An Adjuvanted, Postfusion F Protein-Based Vaccine Did Not Prevent Respiratory Syncytial Virus Illness in Older Adults

Abstract

Background: Respiratory syncytial virus (RSV) is an important cause of illness in older adults. This study assessed efficacy of a vaccine for prevention of RSV-associated acute respiratory illness (ARI), defined by specified symptoms with virologic confirmation.

Methods: This phase 2b study evaluated RSV postfusion F protein (120 µg) with glucopyranosyl lipid adjuvant (5 µg) in 2% stable emulsion. Subjects aged ≥60 years were randomly assigned at a ratio of 1:1 to receive vaccine or placebo (all received inactivated influenza vaccine). Ill subjects recorded symptoms and provided blood and nasal swab samples.

Results: In the per-protocol population (n = 1894), the incidence of RSV-associated ARI occurring ≥14 days after dosing was 1.7% and 1.6% in the vaccine and placebo groups, respectively, for a vaccine efficacy (VE) of -7.1% (90% confidence interval [CI], -106.9%-44.3%). Efficacy was not observed in secondary analyses that included seroresponse to nonvaccine RSV antigens (VE, 8.9%; 90% CI, -28.5%-35.4%) or symptoms combined with seroresponse (VE, 10.0%; 90% CI, -45.4%-44.4%). On day 29, 92.9% of vaccinees had an anti-F immunoglobulin G antibody seroresponse. Overall, 48.5% and 30.9% of RSV vaccine recipients reported local and systemic solicited symptoms, respectively.

Conclusion: The RSV vaccine was immunogenic but did not protect older adults from RSV illness.

Clinical trials registration: NCT02508194.

Keywords: Adjuvant; clinical trial; efficacy; respiratory syncytial virus; subunit; vaccine.

Figure 1.

Disposition of subjects (as treated; 1 subject who was randomly assigned to receive respiratory syncytial virus (RSV) vaccine received placebo in error). IIV, inactivated influenza vaccine; PI, principal investigator. ^aCompleted efficacy follow-up.

Figure 2.

Forest plot of vaccine efficacy (VE) for the first episode of acute respiratory syncytial virus (RSV)–associated respiratory illness (ARI) or by seroresponse in the per protocol (PP) population. Assessment was during the surveillance period, starting 14 days after dosing, unless otherwise noted. A, Efficacy according to RSV-associated ARI definition (first episode of RSV-associated ARI symptoms plus RSV detection in respiratory specimen by polymerase chain reaction analysis). B, Efficacy according to seroresponse definition (ie, RSV-associated ARI symptoms plus seroresponse to nonvaccine antigens). CI, confidence interval; ITT, intention to treat; LRTI, lower respiratory tract illness.

Figure 3.

Anti–respiratory syncytial virus (RSV) fusion protein immunoglobulin G (IgG) antibody results at baseline, day 29, and the end of the RSV infection season. CI, confidence interval.

Figure 4.

Geometric mean respiratory syncytial virus (RSV) microneutralizing (MN) antibody titer (A) and palivizumab-competitive antibody (PCA) values (B) at baseline and on day 29 after dosing in subjects who met the primary end point or were selected to match them (in a 1:6 ratio) or to match the sample size of a group that received the same formulation in a phase 1b study (clinical trials registration: NCT02289820) through random sampling stratified by age and sex and controlled over baseline anti–RSV fusion protein immunoglobulin G levels, region, and comorbidity status. C, Cell-mediated response to RSV, as measured by RSV interferon γ enzyme-linked immunospot assay, in subjects who met the primary end point or who were randomly selected on the basis of sample availability. CI, confidence interval; IC₅₀, inhibitory concentration at 50%; SFC, spot-forming cells.