Return of inactivated whole‐virus vaccine for superior efficacy

Furuya, Yasubumi

doi:10.1038/icb.2011.70

Cited by 52 publications

(48 citation statements)

References 160 publications

(180 reference statements)

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“…Due to the lack of replication, it seems that recognition of viral PAMPs only occurs through innate immune cell receptors, such as TLR7 and retinoic acid‐inducible gene 1 (RIG 1), which stimulates IFN type‐1, and subsequently enhances the cross‐presentation pathway and Th1 responses. On the other hand, uncoating and release of the viral components into the host cytosol may provide an antigen source for MHC class 1 presentation, priming the CTLs (Figure ) …”

Section: Inactivation Methodsmentioning

confidence: 99%

Inactivation methods for whole influenza vaccine production

Sabbaghi

Miri

Keshavarz

et al. 2019

Reviews in Medical Virology

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Summary Despite tremendous efforts toward vaccination, influenza remains an ongoing global threat. The induction of strain‐specific neutralizing antibody responses is a common phenomenon during vaccination with the current inactivated influenza vaccines, so the protective effect of these vaccines is mostly strain‐specific. There is an essential need for the development of next‐generation vaccines, with a broad range of immunogenicity against antigenically drifted or shifted influenza viruses. Here, we evaluate the potential of whole inactivated vaccines, based on chemical and physical methods, as well as new approaches to generate cross‐protective immune responses. We also consider the mechanisms by which some of these vaccines may induce CD8+ T‐cells cross‐reactivity with different strains of influenza. In this review, we have focused on conventional and novel methods for production of whole inactivated influenza vaccine. As well as chemical modification, using formaldehyde or β‐propiolactone and physical manipulation by ultraviolet radiation or gamma‐irradiation, novel approaches, including visible ultrashort pulsed laser, and low‐energy electron irradiation are discussed. These two latter methods are considered to be attractive approaches to design more sophisticated vaccines, due to their ability to maintain most of the viral antigenic properties during inactivation and potential to produce cross‐protective immunity. However, further studies are needed to validate them before they can replace traditional methods for vaccine manufacturing.

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Section: Inactivation Methodsmentioning

confidence: 99%

Inactivation methods for whole influenza vaccine production

Sabbaghi

Miri

Keshavarz

et al. 2019

Reviews in Medical Virology

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“…Most prominently, gamma- or high-energy electron radiation are being used for pathogen inactivation, but so far no human vaccine produced this way is available. Ionizing radiation has the advantages of working very quickly and, under conditions used for vaccine development, it preferentially damages nucleic acids rather than proteins, resulting in inactivated pathogens that are highly versatile to elicit effective immune responses [9,10,11]. Gamma radiation is emitted by a radioisotope and is able to efficiently penetrate liquids and solid materials.…”

Section: Introductionmentioning

confidence: 99%

Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses

Fertey

Bayer

Grünwald

et al. 2016

Viruses

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Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or β-propiolactone. This is a time-consuming process, the inactivation efficiency displays high variability and extensive downstream procedures are often required. Moreover, application of chemicals alters the antigenic components of the viruses or bacteria, resulting in reduced antibody specificity and therefore stimulation of a less effective immune response. An alternative method for inactivation of pathogens is ionizing radiation. It acts very fast and predominantly damages nucleic acids, conserving most of the antigenic structures. However, currently used irradiation technologies (mostly gamma-rays and high energy electrons) require large and complex shielding constructions to protect the environment from radioactivity or X-rays generated during the process. This excludes them from direct integration into biological production facilities. Here, low-energy electron irradiation (LEEI) is presented as an alternative inactivation method for pathogens in liquid solutions. LEEI can be used in normal laboratories, including good manufacturing practice (GMP)- or high biosafety level (BSL)-environments, as only minor shielding is necessary. We show that LEEI efficiently inactivates different viruses (influenza A (H3N8), porcine reproductive and respiratory syndrome virus (PRRSV), equine herpesvirus 1 (EHV-1)) and bacteria (Escherichia coli) and maintains their antigenicity. Moreover, LEEI-inactivated influenza A viruses elicit protective immune responses in animals, as analyzed by virus neutralization assays and viral load determination upon challenge. These results have implications for novel ways of developing and manufacturing inactivated vaccines with improved efficacy.

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“…While gamma irradiation can conserve viral antigenic epitopes [83], and irradiated Filoviruses [84], [85] have been used to detect polyclonal antibody responses in animal challenges and human survivors [86], recent studies reveal the doses used for Filovirus inactivation (approx. 3e+6 rads) can degrade epitope, protein and particle structures of several viruses including vesicular stomatitis virus (VSV) and Venezuelan equine encephalitis virus [87], [88].…”

Section: Resultsmentioning

confidence: 99%

Ebolavirus Nucleoprotein C-Termini Potently Attract Single Domain Antibodies Enabling Monoclonal Affinity Reagent Sandwich Assay (MARSA) Formulation

Sherwood

Hayhurst

2013

PLoS ONE

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BackgroundAntigen detection assays can play an important part in environmental surveillance and diagnostics for emerging threats. We are interested in accelerating assay formulation; targeting the agents themselves to bypass requirements for a priori genome information or surrogates. Previously, using in vitro affinity reagent selection on Marburg virus we rapidly established monoclonal affinity reagent sandwich assay (MARSA) where one recombinant antibody clone was both captor and tracer for polyvalent nucleoprotein (NP). Hypothesizing that the closely related Ebolavirus genus may share the same Achilles' heel, we redirected the scheme to see whether similar assays could be delivered and began to explore their mechanism.Methods and FindingsIn parallel we selected panels of llama single domain antibodies (sdAb) from a semi-synthetic library against Zaire, Sudan, Ivory Coast, and Reston Ebola viruses. Each could perform as both captor and tracer in the same antigen sandwich capture assay thereby forming MARSAs. All sdAb were specific for NP and those tested required the C-terminal domain for recognition. Several clones were cross-reactive, indicating epitope conservation across the Ebolavirus genus. Analysis of two immune shark sdAb revealed they also targeted the C-terminal domain, and could be similarly employed, yet were less sensitive than a comparable llama sdAb despite stemming from immune selections.ConclusionsThe C-terminal domain of Ebolavirus NP is a strong attractant for antibodies and enables sensitive sandwich immunoassays to be rapidly generated using a single antibody clone. The polyvalent nature of nucleocapsid borne NP and display of the C-terminal region likely serves as a bountiful affinity sink during selections, and a highly avid target for subsequent immunoassay capture. Combined with the high degree of amino acid conservation through 37 years and across wide geographies, this domain makes an ideal handle for monoclonal affinity reagent driven antigen sandwich assays for the Ebolavirus genus.

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Return of inactivated whole‐virus vaccine for superior efficacy

Cited by 52 publications

References 160 publications

Inactivation methods for whole influenza vaccine production

Inactivation methods for whole influenza vaccine production

Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses

Ebolavirus Nucleoprotein C-Termini Potently Attract Single Domain Antibodies Enabling Monoclonal Affinity Reagent Sandwich Assay (MARSA) Formulation

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