A bivalent protein-based respiratory syncytial virus (RSV) vaccine given to pregnant women is safe and elicits neutralizing antibodies which transfer to their offspring, according to a planned interim analysis of a Phase IIb trial.
In the industry-supported study of the Pfizer bivalent RSV prefusion F protein-based vaccine candidate (RSFpreF vaccine), researchers immunised women in the late second or third trimester of pregnancy to examine the vaccine’s safety and immunogenicity in them and their offspring.
Writing in the New England Journal of Medicine, the study authors said neutralising immunogenic responses occurred in the vaccinated women and their infants, but not in the women who had received a placebo and their infants.
The trial was not designed to formally assess for vaccine efficacy, but in an exploratory post-hoc analysis, researchers found efficacy of 85% and 92% for medically attended and severe medically RSV-associated lower respiratory tract illness in infants, respectively, although given the low case numbers they noted the confidence intervals were wide.
The study included 406 women and 403 infants, with women randomised to one of five groups, receiving either 120 or 240 µg of RSVpreF vaccine with or without aluminium hydroxide or placebo.
Researchers reported the geometric mean ratios of 50% neutralising titres between those of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralising antibodies and from 13.6 to 16.8 among those with RVS B neutralising antibodies.
'Transplacental neutralising antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminium formulations than with aluminium formulations,' the researchers wrote.
'These serologic and initial efficacy data suggest that maternal vaccination with RSV-preF vaccine during pregnancy has the potential to protect infants from RSV infection well into their first six months of life.'
Most post-vaccination reactions were mild to moderate and incidence of adverse events in were similar in the vaccine and placebo groups, they said, and consistent with the background incidences among pregnant women and infants.
A phase III clinical efficacy trial of the vaccine involving infants of women born to women who received 120 µg of RSVpreF vaccine without aluminium hydroxide is underway, the authors said.
A monoclonal antibody, palivizumab, given as several doses over respiratory virus season is approved to prevent serious RSV disease in infants with specific risk factors, the study authors noted, but there are currently no RSV vaccines.
The researchers explained that in the 1960s a different type of RSV vaccine led to vaccinated infants developing more severe disease when they contracted RSV, with the 'subsequent development of vaccines hampered by an inability to balance side effects with immunogenicity'.
Research which determined the prefusion structure of the RSV F protein, the primary target of neutralising antibodies, revitalised the development of RSV vaccines, the study authors noted.
According to the non-profit health organisation PATH, there are now a host of candidate RSV vaccines and monoclonal antibodies in development aimed at preventing disease in children and older adults, with several now reaching Phase III trials. GlaxoSmithKline, for example, is expecting results from a Phase III trial of an RSV candidate vaccine for older adults in the first half of this year, but earlier this year announced it was halting trials of a maternal RSV vaccine.
In April this year, Bavarian Nordic announced the start of a Phase III RSV vaccine trial in older adults, with results expected next year.
Meanwhile in March, AstraZenca and Sanofi reported Phase III trial results showing a single dose of their monoclonal antibody nirsevimab had 74.5% efficacy against medically attended lower respiratory tract infections caused by RSV in healthy infants.