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Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study.

ABSTRACT: FLU-v, developed by PepTcell (SEEK), is a peptide vaccine aiming to provide a broadly protective cellular immune response against influenza A and B. A randomized, double-blind, placebo-controlled, single-center, phase IIb efficacy and safety trial was conducted. One hundred and fifty-three healthy individuals 18-55 years of age were randomized to receive one or two doses of adjuvanted FLU-v or adjuvanted placebo subcutaneously on days -43 and -22, prior to intranasal challenge on day 0 with the A/California/04/2009/H1N1 human influenza A challenge virus. The primary objective of the study was to identify a reduction in mild to moderate influenza disease (MMID) defined as the presence of viral shedding and clinical influenza symptoms. Single-dose adjuvanted FLU-v recipients (n = 40) were significantly less likely to develop MMID after challenge vs placebo (n = 42) (32.5% vs 54.8% p = 0.035). FLU-v should continue to be evaluated and cellular immunity explored further as a possible important correlate of protection against influenza.

SUBMITTER: Pleguezuelos O

PROVIDER: S-EPMC7069936 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study.

Pleguezuelos Olga O James Emma E Fernandez Ana A Lopes Victor V Rosas Luz Angela LA Cervantes-Medina Adriana A Cleath Jason J Edwards Kristina K Neitzey Dana D Gu Wenjuan W Hunsberger Sally S Taubenberger Jeffery K JK Stoloff Gregory G Memoli Matthew J MJ

NPJ vaccines 20200313 1

FLU-v, developed by PepTcell (SEEK), is a peptide vaccine aiming to provide a broadly protective cellular immune response against influenza A and B. A randomized, double-blind, placebo-controlled, single-center, phase IIb efficacy and safety trial was conducted. One hundred and fifty-three healthy individuals 18-55 years of age were randomized to receive one or two doses of adjuvanted FLU-v or adjuvanted placebo subcutaneously on days -43 and -22, prior to intranasal challenge on day 0 with the ...[more]

PMID: 32194999

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Project description: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).

Project description:Previous reports demonstrated that FLU-v, a peptide-based broad-spectrum influenza vaccine candidate, induced antibody and cellular immune responses in humans. Here, we evaluate cellular effector functions and cross-reactivity. PBMC sampled pre- (day 0) and post-vaccination (days 42 and 180) from vaccine (n = 58) and placebo (n = 27) recipients were tested in vitro for responses to FLU-v and inactivated influenza strains (A/H3N2, A/H1N1, A/H5N1, A/H7N9, B/Yamagata) using IFN-γ and granzyme B ELISpot. FLU-v induced a significant increase in the number of IFN-γ- and granzyme-B-secreting cells responding to the vaccine antigens from pre-vaccination (medians: 5 SFU/106 cells for both markers) to day 42 (125 and 40 SFU/106 cells, p < 0.0001 for both) and day 180 (75 and 20 SFU/106 cells, p < 0.0001 and p = 0.0047). The fold increase from pre-vaccination to day 42 for IFN-γ-, granzyme-B-, and double-positive-secreting cells responding to FLU-v was significantly elevated compared to placebo (medians: 16.3-fold vs. 1.0-fold, p < 0.0001; 3.5-fold vs. 1.0-fold, p < 0.0001; 3.0-fold vs. 1.0-fold, p = 0.0012, respectively). Stimulation of PBMC with inactivated influenza strains showed significantly higher fold increases from pre-vaccination to day 42 in the vaccine group compared to placebo for IFN-γ-secreting cells reacting to H1N1 (medians: 2.3-fold vs. 0.8-fold, p = 0.0083), H3N2 (1.7-fold vs. 0.8-fold, p = 0.0178), and H5N1 (1.7-fold vs. 1.0-fold, p = 0.0441); for granzyme B secreting cells reacting to H1N1 (3.5-fold vs. 1.0-fold, p = 0.0075); and for double positive cells reacting to H1N1 (2.9-fold vs. 1.0-fold, p = 0.0219), H3N2 (1.7-fold vs. 0.9-fold, p = 0.0136), and the B strain (2.0-fold vs. 0.8-fold, p = 0.0227). The correlation observed between number of cells secreting IFN-γ or granzyme B in response to FLU-v and to the influenza strains supported vaccine-induced cross-reactivity. In conclusion, adjuvanted FLU-v vaccination induced cross-reactive cellular responses with cytotoxic capacity, further supporting the development of FLU-v as a broad-spectrum influenza vaccine.

Dataset Information

Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study.

Publications

Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study.

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