‘Good progress’ being made in RSV prevention research
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After decades of inactivity following a deadly vaccine failure in the 1960s, “there’s been good progress” lately in research to prevent respiratory syncytial virus, according to a speaker at the Infectious Diseases in Children Symposium.
Mary T. Caserta, MD, a professor of pediatrics at the University of Rochester Medical Center, provided an update on several RSV investigational products and vaccines in development for infants and pregnant mothers during a virtual presentation.
Caserta noted that a randomized controlled trial of the investigational monoclonal nirsevimab for protection against RSV-associated lower respiratory tract infection in healthy preterm infants born after 29 weeks’ gestation showed 24% less medically attended lower respiratory tract infection from any cause and a 42% decreased rate of hospitalization from any respiratory cause among participants who received a single injection of nirsevimab compared with the placebo group.
There was a 70% lower incidence of medically attended RSV-associated lower respiratory tract infection in the nirsevimab group, and a 78% lower incidence of hospitalization from RSV-associated lower respiratory tract infection.
Caserta said the decreased risk was sustained for the entire 150-day period after administration of the dose, and that nirsevimab protected against both RSV A and B subtypes, although there were two RSV B isolates obtained from nirsevimab recipients who had decreased susceptibility to the product.
Caserta also summarized results from a phase 3 randomized controlled trial of the human monoclonal antibody suptavumab, which she referred to as a “cautionary tale.”
Published in Clinical Infectious Diseases, the trial found that suptavumab did not decrease medically attended RSV infection, and that there were no significant differences between primary endpoint rates in the treatment or placebo groups.
“When the data were broken down by RSV subtypes, it became clear suptavumab did protect against medically attended lower respiratory tract infection due to RSV A, but there was no protection due to RSV B,” Caserta said.
When sequencing the RSV isolates, the study authors reported two new amino acid changes in the suptavumab binding site in all of the RSV B isolates.
“This change led to substantially decreased binding of the antibody to the viral isolates,” she said. “One hundred percent of the RSV B isolates acquire these two mutations, and it shows how ongoing viral evolution could subvert products directed in a single neutralizing site. Despite this failure, the development of new monoclonal antibody products continues.”
Caserta mentioned RB1, another monoclonal antibody, which was modified and is now referred to as MK-1654. Currently in clinical trials, MK-1654 showed “excellent” neutralizing capability against both RSV A and B in in vitro, Caserta said.
“MK-1654 looks very promising in preclinical studies,” she said.
Caserta noted that some RSV vaccine types, including live attenuated vaccines, are specifically aimed at RSV-naive infants, whereas subunit vaccines are planned for pregnant women.
According to her presentation, a large phase 3 trial of a recombinant RSV F protein nanoparticle vaccine for healthy pregnant women in their third trimester was aimed at protecting newborns from medically significant RSV-associated lower respiratory tract infections for the first 90 days of life.
“Unfortunately, the vaccine efficacy did not meet the primary endpoint,” she reported.
Caserta summarized findings from the trials of seven different live viral vaccines for infants, some that showed promise and some that did not.
References:
Griffin MP, et al. N Engl J Med. 2020:doi.10.1056/NEJMoa1913556.
NIH. Safety, tolerability, and pharmacokinetics of MK-1654 in infants (MK-1654-002). Accessed Nov. 21, 2020.
Simões EAF, et al. Clin Infect Dis. 2020:doi.10.1093/cid/ciaa951.
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Caserta MT. RSV vaccines and antivirals. Presented at: Infectious Diseases in Children Symposium; Nov. 21-22, 2020; virtual.
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