Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses

Li, Junwei; Arévalo, Maria T.; Chen, Yanping; Posadas, Olivia; Smith, Jacob; Zeng, Mingtao

doi:10.4161/hv.28407

Cited by 16 publications

(18 citation statements)

References 51 publications

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“…In contrast, vaccination with EFn‐3×M2e‐HA2 plus PA protected 100% of mice from challenge with PR8 virus and 88% of mice from challenge with CA09 virus. Based on one of our previous studies, we predict that this formulation can also protect against H3N2 viruses. We also predict, based on cross‐reactive antibody responses to H5N1 avian M2 and HA2 that this vaccine may also protect against H5N1 viruses.…”

Section: Discussionmentioning

confidence: 98%

“…The most common amino acids in each position were used to create an artificial, centralized, HA2 sequence. Next, a tandem of M2es from A/California/04/2009 (H1N1), A/Hong Kong/1/1968 (H3N2) and A/Vietnam/1204/2004 (H5N1) influenza viruses was created and linked with the centralized HA2 as previously described . The anthrax EFn gene sequence was added upstream of the 3×M2e‐HA2 (Table ).…”

Section: Methodsmentioning

confidence: 99%

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A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax

Arévalo

Díaz-Arévalo

et al. 2016

Immunology

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Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of three tandem M2e repeats plus HA2, in combination with a detoxified anthrax oedema toxin delivery system (EFn plus PA) to enhance immune responses. The EFn-3×M2e-HA2 plus PA vaccine formulation elicited robust, antigen-specific, IgG responses; and was protective against heterologous influenza viral challenge when intranasally delivered to mice three times. Moreover, use of the detoxified anthrax toxin system as an adjuvant had the additional benefit of generating protective immunity against anthrax. Hence, this novel vaccine strategy could potentially address two major emerging public health and biodefence threats.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax

Arévalo

Díaz-Arévalo

et al. 2016

Immunology

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“…The challenged mice were monitored for clinical symptoms and survival. ELISA and micro-neutralization were performed as we have previously described[24]. …”

Section: Methodsmentioning

confidence: 99%

Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA

Arévalo

Díaz-Arévalo

et al. 2015

Journal of Controlled Release

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Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 104 fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines.

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“…According to a study conducted by Li et al (2), using an M2e peptide fused to HA2 could improve universal influenza vaccine potency in inducing a cross-reactive immune response against various subtypes of influenza viruses compared to using M2e or HA2 solely. Mice imCopyright © 2018, Author(s).…”

Section: Introductionmentioning

confidence: 99%

“…Traditional influenza vaccines are based on immunity to the surface glycoproteins that are highly variable among different types of influenza viruses; so, an annual reformulation is needed. The best way to protect people against unforeseen pandemic influenza is to develop an improved universal vaccine using most conserved influenza virus antigens (1,2). The universal influenza vaccine can induce an immune response, which provides not only protection against the homologous virus but also a cross-protection against infections with various subtypes of influenza virus strains, in particular, zoonotic highly pathogenic avian influenza viruses which have been verified to be able to infect humans (3).…”

Section: Introductionmentioning

confidence: 99%

In Silico Analysis and Expression of Influenza Virus 3M2e-HA2 Chimer Protein Fused to C-Terminal Domain of Leishmania major HSP70

Nazeri

Farahmand

Fotouhi

et al. 2018

Jundishapur J Microbiol

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Background: Design and construction of a universal vaccine based on conserved influenza antigens is the best way to protect populations from unforeseen influenza outbreaks. The ectodomain of matrix protein 2 (M2e) and hemagglutinin stalk domain (HA2) are considered as conserved influenza antigens. Genetic linkage of adjuvant HSP70 to these antigens can improve the efficacy of the vaccine. Objectives: The aim of this study was to produce a chimer protein to confer cross-protection against different subtypes of influenza A virus. Methods: The chimer form was subjected to in silico modeling and Immunoinformatics prediction analysis. The heat shock protein 70 (HSP70c) gene was cloned into the pET28a vector downstream of 3M2e-HA2 and expressed in Escherichia coli host. The desired chimer protein was purified with the Ni-TED column. Results: Validation analysis of the tertiary structure model showed that the model is in the range of native conformations. High score epitopes by Immunoinformatics tools were predicted. The expression of purified 3M2e-HA2-HSP70c was confirmed by the western-blotting assay. Conclusions:The genetic fusion of adjuvant HSP70 to the target antigen may improve the stimulation of immune responses. In silico analysis revealed the appropriate epitopes characterization of conserved antigens. Hence, the constructed chimer protein could be considered as a potential universal vaccine candidate to protect against influenza infection.

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Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses

Cited by 16 publications

References 51 publications

A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax

A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax

Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA

In Silico Analysis and Expression of Influenza Virus 3M2e-HA2 Chimer Protein Fused to C-Terminal Domain of Leishmania major HSP70

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