Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and ‘booster’ responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.
We analyzed data from 7 phase 1 trials of live-attenuated RSV vaccines in 6-to-24-month-old children (n=239).
The 5 vaccine regimens that induced neutralizing antibody responses in ≥80% of vaccinees (defined post hoc as ‘more promising’) protected against RSV-associated medically-attended acute respiratory illness (RSV-MAARI) and medically-attended acute lower respiratory illness (RSV-MAALRI), and primed for potent anamnestic responses upon natural exposure to wild-type RSV. Among recipients of ‘more promising’ RSV vaccines, efficacy against RSV-MAARI was 67% (95% CI[24, 85],p=0.008) and against RSV-MAALRI was 88% (95% CI[-9, 99], p=0.04). ≥4-fold increase in RSV serum neutralizing antibody following vaccination was strongly associated with protection against RSV-MAARI (OR=0.26,95% CI [0.09, 0.75], p=0.014]) and RSV-MAALRI; no child with a ≥4-fold increase developed RSV-MAALRI. Rates of RSV-MAARI and RSV-MAALRI in placebo recipients were 21% and 7%, respectively. Given these rates, a study of 540 RSV-naïve children would have 90% power to demonstrate ≥55% efficacy against RSV-MAARI and ≥80% efficacy against RSV-MAALRI; if rates were 10% and 3%, a study of 1300 RSV-naïve children would be needed.
Rapid development of a live-attenuated RSV vaccine could contribute substantially to reducing the global burden of RSV disease.