MIRNA – Maternal Immunisation Readiness Network in Africa & Asia
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Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial

Objectives To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF). Methods  MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants […]

Original researchMaternal ImmunisationRSVVaccination2025DOI: https://doi.org/10.1097/aog.0000000000005816
Abstract

The final analysis of the phase 3 MATISSE trial randomized 7,420 healthy pregnant participants (aged 49 or younger, at 24–36 weeks' gestation) to a single dose of the bivalent RSV prefusion F vaccine (RSVpreF, 120 µg) or placebo, resulting in 7,307 births. Vaccine efficacy against severe RSV-associated medically attended lower respiratory tract illness in infants was 82.4% within 90 days and 70.0% within 180 days of birth. The vaccine produced strong immune responses in mothers and efficient antibody transfer to newborns across subgroups, and no new safety concerns emerged. These results confirm the primary analysis: maternal RSVpreF vaccination is safe and protects infants against RSV lower respiratory tract illness through 6 months of age.

Objectives

To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF).

Methods

 MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns.

Results

In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy, defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5–93.9) and 70.0% (95% CI, 50.6–82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified.

Conclusion

This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns.

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Final article information

Final publication metadata, authorship, persistent identifier, reference list and downloadable research files.

Authorship

Authors and affiliations

Eric A. F. Simões, Barbara A. Pahud, Shabir A. Madhi, Beate Kampmann, Emma Shittu, David Radley, Conrado Llapur, Jeffrey Baker, Gonzalo Pérez Marc, Shaun L. Barnabas, Merlin Fausett, Tyler Adam, Nicole Perreras, Marlies A. Van Houten, Anu Kantele, Li-Min Huang, Louis J. Bont, Takeo Otsuki, Sergio L. Vargas, Joanna Gullam, Bruce Tapiero, Renato T. Stein, Fernando P. Polack, Heather J. Zar, Nina B. Staerke, María Duron Padilla, Peter C. Richmond, Uzma N. Sarwar, James Baber, Kenneth Koury, Maria Maddalena Lino, Elena V. Kalinina, Weiqiang Li, David Cooper, Annaliesa S. Anderson, Kena A. Swanson, Alejandra Gurtman, Iona MunjalChildren's Hospital Colorado, Aurora, Colorado; Vaccine Research and Development, Pfizer Inc, Pearl River, New York; the South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit and Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, and Famcru, Department of Paediatrics and Child Health, University of Stellenbosch, and the Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; Vaccines and Immunity Team, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, the Gambia; Institute for International Health Charité, Universitätsmedizin, Berlin, Germany; Vaccine Research and Development, Pfizer Ltd, Marlow, United Kingdom; Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes, San Miguel de Tucumán, and iTrials-Hospital Militar Central and iTrials, Buenos Aires, Argentina; Clinical Research Prime, Idaho Falls, Idaho; Boeson Research, Missoula, Montana; Meridian Clinical Research, Hastings, Nebraska; Asian Hospital and Medical Center, Manila, the Philippines; Department of Pediatrics, Spaarne Gasthuis, Haarlem and Hoofddorp, the Department of Pediatrics, Department of Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, and the ReSViNET Foundation, Zeist, the Netherlands; Meilahti Vaccine Research Center MeVac, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; National Taiwan University Hospital, Taipei, Taiwan; the Department of Obstetrics and Gynecology, Sendai City Hospital, Sendai, Japan; Institute of Biomedical Sciences, University of Chile School of Medicine, Santiago, Chile; University of Otago and New Zealand Clinical Research, Christchurch, New Zealand; CHU Sainte-Justine, Montreal, Quebec, Canada; Hospital Moinhos de Vento and Pontifícia Universidade Católica RGS, Porto Alegre, Brazil; the Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; Arké SMO S.A. de C.V., Mexico City, Mexico; 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, Western Australia, and Vaccine Clinical Research, Pfizer Inc, Sydney, Australia; and Worldwide Safety, Pfizer Srl, Milan, Italy.

Corresponding author: Iona Munjal, MD, Vaccine Research and Development, Pfizer Inc, Pearl River, NY; Iona.Munjal@pfizer.com.

DOI

Digital Object Identifier

https://doi.org/10.1097/aog.0000000000005816
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Final references

References

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