Safety, reactogenicity and immunogenicity of an intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix (GEM) particles (FluGEM): A randomized, double-blind, controlled, ascending dose study in healthy adults and elderly

• Published in: Vaccine Vol. 42; no. 22; p. 125836
• Main Authors: van der Plas, Johan L., Haijema, Bert-Jan, Leenhouts, Kees, Paul Zoeteweij, J., Burggraaf, Jacobus, Kamerling, Ingrid M.C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 17.09.2024; Elsevier Limited
• Subjects: Adjuvant; Adjuvants; Adverse events; Allergy and Immunology; antibodies; Antigens; Bacteria; Bacteria-like; blood serum; Clinical trials; Coronaviruses; COVID-19; dose response; elderly; Gram-positive bacteria; hemagglutination; Hemagglutination inhibition; Human performance; Human subjects; humans; Immunity (Disease); Immunogenicity; Immunoglobulin A; Influenza; influenza vaccines; Intranasal; Intranasal administration; Medical screening; Mucosa; Mucosal immunity; Netherlands; Nonlinear response; Older people; Peptides; Safety; Seroconversion; Vaccination; Vaccines; Viruses; United States > US; Netherlands; Bacteria-like; Adjuvant; Intranasal; Mucosa; Vaccination; Influenza
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.03.063

•Intranasal vaccination could induce protective mucosal immunity as well as systemic immunity with easy-to-use needle-free administration.•Novel safe adjuvants are needed to help boost immunogenicity for intranasal influenza vaccines.•Intranasal administration of gram-positive enhancer matrix (GEM), a bacterium-like particle derived from Lactococcus lactis, was safe in a first-in-human trial and showed potential as adjuvant in combination with inactivated trivalent influenza vaccine. Intranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry. Immunogenicity of intranasal vaccination can be improved through the use of adjuvants. Bacteria-like particles derived fromLactococcus lactishave the potential to serve as a vaccine adjuvant.This clinical study investigated the safety, reactogenicity and immunogenicity of intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix particles (FluGEM®). This was a first-in-human, randomized, double-blind, controlled, dose-escalation study performed at the Centre for Human Drug Research (CHDR), the Netherlands. Participants aged 18–49 were randomized in a 3:1 ratio to receive FluGem® in ascending doses (two-dose regimens) together with a standard trivalent inactivated influenza vaccine or unadjuvanted TIV only. Primary outcomes were safety and tolerability. Secondary outcomes were serum hemagglutination inhibition (HI) antibody titers and mucosal IgA. The most immunogenic dose was used in an additionalelderly cohort (>65 years). Ninty participants were included. Intranasal FluGem®was safe and well tolerated. The majority of adverse events were mild (97.4 %) with (un)solicited adverse events comparable across all dose levels and control groups. All groups showed geometric mean increases ≥ 2.5-fold. Seroconversion (≥40 % participants) was achieved at both day 21 (single-dose) and 42 (two-dose) for the 1.25 mg dose and on day 42 (two-dose only) for the 2.5 mg dose. Highest geometric mean IgA increases were observed in the 1.25 mg group on day 21. Immunogenicity was less pronounced in elderly. Intranasal vaccination of FluGEM®was safe and tolerable in healthy adult volunteers aged 18–49 years and 65 and older. Highest immunogenicity was observed for 1.25 mg and 2.5 mg doses (compared to 5 mg) suggesting a potential non-linear dose–response relationship.More research is needed to further investigate the capabilities of bacteria-like peptides as adjuvants.