A phase 1a, first-in-human, randomized study of a respiratory syncytial virus F protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant.
Respiratory syncytial virus (RSV) causes significant illness in older adults resulting in substantial health and economic impact. A successful vaccine would reduce morbidity in this growing segment of the population.



In this double-blind phase 1 study, subjects 60 years of age and older were enrolled by cohort and randomized to receive vaccines containing escalating doses (20, 50, or 80μg) of soluble RSV fusion protein (sF) alone or adjuvanted with 2.5μg of glucopyranosyl lipid A, a toll-like receptor-4 agonist, in 2% stable emulsion (GLA-SE). Each cohort included 20 vaccine and 4 placebo recipients. Immune responses were evaluated using assays for RSV microneutralizing, anti-F IgG, and palivizumab competitive antibodies and for F-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) responses.



The inclusion of adjuvant increased local reactogenicity, with the majority of subjects who received sF and adjuvant reporting low-grade injection site pain or tenderness. At all doses, the safety profile was acceptable for further development. Immune responses were antigen dose-dependent, and the inclusion of adjuvant increased both humoral and cellular immune responses, with responses statistically higher than for placebo recipients in all 4 assays. At the highest dosage level with adjuvant, half of the subjects had a ≥3-fold rise from day 0 in RSV neutralizing antibody titers, and all had a ≥3-fold rise in antibody levels by anti-F IgG and palivizumab competitive antibody assays on day 29. For the day 8 IFNγ ELISPOT assay, 74% of subjects in the highest dosing cohort had a ≥3-fold rise from baseline.



The safety and immunogenicity results from this study support inclusion of the GLA-SE adjuvant in this RSV vaccine for older adults and also support assessment of the efficacy of the vaccine in a larger clinical trial. Clinicaltrials.gov NCT02115815.
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States. Electronic address: FalloonJ@MedImmune.com.
Judith
J
Falloon
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States.
Fei
F
Ji
Compass Research, 100 West Gore St. Suite 202, Orlando, FL 32806, United States.
Craig
C
Curtis
Optimal Research, Optimal Sites, 14808 Physicians Lane, Suite 211, Rockville, MD 20850, United States.
Stephan
S
Bart
Miami Research Associates, 6141 Sunset Dr., South Miami, FL 33143, United States.
Eric
E
Sheldon
Miami Research Associates, 6141 Sunset Dr., South Miami, FL 33143, United States.
Diane
D
Krieger
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States.
Filip
F
Dubovsky
MedImmune, 319 N Bernardo Ave., Mountain View, CA 94043, United States.
Stacie
S
Lambert
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States.
Therese
T
Takas
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States.
Tonya
T
Villafana
MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, United States.
Mark T
MT
Esser
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D004655:Emulsions; D005260:Female; D005960:Glucosides / Q000008:administration & dosage; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008050:Lipid A / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000627:therapeutic use*; D018113:Respiratory Syncytial Virus, Human; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D014760:Viral Fusion Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004655:Emulsions; C526850:F protein, human respiratory syncytial virus; D005960:Glucosides; D007074:Immunoglobulin G; D008050:Lipid A; D022261:Respiratory Syncytial Virus Vaccines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014760:Viral Fusion Proteins; C000608161:glucopyranosyl lipid-A
Adjuvant; Adult; Cell-mediated immunity; Respiratory syncytial virus; Vaccine