A trial examining the effect of an RSV vaccine on pregnant women found it reduced – by 82% – the risk of severe lower respiratory tract infections in newborns, according to Wits vaccinologist Professor Shabir Madhi, who led the research.
Respiratory syncytial virus (RSV) is a dangerous early childhood viral infection, but results of the vaccine study signal a significant change to this landscape.
The research was published in the New England Journal of Medicine.
RSV is the most common cause of acute lower respiratory infection – or pneumonia – in infants. Globally, it was responsible for more than 100 000 deaths (with a lower bound of 84 000 deaths and an upper bound of 126 000 deaths) of children under five in 2019.
Of these, 45% were under six-months-old, and nearly all deaths were in lower income countries (half in Africa alone), reports GroundUp.
In an article in Spotlight in June 2022, Professor Cheryl Cohen, head of the Centre for Respiratory Diseases and Meningitis at the National Institute for Communicable Diseases (NICD), said that, pre-Covid, RSV led to 44 615 hospitalisations and 490 deaths in children under five each year in South Africa.
South Africa is currently experiencing an RSV epidemic, with 301 cases detected this year, reports the NICD.
RSV causes cold-like symptoms, but can lead to severe symptoms like pneumonia. At present, there is no licensed RSV vaccine, though the virus was first identified in the 1960s.
The study was a phase three, double-blind trial, conducted in 18 countries, led by Beate Kampmann, professor of Paediatric Infection and Immunity at the London School of Hygiene and Tropical Medicine, Madhi, who is dean of the Faculty of Health Sciences and professor of Vaccinology at the University of the Witwatersrand, and Iona Munjal, director of Clinical Research & Development at Pfizer. It builds on earlier work by Madhi and others.
Women who were between 24 and 36 weeks pregnant were given an injection of a protein–based vaccine (RSVpreF) and a placebo. Pregnant women can passively transfer their immunity to viruses and diseases to their foetuses in utero.
They were then monitored to see if they suffered a severe RSV-associated lower respiratory tract illness that required medical attention, and if their newborns required medical attention for RSV-associated lower respiratory tract illness up to six months after birth.
A total of 7 358 women participated across the two trial groups, and 7 128 babies were monitored: no safety concerns were identified over the course of the trial.
In November last year, Pfizer announced that it planned to submit a licence application to the US Food and Drug Administration (FDA) after trials showed that the vaccine was highly effective at reducing severe RSV cases in the first 90 days of an infant’s life.
In a Twitter thread announcing the results, Madhi said that the next challenge would be to ensure the vaccine was licensed across lower income countries, where most infant RSV deaths occur. He said there was a “moral responsibility on pharma to licence (the RSV) vaccine in LMIC (Lower and Middle Income Countries) at (an) affordable price”.
Governments in poorer countries “need to act to protect children in their counties by funding and deploying the vaccine timeously”, he said.
Madhi added that coincidentally in the same issue of the New England Journal of Medicine, a medicine called nirsevimab was found to protect infants against RSV-associated hospitalisation and severe lower respiratory tract infections. Madhi and his team at Wits also participated in this trial.
“This medicine is administered as a single dose at the onset of RSV season,” Madhi explained. “The two approaches (the vaccine and nirsevimab) will be complementary.”
Study details
Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants
Beate Kampmann, Shabir A. Madhi, Iona Munjal, Eric Simões, Barbara Pahud, Conrado Llapur, Jeffrey Baker, Gonzalo Pérez Marc, David Radley, Emma Shittu, Julia Glanternik, Hasra Snaggs, et al., for the MATISSE Study Group*
Published in the New England Journal of Medicine on 5 April 2023
Abstract
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.
NEJM article – Nirsevimab for Prevention of RSV in Term and Late-Preterm Infants (Open access)
See more from MedicalBrief archives:
UK approves one-shot RSV vaccine for babies
Respiratory virus killing 100,000 children a year – systemic analysis
Pfizer to apply for approval of first maternal RSV vaccine