Priming by a novel universal influenza vaccine (Multimeric-001)—A gateway for improving immune response in the elderly population

Atsmon, Jacob; Caraco, Yoseph; Ziv-Sefer, Sagit; Shaikevich, Dimitry; Abramov, Ester; Volokhov, Inna; Bruzil, Svetlana; Haima, Kirsten Y.; Gottlieb, Tanya M.; Ben-Yedidia, Tamar

doi:10.1016/j.vaccine.2014.08.031

Cited by 79 publications

(72 citation statements)

References 32 publications

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“…[21] These studies showed that TIV, which was administrated 3 weeks after receiving 1 or 2 administrations of M-001 or placebo, with an interval of 21 ± 2 days, induced higher HAI antibody titers in individuals primed with M-001. In addition, M-001 also increased the TIV seroconversion rate (percentage of participants with a minimum 4-fold increase in the HAI titer and ≥1:40 HAI antibody titers) and broadens the antibody responses toward influenza strains other than the TIV strains.…”

Section: Discussionmentioning

confidence: 99%

“…The vaccine production takes only 6 to 8 weeks and it has the possibility of flexible manufacturing year-round, meaning that production can be planned in accordance with market demands, enabling national stockpiles to be maintained for all income class countries. [20,21,35] Furthermore, people with egg-allergies can be vaccinated with the standalone vaccine as the vaccine is not produced in embryonated chicken eggs. [1] …”

Section: Discussionmentioning

confidence: 99%

“…[24,25] We estimated a background rate of 5% in the placebo group and it is expected that the M-001 vaccine will result in at least 5 times higher rates, or an absolute rate of 25% responders in the vaccinated arms. [21] To be able to detect this with a power of 80%, approximately 60 subjects per arm are needed based on a 2-group continuity corrected test with a 0.05 two-sided significance level. Taking 15% loss of follow-up into account, a total of 222 subjects (74 subjects per treatment group) is required.…”

Section: Method/designmentioning

confidence: 99%

“…The vaccine induces both humoral and cellular immunity. [20,21] In this phase IIb trial, the immunogenicity and safety of M-001 and its administration prior to an aluminum phosphate gel (AlPO 4 )-adjuvanted H5N1 investigational influenza vaccine product (Fluart Innovative Vaccines Ltd., Hungary) will be evaluated in healthy adults (aged 18–60 years). Fluart H5N1 vaccine is highly immunogenic at doses of 6 and 12 μg and hence, a suboptimal dose of the vaccine (3 μg) will be used to evaluate the dose sparing potential of M-001 and to show its ability to enhance immunogenicity of the strain-specific vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine

et al. 2017

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Introduction:Influenza is a major respiratory viral infection of humans with high mortality and morbidity rates and profound economic impact. Although influenza vaccines are generally updated yearly to match the viruses expected in the coming season, genetic mutation and reassortment can result in unexpected novel strains. Therefore, it is important to develop universal vaccines inducing protective immunity to such strains before they appear. This clinical trial is designed to evaluate the safety and immunogenicity of Multimeric-001 (M-001), which contains conserved epitopes of influenza A and B. M-001 is able to induce both humoral and cellular immunity and provides broad strain coverage.Methods:In a multicenter, randomized, double-blind, and controlled phase IIb trial, 222 healthy volunteers aged 18 to 60 years will be randomized into 3 groups (1:1:1) to receive either 2 intramuscular injections of 0.5 mg M-001 (arm 1), 1.0 mg M-001 (arm 2), or saline (arm 3—placebo), before receiving an investigational (whole virus, inactivated, aluminum phosphate gel [AlPO4]-adjuvanted) prepandemic influenza vaccine (H5N1). Primary outcomes are safety and cellular immune responses (cell-mediated immunity [CMI]) induced by M-001, evaluated by multiparametric flow cytometry of intracellular cytokines. The secondary outcome is the serum hemagglutination inhibition (HAI) titer toward the H5N1 vaccine strain. Additionally, exploratory outcomes include evaluation of CMI by quantitative reverse transcription polymerase chain reaction of cytokine mRNA, HAI titers toward H5-drifted strains, serum single radial hemolysis titers toward the H5N1 study vaccine, and the association between CMI markers and antibody response.Discussion:There is a need for influenza vaccines that give the population a broader protection against multiple strains of influenza virus. M-001 might be such vaccine which will be tested in this current trial as a standalone vaccine and as a pandemic primer. Both cellular and humoral immune responses will be evaluated.Trial registration:EudraCT number: 2015-001979-46.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Method/designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine

et al. 2017

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“…Some epitope-based influenza vaccines are already in clinical trials. One, Multimeric-001, which consists of a single recombinant protein composed of B and T cell epitopes, is seen to induce both cellular and humoral immunity (Atsmon et al , 2014; Gottlieb and Ben-Yedidia, 2014). Although such trials have been small, they are promising, inducing cross protective immunity without severe side effects.…”

Section: Introductionmentioning

confidence: 99%

Towards the knowledge-based design of universal influenza epitope ensemble vaccines

et al. 2016

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Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes.Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes.Availability and Implementation: http://imed.med.ucm.es/Tools/episopt.html.Contact: d.r.flower@aston.ac.uk

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Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

Dong

Bhide

Marsman

et al. 2018

Biotechnology Journal

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Induction of CD8 cytotoxic T cells (CTLs) to conserved internal influenza antigens, such as nucleoprotein (NP), is a promising strategy for the development of cross-protective influenza vaccines. However, influenza NP protein alone cannot induce CTL immunity due to its low capacity to activate antigen-presenting cells (APCs) and get access to the MHC class I antigen processing pathway. To facilitate the generation of NP-specific CTL immunity the authors develop a novel influenza vaccine consisting of virosomes with the Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) and the metal-ion-chelating lipid DOGS-NTA-Ni incorporated in the membrane. In vitro, virosomes with incorporated MPLA induce stronger activation of APCs than unadjuvanted virosomes. Virosomes modified with DOGS-NTA-Ni show high conjugation efficacy for his-tagged proteins and facilitate efficient uptake of conjugated proteins by APCs. Immunization of mice with MPLA-adjuvanted virosomes with attached NP results in priming of NP-specific CTLs while MPLA-adjuvanted virosomes with admixed NP are inefficient in priming CTLs. Both vaccines induce equally high titers of NP-specific antibodies. When challenged with heterosubtypic influenza virus, mice immunized with virosomes with attached or admixed NP are protected from severe weight loss. Yet, unexpectedly, they show more weight loss and more severe disease symptoms than mice immunized with MPLA-virosomes without NP. Taken together, these results indicate that virosomes with conjugated antigen and adjuvant incorporated in the membrane are effective in priming of CTLs and eliciting antigen-specific antibody responses in vivo. However, for protection from influenza infection NP-specific immunity appears not to be advantageous.

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Priming by a novel universal influenza vaccine (Multimeric-001)—A gateway for improving immune response in the elderly population

Cited by 79 publications

References 32 publications

Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine

Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine

Towards the knowledge-based design of universal influenza epitope ensemble vaccines

Monophosphoryl Lipid A‐Adjuvanted Virosomes with Ni‐Chelating Lipids for Attachment of Conserved Viral Proteins as Cross‐Protective Influenza Vaccine

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