Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses.
In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18–60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity.
Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated.
World Health Organization. Influenza virus infections in humans. 2014. Available at: http://www.who.int/influenza/human_animal_interface/virology_laboratories_and_vaccines/influenza_virus_infections_humans_feb14.pdf. Accessed 13 Apr 2015.
World Health Organization. Influenza (Seasonal) Fact sheet Number 211 March 2014.
European Commission. Proposal for a Council Recommendation on seasonal influenza vaccination. 2009. Available at: http://ec.europa.eu/health/ph_threats/com/Influenza/docs/seasonflu_rec2009_en.pdf. Accessed 13 April 2015.
Lee K, Seong BL. Current status for influenza control. Biotechnol Bioprocess Eng. 1999;4:157–64. CrossRef
Shtyrya YA, Mochalova LV, Bovin NV. Influenza virus neuraminidase: structure and function. Acta Nat. 2009;1(2):26–32.
World Health Organization. Questions and answers. Vaccine effectiveness estimates for seasonal influenza vaccines. 2015. Available at: http://www.who.int/influenza/vaccines/virus/recommendations/201502_qanda_vaccineeffectiveness.pdf. Accessed 13 April 2015.
ALEA. Release version 15.1. Available at: https://www.tenalea.com/nkiavl/ALEA/Login.aspx.
Salk HM, Haralambieva IH, Ovsyannikova IG, Goergen KM, Poland GA. Granzyme B ELISPOT assay to measure influenza-specific cellular immunity. J Immunol Methods 2013;398-399:44-50.
Pleguezuelos O, Robinson S, Fernandez A, Stoloff GA, Mann A, Gilbert A, et al. A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clin Vaccine Immunol. 2015;22(7):828–35. CrossRefPubMedPubMedCentral
Ascarateil S, Puget A, Koziol M. Safety data of Montanide ISA 51 VG and Montanide ISA 720 VG, two adjuvants dedicated to human therapeutic vaccines. J Immunother Cancer. 2015;3(suppl 2):428. CrossRef
- Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial
Eva van Doorn
Henderik W. Frijlink
- BioMed Central
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