BCR increased rapidly one week post-vaccination then decreased, as with conventional vaccine. Notably, matched sequences specifically bound receptor-binding domain (RBD), no binding other epitopes. These results validate that is an effective exclusively induces antibodies specific RBD, demonstrating its targeted immunogenic effect.

Язык: Английский

Процитировано

0
Analysis of B-cell receptor repertoire to evaluate the immunogenicity of SARS-CoV-2 RBD mRNA vaccine: MAFB-7256a (DS-5670d) DOI Creative Commons
Goh Ohji, Yohei Funakoshi, Kimikazu Yakushijin

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 7, 2024

A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan the Spring of 2024 for prevention COVID-19. However, clinical efficacy data this vaccine are currently lacking. We previously established Quantification Antigen-specific Antibody Sequence (QASAS) method to assess response SARS-CoV-2 vaccination at level using B-cell receptor (BCR) repertoire assays Coronavirus Database (CoV-AbDab). Here, we used evaluate immunogenicity MAFB-7256a. analyzed repeated blood samples QASAS from three healthy volunteers before after vaccination. BCR increased rapidly one week post-vaccination then decreased, as with conventional vaccine. Notably, matched sequences specifically bound receptor-binding domain (RBD), no binding other epitopes. These results validate that is an effective exclusively induces antibodies specific RBD, demonstrating its targeted immunogenic effect.

Язык: Английский

Процитировано

0
Immunogenicity and safety of DS-5670d, an mRNA-based COVID-19 vaccine targeting omicron XBB.1.5: Results from a phase 3, randomized, active-controlled study in adults and children aged ≥12 years DOI Creative Commons
Ami Kawamoto, Masaki Hashida,

Katsuyasu Ishida

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 15, 2024

Abstract Background Many people worldwide have now acquired immune responses against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) following previous vaccination and/or infection. As a result, national programs are implementing simplified schedule of single-dose administration and seasonal boosters. In this phase 3 non-inferiority study, we assessed immunogenicity safety single dose lipid nanoparticle-messenger ribonucleic acid vaccine DS-5670d, monovalent composition for 2023/24 season, containing an omicron XBB.1.5-derived antigen. Methods Findings Adults children aged ≥12 years were stratified according to their history both prior SARS-CoV-2 infection plus coronavirus disease 2019 (COVID-19) (subpopulation A), only B), C), or no either D), randomly assigned (1:1) receive DS-5670d BNT162b2 XBB.1.5. combined ABC subpopulations (DS-5670d, n = 362 vs BNT162b2, 363), adjusted geometric mean titer ratio blood neutralizing activity (omicron XBB.1.5) was 1.218 (95% confidence interval [CI], 1.059, 1.401) seroresponse rates 87.3% (DS-5670d) 82.9% (BNT162b2) with difference 4.5% CI, –0.70, 9.71). Both results exceeded prespecified margins study met primary endpoint. Immunogenicity data in overall ABCD population also criteria. There apparent differences age sex, analyses suggested that even unvaccinated persons achieved adequate response DS-5670d. major incidence severity adverse events between groups. Conclusions A immunogenically non-inferior acceptably safe without vaccination. Trial Registration Japan Registry Clinical Trials (jRCT2031230424) Author summary Why done? The global emergency pandemic is being superseded by annual immunization using updated reduce burden associated newly emerging variants. We conducted comparative two authorized compositions antigen derived from XBB.1.5, which recommended season. intended assess compared Japanese adults years. What did researchers do find? who had received vaccination, previously COVID-19, both, terms rates, not influenced sex. Among persons, those been exposed DS-5670d; however, group exposure at all too small properly evaluate. frequency groups, there DS-5670d-related serious events. these findings mean? has already widely administered Japan. new critical concerns suggesting it could be useful option. Taken together, studies evaluating other DS-5670, i.e., antigens different strains SARS-CoV-2, provide corroborating evidence DS-5670 platform can applied produce effective vaccines future strains.

Язык: Английский

Процитировано

0