Investigational Vaccine Meets RSV Inoculation Challenge

An investigational vaccine demonstrated protection against respiratory syncytial virus (RSV) infection in a proof-of-concept, human infection model with healthy, young adult participants challenged with intranasal inoculation of the active virus.

"The challenge model was developed to mimic natural infection and to assess the effectiveness of RSV vaccines safely and reproducibly," explained Beate Schmoele-Thomas, MD, Vaccine Research and Development, Pfizer Pharma, Berlin, Germany, and colleagues.

This phase 2a exploratory trial follows assessments of vaccine safety and dosage in adults without the live virus inoculation; and supports proceeding to a planned phase 3, field efficacy study involving 45,000 adults 60 years of age or older who, along with young children, are at heightened risk for serious RSV illness.

The intranasal innoculation comprises 4.5 log 10 plaque-forming units of an RSV A Memphis 37b preparation, which Schmoele-Thomas and colleagues indicate, "has been well characterized in a human challenge model."

The intramuscularly administered vaccine provides a total dose of 120μg of RSVpreF(prefusion F) from equal parts subgroup A Ontario and subgroup B Buenos Aires strains. The preF glycoprotein, a component of the virus envelope prior to entering a host cell, is a target of virus neutralizing antibodies and the key vaccine antigen.

The investigators randomized 70 participants on a 1:1 basis to receive either the RSVpreF vaccine or placebo injection. Approximately 28 days after receiving the injection, 62 of the participants were inoculated with the live virus—except for 2 participants—and completed a 12 day period of quarantine, with a follow-up visit 28 days after the inoculation.

Participants receiving the inoculation rated their symptoms on a 13-item score card up to 3 times a day, from days -12 to 12. The symptoms were categorized as upper or lower respiratory tract and systemic; and ranked for severity on a scale of 0 to 3 with higher scores corresponding to greater severity. Shortness of breath and wheezing at rest were assigned a score of 4.

In addition, the number of tissues used by the participants, as well as the weight of mucus were recorded every 24 hours. Viral RNA was obtained from nasal wash samples, which were collected on day -1 relative to the challenge, twice daily on days 2 to 11, and once on day 12 after the challenge. RSV infection was confirmed by PCR testing of viral presence on at least 2 consecutive days and the presence of at least one clinical symptom of any grade from 2 categories or at least one grade 2 symptom from any category.

The investigators reported an overall vaccine efficacy of 86.7% against symptomatic RSV infection. The efficacy against RSV infection, regardless of the presence, absence, or severity of symptoms, was 75% (95 CI 38.4-90.6) with PCR results on at least 2 consecutive days, and 100% (27.8-100.0) with any one quantifiable culture-confirmed infection. They indicated that no serious adverse events were observed.

In an accompanying editorial, Marie Griffin, MD, MPH, welcomed the favorable results, but noted that the inoculation occurred shortly after vaccination, so the duration of protection is yet unknown. In addition, she pointed out that the relatively short period of follow-up could be insufficient to have identified serious adverse effects.

Griffin also cautioned that these results with young and healthy participants may not coincide with responses in the targeted elderly. "Whether the vaccine will be able to prevent lower respiratory tract disease in persons at higher risk for RSV-associated serious illness has yet to be determined," she indicated.