Safety and immunogenicity of a respiratory syncytial virus fusion glycoprotein F subunit vaccine in healthy adults: Results of a phase 1, randomized, observer-blind, controlled, dosage-escalation study

• Published in: Vaccine 2019-05, Vol.37 (20), p.2694-2703
• Main Authors: Leroux-Roels, Geert, De Boever, Fien, Maes, Cathy, Nguyen, Thi Lien-Anh, Baker, Sherryl, Gonzalez Lopez, Antonio
• Format: Article
• Language: English
• Subjects: Adjuvant; Adults; Aluminum; Aluminum hydroxide; Antibodies; Binding; Confidence intervals; Disease; Dosage; Enrollments; F protein; Formulations; Glycoprotein; Glycoproteins; Immune response; Immunization; Immunogenicity; Immunoglobulins; Infants; Infections; Men; Pregnancy; Proteins; Randomization; Respiratory syncytial virus; Respiratory tract; Respiratory tract diseases; Safety; Subunit vaccine; Vaccination; Vaccines; Viruses; Womens health
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.04.011

•A RSV F subunit vaccine was developed to protect infants via maternal immunization.•Different formulations of this vaccine in men and non-pregnant women were evaluated.•All formulations of the RSV subunit F vaccine were well-tolerated.•A single dose of this vaccine boosted preexisting neutralizing antibody titers.•All formulations also induced non-neutralizing antibodies to RSV F protein. Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in infants. An investigational vaccine using an engineered recombinant RSV fusion glycoprotein in its post-fusion conformation (RSV F subunit vaccine) has been developed to protect young infants via maternal immunization. This first-in-human, phase I, observer-blind study (NCT02298179) evaluated the safety and immunogenicity of different dosages and formulations of RSV F subunit vaccine in healthy non-pregnant women and men aged 18–45 years. Participants were enrolled (1:1:1) in a stepwise dosage-escalation manner into three cohorts to receive RSV F subunit vaccine containing 45 µg, 90 µg and 135 μg of RSV F glycoprotein. Within each cohort, participants were randomized (1:1:1:1) to receive two doses of RSV F subunit vaccine with (aluminum hydroxide or MF59) or without adjuvant, or placebo, ≥28 days apart. Safety (until day 365 post-dose 2), anti-RSV neutralizing antibodies (NAbs) and serum total binding antibodies to RSV F protein (until day 181 post-dose 1) were evaluated. All formulations were well-tolerated. No vaccine-related serious adverse events were reported. All participants were seropositive for anti-RSV NAbs at baseline, with geometric mean titers (GMTs) ranging from 184 (95% confidence interval [CI]: 127–266) to 380 (95% CI: 272–531). At 28 days post-dose 1, anti-RSV NAb GMTs in vaccine recipients ranged from 893 (95% CI: 702–1,136) to 1,602 (95% CI: 1,243–2,064). No booster effect was observed, but immune responses were maintained above pre-vaccination levels for six months post-dose 1. Ratios of RSV F total binding antibodies fold changes to NAb fold changes ranged from 2.79 to 4.12 at 28 days post-dose 1. The impact of the adjuvant was limited. A single dose of each formulation of RSV subunit F vaccine was well-tolerated and enhanced preexisting NAb titers through six months of follow-up.