Vaccine Candidate Effective in Preventing Against RSV, Phase 2a Study Finds

Results from a phase 2a study show that a bivalent prefusion F vaccine was effective against symptomatic respiratory syncytial virus (RSV) infection and viral shedding, with no identified safety concerns.

A single dose of a bivalent prefusion F (RSVpreF) vaccine candidate was shown to be effective in preventing symptomatic respiratory syncytial virus (RSV) infection and limited the duration of viral shedding in healthy adults with no safety concerns. These findings were published in The New England Journal of Medicine.

There is currently no vaccine available for RSV, a common respiratory virus with symptoms that can lead to lower respiratory infections and hospitalizations. However, numerous pharmaceutical companies are conducting research in the RSV vaccine space, including Pfizer, the manufacturer of the RSVpreF candidate examined in the current study. The prefusion F glycoprotein is a major target of virus-neutralizing antibodies and a key antigen in RSV vaccines, the authors noted.

The phase 2a, single-center, randomized, double-blind, exploratory study had 3 phases: screening, injection, and quarantine, with a 6-month safety follow-up. The study involved 70 healthy adults aged 18 to 50 years. To ensure the cohort’s susceptibility to RSV, participants had RSV A–neutralizing titers in the lowest quartile of the population titer distribution in the past 12 months.

Researchers randomly assigned participants in a 1:1 ratio to either receive 120 mcg of RSVpreF vaccine (nonadjuvanted) or placebo. The RSVpreF vaccine contained equal amounts of 2 stabilized prefusion F antigens. The placebo was a lyophile match to the RSVpreF vaccine but without the active ingredients. A single intramuscular injection of the vaccine or placebo was given to each participant.

In the challenge portion of the study, participants were inoculated intranasally with an RSV Memphis 37b challenge virus 28 days after receiving the injection. The date participants were challenged with the RSV virus was noted as day 0. Participants were then quarantined and observed for 12 days, with follow-up visits 28 days after challenge and 6 months after injection.

Thirteen-item symptom scorecards ranked upper respiratory tract symptoms, lower respiratory tract symptoms, and systemic symptoms. Participants completed this scorecard up to 3 times a day from day –2 (2 days before challenge) to day 12.

Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to measure viral RNA in nasal wash samples collected from participants once on day –1, twice daily from days 2 to 11, and once on day 12.

The per-protocol prespecified primary end points were as follows:

  • RSV infection, as confirmed by RT-qPCR, on at least 2 consecutive days with at least 1 clinical symptom of any grade from 2 categories or at least 1 grade 2 symptom from any category.
  • The total symptom score, assessed by the 13-item scorecards, from day 1 to discharge.
  • The area under the curve (AUC) for the viral load in nasal wash samples (measured by RT-qPCR) from day 2 to discharge.

RSVpreF vaccine efficacy for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days was 86.7%. After inoculation with the challenge virus, the percentages of participants with symptomatic infection in the RSVpreF vaccine group and placebo group were 6% and 48%, respectively.

For the RSV viral load, the median AUC measured by RT-qPCR assay was 0.01 in the RSVpreF vaccine group and 96.7 in the placebo group. The geometric mean factor increases in RSV A–neutralizing titers from baseline to 28 days after injection were 20.5 in the vaccine group and 1.1 in the placebo group.

In the vaccine group, more local injection site pain was recorded than in the placebo group. No serious adverse events were recorded in either group.

Limitations of this study include the use of an experimental challenge instead of real-world conditions, the relatively small sample size, and the preselection of participants with low RSV-neutralizing titers. Another limitation is the younger age of participants; the target population for this vaccine is older adults.

Data from this study support a further phase 3 efficacy study to evaluate the RSVpreF vaccine, the researchers concluded.

Reference

Schmoele-Thoma B, Zareba AM, Jiang Q, et al. Vaccine efficacy in adults in a respiratory syncytial virus challenge study. N Engl J Med. 2022;386(25):2377-2386. doi:10.1056/NEJMoa2116154