MIRNA – Maternal Immunisation Readiness Network in Africa & Asia
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Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

Background Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)–associated lower respiratory tract illness in newborns and infants is uncertain. Methods In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks’ gestation to receive a single intramuscular […]

Original researchMaternal ImmunisationRSVVaccination2023DOI: https://doi.org/10.1056/nejmoa2216480
Abstract

At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occured within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 17.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively)

Background

Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)–associated lower respiratory tract illness in newborns and infants is uncertain.

Methods

In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks’ gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein–based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.

Results

At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).

Conclusions

RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.)

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Beate Kampmann, M.D., Ph.D., Shabir A. Madhi, M.B., B.Ch., Ph.D, Iona Munjal, M.D., Eric A.F. Simões, M.D., Barbara A. Pahud, M.D., M.P.H., Conrado Llapur, M.D., Jeffrey Baker, M.D., Gonzalo Pérez Marc, M.D., David Radley, M.S., Emma Shittu, Ph.D., Julia Glanternik, M.D. https://orcid.org/0000-0001-9004-8558, Hasra Snaggs, M.D., James Baber, M.B., Ch.B., M.P.H., Philip Zachariah, M.D., Shaun L. Barnabas, M.B., Ch.B., Ph.D., Merlin Fausett, M.D., Tyler Adam, M.D., Nicole Perreras, M.D., Marlies A. Van Houten, M.D., Ph.D., Anu Kantele, M.D., Ph.D., Li-Min Huang, M.D., Ph.D., Louis J. Bont, M.D., Ph.D., Takeo Otsuki, M.D., Ph.D., Sergio L. Vargas, M.D., Joanna Gullam, M.B., Ch.B., M.D., Bruce Tapiero, M.D., Renato T. Stein, M.D., Fernando P. Polack, M.D., Heather J. Zar, M.B., B.Ch., Ph.D., Nina B. Staerke, M.D., Ph.D., María Duron Padilla, M.D., Peter C. Richmond, M.B., B.S., Kenneth Koury, Ph.D., Katherine Schneider, Ph.D., Elena V. Kalinina, Ph.D., David Cooper, Ph.D., Kathrin U. Jansen, Ph.D., Annaliesa S. Anderson, Ph.D., Kena A. Swanson, Ph.D. https://orcid.org/0000-0002-3389-8414, William C. Gruber, M.D., and Alejandra Gurtman, M.D., for the MATISSE Study Group*From the Medical Research Council Unit the Gambia, London School of Hygiene and Tropical Medicine, Fajara, Gambia (B.K.); the Institute for International Health Charité, Universitätsmedizin, Berlin (B.K.); the South African Medical Research Council (MRC) Vaccines and Infectious Diseases Analytics Research Unit, Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg (S.A.M.), and Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, University of Stellenbosch (S.L.B.), and the Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, South African MRC Unit on Child and Adolescent Health, University of Cape Town (H.J.Z.), Cape Town — all in South Africa; Vaccine Research and Development, Pfizer, Pearl River, NY (I.M., B.A.P., D.R., J. Glanternik, H.S., P.Z., K.K., K.S., E.V.K., D.C., K.U.J., A.S.A., K.A.S., W.C.G., A.G.); Children’s Hospital Colorado, Aurora (E.A.F.S.); Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes, San Miguel de Tucumán (C.L.), and iTrials–Hospital Militar Central (G.P.M., F.P.P.) and iTrials (S.L.V.), Buenos Aires — all in Argentina; Clinical Research Prime, Idaho Falls, ID (J. Baker); Vaccine Research and Development, Pfizer, Hurley, United Kingdom (E.S.); Vaccine Clinical Research, Pfizer, Sydney, NSW (J. Baber), and the University of Western Australia School of Medicine, Vaccine Trials Group, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, and Perth Children’s Hospital, Nedlands, WA (P.C.R.) — all in Australia; Boeson Research, Missoula, MT (M.F.); Meridian Clinical Research, Hastings, NE (T.A.); Asian Hospital and Medical Center, Manila, Philippines (N.P.); the Department of Pediatrics, Spaarne Gasthuis, Haarlem and Hoofddorp (M.A.V.H.), and the Departments of Pediatrics and Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, and Respiratory Syncytial Virus Network Foundation, Zeist (L.J.B.) — all in the Netherlands; Meilahti Vaccine Research Center, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki (A.K.); National Taiwan University Hospital, Taipei (L.-M.H.); the Department of Obstetrics and Gynecology, Sendai City Hospital, Sendai, Japan (T.O.); the Institute of Biomedical Sciences, University of Chile School of Medicine, Santiago, Chile (S.L.V.); University of Otago and New Zealand Clinical Research — both in Christchurch, New Zealand (J. Gullam); Centre Hospitalier Universitaire Sainte-Justine, Montreal (B.T.); Hospital Moinhos de Vento and Pontifícia Universidade Católica do Rio Grande do Sul — both in Porto Alegre, Brazil (R.T.S.); the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark (N.B.S.); and Arké Study Management Organization, Mexico City (M.D.P.).
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https://doi.org/10.1056/nejmoa2216480
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