Pfizer’s Investigational Maternal RSV Vaccine Reduces Illness in Newborns

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Respiratory syncytial virus (RSV) was first identified in the 1950s and has caused a high burden of disease in the years since, especially in highly vulnerable infants and older adults. However, there is still no vaccine approved to reduce the burden of RSV.

Recently, several candidates have advanced in the race to become the world’s first authorized RSV vaccine. In a 2-day meeting, the US Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended approving investigational vaccine candidates from both Pfizer and GSK for individuals 60 years and older.

A new study, however, published tonight in the New England Journal of Medicine, examined Pfizer’s RSV vaccine candidate in a new population: expecting mothers. The investigators sought to determine whether vaccination during pregnancy could reduce the burden of RSV-associated lower respiratory tract illness in newborns and infants.

The phase 3, double-blind, randomized, placebo-controlled MATISSE (Maternal Immunization Study for Safety and Efficacy) trial was conducted in 18 countries over 4 RSV seasons. Study author and investigator Iona M. Munjal, MD, director of clinical research and development at Pfizer, told Contagion that the fatality of RSV infection varies from nation to nation. “Outside of the US, we have 17 other countries… we thought it was equally important to gain data in those countries.”

The study objective was to assess the safety and efficacy of maternal vaccination with Pfizer’s RSV prefusion F protein−based vaccine (RSVpreF). The investigators followed infants for 1-2 years to determine whether RSVpreF protected against medically attended RSV-associated lower respiratory tract illness.

Eligible trial participants were healthy women, aged 49 years or younger, at 24-36 weeks’ gestation on the day of planned RSVpreF injection. Included mothers had an uncomplicated, singleton pregnancy and no known increased risk of pregnancy complications. The women were randomly assigned 1:1 to receive a single intramuscular injection of either 120 μg of RSVpreF vaccine (60 μg each of RSV A and RSV B antigens) or placebo.

A total of 3682 maternal participants received the investigational RSVpreF vaccine and 3676 received placebo, and the investigators subsequently evaluated, respectively, 3570 and 3558 infants.

“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,” the study authors wrote. “Secondary end points included medically attended RSV-associated lower respiratory tract illness, RSV-associated hospitalization, and medically attended lower respiratory tract illness of any cause, all occurring within 360 days after birth.”

The investigators determined that the successful criterion for vaccine efficacy was met. Medically attended severe lower RSV-associated 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, for a vaccine efficacy of 81.8%.

“I'm a pediatrician,” said Munjal, “if I could prevent half of the babies coming into the hospital, I would…82% [efficacy] for me is a really, really amazing achievement for the vaccine. And we're very excited.”

At 180 days after birth, there were 19 cases of medically attended severe lower RSV-associated lower respiratory tract illness in the RSVpreF infants and 62 cases in the placebo cohort.

The secondary endpoint of non-severe medically attended RSV-associated lower respiratory tract illness did not meet the criterion for statistical success, with 24 cases occurring in the RSVpreF infants and 56 cases in the placebo infants at 90 days after birth.

The study authors noted that there were no safety signals detected in maternal participants or in infants and toddlers up to 24 months of age, writing, “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% of women and 34.5% of infants).

Overall, the investigators concluded that Pfizer’s RSVpreF vaccine, administered during pregnancy, was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, with no safety concerns.

“Since the 1960s, you say, ‘Oh I know your baby has RSV, and there’s nothing I can do,’” explained Munjal. She said this investigational maternal RSV truly represents “That really, really impactful, patient-by-patient experience…That’s the joy in this vaccine, you can finally say, ‘I have something to offer.’”