Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

ConquerRSV Study Group; Eleanor Wilson; Jaya Goswami; Abdullah H Baqui; Pablo A Doreski; Gonzalo Perez-Marc; Khalequ Zaman; Jorge Monroy; Christopher J A Duncan; Mugen Ujiie; Mika Rämet; Lina Pérez-Breva; Ann R Falsey; Edward E Walsh; Rakesh Dhar; Lauren Wilson; Jiejun Du; Parinaz Ghaswalla; Archana Kapoor; Lan Lan; Shraddha Mehta; Runa Mithani; Catherine A Panozzo; Alana K Simorellis; Barbara J Kuter; Florian Schödel; Wenmei Huang; Caroline Reuter; Karen Slobod; Sonia K Stoszek; Christine A Shaw; Jacqueline M Miller; Rituparna Das; Grace L Chen

doi:10.1056/NEJMoa2307079

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

ConquerRSV Study Group
, Eleanor Wilson
, Jaya Goswami
, Abdullah H Baqui
, Pablo A Doreski
, Gonzalo Perez-Marc
, Khalequ Zaman
, Jorge Monroy
, Christopher J A Duncan
, Mugen Ujiie
, Mika Rämet
, Lina Pérez-Breva
, Ann R Falsey
, Edward E Walsh
, Rakesh Dhar
, Lauren Wilson
, Jiejun Du
, Parinaz Ghaswalla
, Archana Kapoor
, Lan Lan

Shraddha Mehta, Runa Mithani, Catherine A Panozzo, Alana K Simorellis, Barbara J Kuter, Florian Schödel, Wenmei Huang, Caroline Reuter, Karen Slobod, Sonia K Stoszek, Christine A Shaw, Jacqueline M Miller, Rituparna Das, Grace L Chen

Biosciences

Research output: Contribution to journal › Article › Scientific › peer-review

317 Citations (Scopus)

1 Downloads (Pure)

Abstract

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.

METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.

RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.

CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

Original language	English
Pages (from-to)	2233-2244
Number of pages	12
Journal	The New England Journal of Medicine
Volume	389
Issue number	24
DOIs	https://doi.org/10.1056/NEJMoa2307079
Publication status	Published - 13 Dec 2023
Publication type	A1 Journal article-refereed

Keywords

Aged
Humans
Antibodies, Viral
Double-Blind Method
Respiratory Syncytial Virus Infections/epidemiology
Respiratory Syncytial Virus, Human/genetics
Respiratory Tract Diseases/diagnosis
Treatment Outcome
mRNA Vaccines/adverse effects
Respiratory Syncytial Virus Vaccines/adverse effects
Middle Aged

Publication forum classification

Publication forum level 3

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1056/NEJMoa2307079

Wilson_NEJM_Manuscript_clean
This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
Accepted author manuscript, 752 KBLicence: Unspecified

https://urn.fi/URN:NBN:fi:tuni-202504043286Licence: Unspecified

Cite this

ConquerRSV Study Group, Wilson, E., Goswami, J., Baqui, A. H., Doreski, P. A., Perez-Marc, G., Zaman, K., Monroy, J., Duncan, C. J. A., Ujiie, M., Rämet, M., Pérez-Breva, L., Falsey, A. R., Walsh, E. E., Dhar, R., Wilson, L., Du, J., Ghaswalla, P., Kapoor, A., ... Chen, G. L. (2023). Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. The New England Journal of Medicine, 389(24), 2233-2244. https://doi.org/10.1056/NEJMoa2307079

@article{bce87075269a4333bc8a6f01296d1e78,

title = "Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults",

abstract = "BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50\% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7\% (95.88\% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4\% (96.36\% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4\% (95\% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7\% vs. 16.2\%) and of systemic adverse reactions (47.7\% vs. 32.9\%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8\% of the participants in each trial group.CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).",

keywords = "Aged, Humans, Antibodies, Viral, Double-Blind Method, Respiratory Syncytial Virus Infections/epidemiology, Respiratory Syncytial Virus, Human/genetics, Respiratory Tract Diseases/diagnosis, Treatment Outcome, mRNA Vaccines/adverse effects, Respiratory Syncytial Virus Vaccines/adverse effects, Middle Aged",

