A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults

Abstract

Background: Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years.

Methods: Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.

Results: All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.

Conclusions: RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.

Keywords: RSV; prefusion F subunit; respiratory syncytial virus; vaccine.

Conflict of interest statement

Potential conflicts of interest . J. B., A. J., Q. J., K. S., D. C., M. M., J. L., A. G., K. J., W. G., P. D., and B. S.-T. are employees of Pfizer Inc and may hold Pfizer Inc stock or stock options. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.

Participant disposition in the (A) primary cohort and (B) month 0,2 cohort. Abbreviations: AE, adverse event; PBMC, peripheral blood mononuclear cell; RSVpreF 60, 120, and 240, stabilized respiratory syncytial virus prefusion F subunit vaccine (dose levels 60, 120, and 240 µg, respectively).

Figure 2.

Percentages of participants reporting local reactions within 14 days after vaccination in the (A) primary cohort and (B) month 0,2 cohort. Error bars are 95% confidence intervals. Abbreviations: A, Al(OH)3; CpG/A, CpG/Al(OH)3; F 60, 120, and 240, stabilized respiratory syncytial virus prefusion F subunit vaccine (dose levels 60, 120, and 240 µg, respectively).

Figure 3.

Percentages of participants reporting systemic reactions within 14 days after vaccination in the (A) primary cohort and (B) month 0,2 cohort. aMild, moderate, severe, and grade 4 fever defined as temperatures of 38.0–38.4°C, 38.5–38.9°C, 39.0–40.0°C, and >40.0°C, respectively. There were no grade 4 reactions or events. No cases of vomiting were reported. Error bars are 95% confidence intervals. Abbreviations: A, Al(OH)3; CpG/A, CpG/Al(OH)3; F 60, 120, and 240, stabilized respiratory syncytial virus prefusion F subunit vaccine (dose level 60, 120, and 240 µg, respectively).

Figure 4.

RSV A and RSV B neutralizing GMTs at month 1 (A and C) and through month 12 (B and D) in the primary cohort (A and B) and month 0,2 cohort (C and D). Error bars are 95% confidence intervals. Abbreviations: A, Al(OH)3; CI, confidence interval; CpG/A, CpG/Al(OH)3; F 60, 120, and 240, stabilized respiratory syncytial virus prefusion F subunit vaccine (dose levels 60, 120, and 240 µg, respectively); GMFR, geometric mean fold rise; GMT, geometric mean titer; RSV, respiratory syncytial virus.