A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.
Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity.



A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months.



Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%).



Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated.
NanoPass Technologies, Israel. Electronic address: yotam@nanopass.com.
Yotam
Y
Levin
NanoPass Technologies, Israel.
Efrat
E
Kochba
Janssen Vaccines AG, Switzerland.
Georgi
G
Shukarev
Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Sarah
S
Rusch
Medical Department, Johnson & Johnson, Horsham, PA, United States.
Guillermo
G
Herrera-Taracena
Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Belgium.
Pierre
P
van Damme
D000276:Adjuvants, Immunologic; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D022721:Vaccines, Virosome
Adjuvant; High-dose; Immunogenicity; Influenza vaccine; Intradermal; Microneedle