Investigational RSVpreF Vaccine Shows Efficacy in Infants, Elderly

A single injection of the investigational bivalent respiratory syncytial virus (RSV) perfusion F protein-based (RSVpreF) vaccine was found protective against RSV-related illness in infants and older adults enrolled in two phase III randomized trials, with few significant safety concerns observed.

In the MATISSE study, investigator Beate Kampmann, MD, PhD, of the London School of Hygiene and Tropical Medicine, and colleagues, are examining the vaccine’s efficacy when given to women during pregnancy for preventing medically-significant RSV-related lower respiratory tract illness in newborns.

In the RENOIR study, investigators Edward Walsh, MD, of the University of Rochester Medical Center, Rochester, New York, and colleagues are evaluating the RSVpreF vaccine’s safety and efficacy for preventing RSV-associated lower respiratory illness in older adults (≥60 years).

Interim results from both studies were published online April 5 in The New England Journal of Medicine.

The phase III MATISSE trial enrolled 7,392 pregnant women in 18 countries who received a single 120 μg intramuscular injection of the vaccine or placebo at weeks 24-36 of gestation.

Both trials were conducted during the Covid-19 pandemic, which greatly altered typical RSV seasons during the study.

Interim data from both trials were reported, with additional findings to be published after two RSV seasons in the RENOIR trial and when the infants in the MATISSE trial reached age 12-months and 24-months.

The interim RENOIR analysis (data cutoff date, July 14, 2022) included 44 cases of RSV lower respiratory tract illness in the older adults, which occurred before all participants completed the first RSV season.

Walsh and colleagues noted that there were not enough cases of severe RSV-associated lower respiratory tract illness reported by the time the interim data were analyzed to evaluate efficacy against illness requiring hospitalization, oxygenation, or mechanical ventilation.

Vaccination achieved both primary endpoints for the study, with a 66.7% vaccine efficacy reported against RSV-associated lower respiratory tract illness with two or more symptoms or signs related to illness and 85.7% vaccine efficacy against related illness with three or more signs or symptoms.

RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 older adults in the vaccine group (1.19 cases per 1,000 person-years of observation) and 33 in the placebo group (3.58 cases per 1,000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8-85.8).

"Two cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0-98.7)," the researchers wrote. "RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1,000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1,000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1-77.9)."

The researchers concluded that the RSVpreF vaccine generally had acceptable safety- and side-effect profiles, but a single case of Guillain-Barre syndrome and a single case of Miller-Fisher syndrome were reported at days 7 and 8 after vaccination, respectively.

The interim analysis of the MATISSE trial was conducted when 4-out-of-5 (79%) infants had completed 180 days of follow-up, with 80 evaluable cases of medically attended RSV-associated lower respiratory tract illness reported within 90 days of birth and 174 cases reported within 180 days of birth.

RSVpreF vaccination met a primary endpoint of preventing medically attended severe RSV-associated lower respiratory tract illness in infants, with vaccine efficacy of 81.8% (99.5% CI, 40.6-96.3) within 90 days after birth and 69.4% (97.58% CI, 44.3-84.1) within 180 days after birth.

However, maternal vaccination during pregnancy did not meet the prespecified primary efficacy endpoint for reducing all medically attended RSV-associated lower respiratory tract illness within 90 days of birth.

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, 14.7-79.8).

And there was no evidence that vaccination prevented medically attended lower respiratory tract illness from any cause within 90 days of birth, with vaccine efficacy against all-cause lower respiratory illness just 7.0%.

"In our trial, which was conducted during the Covid-19 pandemic, medically attended RSV-associated lower respiratory tract illness within 180 days after birth constituted only 22% of medically attended lower respiratory tract illness due to any cause in the same period (174 of 794 cases)," Kampmann et al wrote. "In contrast, in pre-pandemic studies of lower respiratory tract illness, RSV was the most common individual pathogen in areas where pneumococcal conjugate vaccines were used, and it was responsible for 50 to 80% of hospitalizations for bronchiolitis and 40% of cases of pneumonia among children younger than 1 year of age."

In an editorial evaluating the interim analyses, Ruth A. Karron, MD, of Johns Hopkins University, Baltimore, wrote that the RENOIR and MATISSE trials "move us closer to prevention of RSV illness in the old and young."

Karron noted that "critical scientific questions about the RSVpreF vaccine remain," including the RSVpreF vaccine’s efficacy against serious disease in older adults, the best strategy for optimizing vaccination during pregnancy, and best use of the vaccine in low-resource settings.

"These two articles and previous articles describe landmark accomplishments in the fight against RSV illness," Karron wrote. "This progress is remarkable, but substantial additional work to guide decision making and implementation is essential. We are only at the beginning of the end."

The Matisse study was funded by Pfizer and multiple investigators are employees of the company. Principal investigator Jeffrey Baker reported payment from Pfizer for screening, enrolling and managing participants in the study. Kampmann reported receiving grants and travel expenses from Pfizer Pharma GMBH. The Renoir study was funded by Pfizer and multiple investigators are employees of the company. Lead investigator Edward Walsh reported receiving consulting and/or other fees from Janssen Pharmaceuticals, Merck, Moderna and Pfizer. Corresponding author Alejandra Gurtman reported being a Pfizer employee. Editorial writer Karron reported receiving grants or personal fees from Pfizer Vaccines, Sanofi Vaccines and the NIH.

Kampmann B, et al "Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants" N Engl J Med 2023; DOI: 10.1056/NEJMoa2216480.

Walsh EE, et al "Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults" N Engl J Med 2023; DOI: 10.1056/NEJMoa2213836.

Karron RA "RSV illness in the young and old—The beginning of the end?" N Engl J Med 2023; DOI: 10.1056/NEJMe2302646.