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

Abstract

BackgroundCurrent 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.MethodsIn 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.DiscussionBroadly 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.Trial registrationEudraCT number 2015–001932-38; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).

In silico design of a multi-epitope peptide construct as a potential vaccine candidate for Influenza A based on neuraminidase protein

“…Some of the candidates used in clinical trials show the possibilities in the decreasing Influenza infection (Sebastian and Lambe 2018 ; Sautto et al 2018 ; Nachbagauer and Palese 2019 ). However, vaccine candidates which are currently in use at clinical studies are aimed to elicit an antibody response against more conserved Influenza proteins (Doorn et al 2017a , 2017b ). Furthermore, the limitations of currently in market seasonal Influenza vaccines and the persistent threat of future pandemics have made it necessary for novel vaccine design.…”

Clinical Advances in Viral-Vectored Influenza Vaccines

“…To address this need, influenza research over the past decade has focused on the discovery of new (universal) antigenic targets and improved vaccine modalities. Among the latter, those that have progressed into clinical trials are viral vectors, plasmid DNA ([ 97 ] and more), recombinant proteins [ 98 , 99 ], and polypeptide epitope sequences [ 100 , 101 , 102 ]. The focus of this review has been on viral vectors and their potential as strong candidates for protective influenza vaccines.…”

Progress in the Development of Universal Influenza Vaccines

“…In turn, FLU-v, developed by PepTcell (SEEK), is a peptide vaccine comprised of four synthetic peptides with conserved epitopes from influenza A and B strains designed to provide a broadly protective cellular immune response against influenza A and B. Results from phase IIb clinical trials showed that adjuvanted FLU-v recipients ( n = 40) were significantly less likely to develop mild to moderate influenza disease (MMID) following intranasal challenge of A/CA04/H1N1 vs. placebo ( n = 42) (32.5 vs. 54.8% p = 0.035) [ 69 , 70 , 71 ]. Nevertheless, overall the vaccine protection effect was poor.…”