A Randomized, Controlled, Observer-Blinded Phase 1 Study of the Safety and Immunogenicity of a Respiratory Syncytial Virus Vaccine With or Without Alum Adjuvant.
BACKGROUND
Respiratory syncytial virus (RSV) is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost preexisting immune responses, providing passive protection to newborns through placental transfer of anti-RSV antibody.


METHODS
In this first-in-humans clinical trial of a purified recombinant RSV protein F vaccine engineered to preferentially maintain prefusion conformation (RSV-PreF), 128 healthy men 18-44 years old were randomized to one dose of a RSV-PreF vaccine containing 10, 30, or 60 µg of RSV-PreF antigen, with or without alum adjuvant, or control, and followed for one year for safety and immunogenicity outcomes.


RESULTS
Injection site pain was the most common adverse event, reported by up to 81.3% of participants. The highest RSV neutralizing antibody responses were in the 30 µg RSV-PreF/alum, 60 µg RSV-PreF/alum, and 60 µg RSV-PreF/nonadjuvant groups. Responses were evident on day 7, and 30 days after vaccination these participants had RSV-A neutralizing antibody titers of ≥1:512, and >70% had titers of 1:1024, with titers increasing by 3.2-4.9 fold. Responses remained high on day 60 but waned on days 180 and 360.


CONCLUSIONS
The RSV-PreF vaccine elicited rapid RSV neutralizing antibody responses in healthy young men, with an acceptable adverse event profile.
Canadian Center for Vaccinology, IWK Health Centre-Nova Scotia Health Authority-Dalhousie University, Halifax.
Joanne M
JM
Langley
Aggarwal and Associates Limited, Brampton.
Naresh
N
Aggarwal
Manna Research, Toronto, Canada.
Azhar
A
Toma
Canadian Center for Vaccinology, IWK Health Centre-Nova Scotia Health Authority-Dalhousie University, Halifax.
Scott A
SA
Halperin
Canadian Center for Vaccinology, IWK Health Centre-Nova Scotia Health Authority-Dalhousie University, Halifax.
Shelly A
SA
McNeil
Vaccine Discovery and Development, GSK Vaccines, Rixensart, Belgium.
Laurence
L
Fissette
Vaccine Discovery and Development, GSK Vaccines, Rixensart, Belgium.
Walthere
W
Dewé
Vaccine Discovery and Development, GSK Vaccines, Rixensart, Belgium.
Maarten
M
Leyssen
Vaccine Discovery and Development, GSK Vaccines, Rixensart, Belgium.
Jean-François
JF
Toussaint
Vaccine Discovery and Development, GSK Vaccines, Rixensart, Belgium.
Ilse
I
Dieussaert
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000534:Alum Compounds; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D055815:Young Adult
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; C041524:aluminum sulfate
maternal immunization; respiratory syncytial virus; vaccine; vaccine safety and immunogenicity
Pediatr Infect Dis J. 1998 Feb;17(2):110-5
9493805
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3089-94
22323598
J Infect Dis. 2016 Feb 1;213(3):411-22
26259809
Vaccine. 2003 Jul 28;21(24):3479-82
12850364
Vaccine. 2015 Nov 25;33(47):6372-3
26263199
J Infect Dis. 2003 Dec 1;188(11):1764-7
14639549
Pediatrics. 1998 Sep;102(3):531-7
9724660
J Allergy Clin Immunol. 2009 Feb;123(2):398-403
19101023
Curr Opin Immunol. 2015 Aug;35:30-8
26070108
Vaccine. 2003 Jul 28;21(24):3465-7
12850361
Curr Top Microbiol Immunol. 2013;372:83-104
24362685
Clin Infect Dis. 2012 May;54(10):1427-36
22495079
Pediatr Infect Dis J. 2008 Mar;27(3):207-12
18277934
Science. 2013 Nov 1;342(6158):592-8
24179220
Lancet. 2010 May 1;375(9725):1545-55
20399493
Pediatrics. 2014 Mar;133(3):e674-88
24567014