Safety and Immunogenicity of a Carbohydrate Fatty Acid Monosulphate Ester Adjuvant Combined with a Low-Dose Quadrivalent Split-Virion Inactivated Influenza Vaccine: A Randomised, Observer-Blind, Active-Controlled, First-in-Human, Phase 1 Study
Valentino D’Onofrio,
Sharon Porrez,
Bart Jacobs,
Azhar Alhatemi,
Fien De Boever,
Gwenn Waerlop,
Els Michels,
Francesca Vanni,
Alessandro Manenti,
Geert Leroux-Roels,
Peter Paul Platenburg,
Luuk Hilgers,
Isabel Leroux-Roels
Affiliations
Valentino D’Onofrio
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Sharon Porrez
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Bart Jacobs
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Azhar Alhatemi
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Fien De Boever
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Gwenn Waerlop
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Els Michels
Harmony Clinical Research BV, 9090 Melle, Belgium
Francesca Vanni
VisMederi S.r.l., 53035 Monteriggioni, Italy
Alessandro Manenti
VisMederi S.r.l., 53035 Monteriggioni, Italy
Geert Leroux-Roels
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Peter Paul Platenburg
LiteVax, 4061 BJ Ophemert, The Netherlands
Luuk Hilgers
LiteVax, 4061 BJ Ophemert, The Netherlands
Isabel Leroux-Roels
Center for Vaccinology (CEVAC), Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium
Seasonal influenza vaccine effectiveness is low. Carbohydrate fatty acid monosulphate ester (CMS), a new oil-in-water adjuvant, has proven potency in animal models with suggested capacity for dose-sparing. The objective was to evaluate safety and immunogenicity of CMS when added to a low-dose influenza vaccine (QIV) in humans. In a randomised, double-blind, active-controlled, first-in-human study, sixty participants (18–50 years) received either 0.5 mg CMS or 2 mg CMS with 1/5th dose QIV, or a full dose QIV without CMS. Adverse events (AE) were monitored until 7 days post-vaccination. Haemagglutinin inhibition (HI) titres in serum and CD4+ T cells in PBMCs were determined at day 0, 7, 28, and 180. Mean age was 37.6 (±10.1) years and 42/60 (70.0%) were female. Pain at injection site (42/60, 86.7%) and headache (34/60, 56.7%) were reported most and more frequently in the 2 mg CMS group. HI titres and the frequency of influenza specific CD4+ T cells were equal across strains for the three cohorts on all visits, increased until day 28 and decreased at day 180 to values higher than baseline. CMS was safe in humans. Humoral and cell-mediated immunogenicity was similar across vaccines, even with 1/5th antigen dose. CMS can have beneficial implications in low-resource settings or in a pandemic context.