author = "\{ConquerRSV Study Group\} and Eleanor Wilson and Jaya Goswami and Baqui, \{Abdullah H\} and Doreski, \{Pablo A\} and Gonzalo Perez-Marc and Khalequ Zaman and Jorge Monroy and Duncan, \{Christopher J A\} and Mugen Ujiie and Mika R{\"a}met and Lina P{\'e}rez-Breva and Falsey, \{Ann R\} and Walsh, \{Edward E\} and Rakesh Dhar and Lauren Wilson and Jiejun Du and Parinaz Ghaswalla and Archana Kapoor and Lan Lan and Shraddha Mehta and Runa Mithani and Panozzo, \{Catherine A\} and Simorellis, \{Alana K\} and Kuter, \{Barbara J\} and Florian Sch{\"o}del and Wenmei Huang and Caroline Reuter and Karen Slobod and Stoszek, \{Sonia K\} and Shaw, \{Christine A\} and Miller, \{Jacqueline M\} and Rituparna Das and Chen, \{Grace L\}",

note = "Copyright {\textcopyright} 2023 Massachusetts Medical Society.",

year = "2023",

month = dec,

day = "13",

doi = "10.1056/NEJMoa2307079",

language = "English",

volume = "389",

pages = "2233--2244",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "24",

}

ConquerRSV Study Group, Wilson, E, Goswami, J, Baqui, AH, Doreski, PA, Perez-Marc, G, Zaman, K, Monroy, J, Duncan, CJA, Ujiie, M, Rämet, M, Pérez-Breva, L, Falsey, AR, Walsh, EE, Dhar, R, Wilson, L, Du, J, Ghaswalla, P, Kapoor, A, Lan, L, Mehta, S, Mithani, R, Panozzo, CA, Simorellis, AK, Kuter, BJ, Schödel, F, Huang, W, Reuter, C, Slobod, K, Stoszek, SK, Shaw, CA, Miller, JM, Das, R & Chen, GL 2023, 'Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults', The New England Journal of Medicine, vol. 389, no. 24, pp. 2233-2244. https://doi.org/10.1056/NEJMoa2307079

TY - JOUR

T1 - Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

AU - ConquerRSV Study Group

AU - Wilson, Eleanor

AU - Goswami, Jaya

AU - Baqui, Abdullah H

AU - Doreski, Pablo A

AU - Perez-Marc, Gonzalo

AU - Zaman, Khalequ

AU - Monroy, Jorge

AU - Duncan, Christopher J A

AU - Ujiie, Mugen

AU - Rämet, Mika

AU - Pérez-Breva, Lina

AU - Falsey, Ann R

AU - Walsh, Edward E

AU - Dhar, Rakesh

AU - Wilson, Lauren

AU - Du, Jiejun

AU - Ghaswalla, Parinaz

AU - Kapoor, Archana

AU - Lan, Lan

AU - Mehta, Shraddha

AU - Mithani, Runa

AU - Panozzo, Catherine A

AU - Simorellis, Alana K

AU - Kuter, Barbara J

AU - Schödel, Florian

AU - Huang, Wenmei

AU - Reuter, Caroline

AU - Slobod, Karen

AU - Stoszek, Sonia K

AU - Shaw, Christine A

AU - Miller, Jacqueline M

AU - Das, Rituparna

AU - Chen, Grace L

PY - 2023/12/13

Y1 - 2023/12/13

N2 - BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

AB - BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

KW - Aged

KW - Humans

KW - Antibodies, Viral

KW - Double-Blind Method

KW - Respiratory Syncytial Virus Infections/epidemiology

KW - Respiratory Syncytial Virus, Human/genetics

KW - Respiratory Tract Diseases/diagnosis

KW - Treatment Outcome

KW - mRNA Vaccines/adverse effects

KW - Respiratory Syncytial Virus Vaccines/adverse effects

KW - Middle Aged

U2 - 10.1056/NEJMoa2307079

DO - 10.1056/NEJMoa2307079

M3 - Article

C2 - 38091530

SN - 0028-4793

VL - 389

SP - 2233

EP - 2244

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 24

ER -

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

Abstract

Keywords

Publication forum classification

UN SDGs

Access to Document

Fingerprint

Cite this