Anti‐adenoviral effect of interferon‐β and interferon‐γ in serotypes that cause acute keratoconjunctivitis

Uchio, Eiichi; Inoue, Hirotoshi; Fuchigami, Aki; Kadonosono, Kazuaki

doi:10.1111/j.1442-9071.2010.02457.x

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Since IFN-α appears not to directly affect AdHu5 transgene expression 38 , it seems more likely that IFN-β is mediating this effect. In addition, human IFN-β has been described to have a detrimental effect on the replication of different adenoviral serotypes in vitro 39 .…”

Section: Discussionmentioning

confidence: 99%

STING-pathway modulation to enhance the immunogenicity of adenoviral-vectored vaccines

Padron-Regalado

Ulaszewska

Douglas

et al. 2022

Sci Rep

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Traditional chemical adjuvants remain a practical means of enhancing the immunogenicity of vaccines. Nevertheless, it is recognized that increasing the immunogenicity of viral vectors is challenging. Recently, STING ligands have been shown to enhance the efficacy of different vaccine platforms, but their affectivity on viral-vectored vaccination has not been fully assessed. In this study we used a multi-pronged approach to shed light on the immunological properties and potential mechanisms of action of this type of adjuvant and focused our study on replication-deficient human adenovirus serotype 5 (AdHu5). When the STING ligand 2′3′-cGAMP was mixed with AdHu5, the adjuvant enhanced anti-vector immune responses while decreasing the transgene-specific CD8+ T cell response. Studies employing STING-knockout mice and a 2′3′-cGAMP inactive analogue confirmed the aforementioned effects were STING dependent. In vitro assays demonstrated 2′3′-cGAMP induced the production of IFN-β which in turn negatively affected AdHu5 transgene expression and CD8+ T cell immunogenicity. In an effort to overcome the negative impact of early 2′3′-cGAMP signaling on AdHu5 transgene immunogenicity, we generated a bicistronic vector encoding the 2′3′-cGAMP together with a model antigen. Intracellular production of 2′3′-cGAMP after AdHu5 infection was able to enhance transgene-specific CD8+ T cell immunogenicity, although not to a level that would warrant progression of this adjuvant to clinical assessment. This work highlights the importance of timing of 2′3′-cGAMP administration when assessing its adjuvant capacity with different vaccine modalities.

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Section: Discussionmentioning

confidence: 99%

STING-pathway modulation to enhance the immunogenicity of adenoviral-vectored vaccines

Padron-Regalado

Ulaszewska

Douglas

et al. 2022

Sci Rep

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“…No specific antiviral drugs are currently available for the treatment of EKC or any other infection caused by adenoviruses. Interestingly, it has been suggested that five strains of different serotypes of adenovirus, types 3 (AdV3; species B), 4 (species E), 8, 19a and 37 (species D) involved in acute keratoconjunctivitis are highly inhibited by IFN-b and IFN-g in the A549 cell line, [2] However, IFN therapy in adenoviral keratoconjunctivitis has not been evaluated in clinical trials yet.…”

Section: Novel Therapies In Infectious Keratoconjunctivitis 21 Intementioning

confidence: 99%

Treatments in Infectious and Allergic Conjunctivitis: Is Immunomodulation the Future?

Santacruz¹,

Pérez‐Tapia²,

Castaneda³

et al. 2013

Common Eye Infections

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Thκ ocular surλacκ is a λunctional unit mainly λormκd by thκ conjunctival and cornκal κpi-thκlium structural componκnt , and tκar λilm solublκ componκnt . Microorganisms and κnvironmκntal allκrgκns can intκract with thκ tκar λilm, rκach thκ structural componκnt and gκnκratκ an immunκ rκsponsκ against thκm. Undκrstanding thκ cκllular and solublκ mκdiators that arκ involvκd in thκsκ inλlammatory rκsponsκs not only hκlps in undκr-standing thκ mκchanisms oλ currκnt trκatmκnts, but also is nκκdκd to idκntiλication and dκvκlopmκnt oλ nκw thκrapκutics targκts. Thκ aim oλ this rκviκw was to invκstigatκ thκ novκl and dκvκloping thκrapiκs, with spκcial κmphasis in immunomodulatory drugs/ molκculκs that could havκ somκ clinical indication in thκ trκatmκnt oλ inλκctious and allκr-gic conjunctivitis in λκw yκars. . Novel therapies in infectious keratoconjunctivitis . . Interferons IFN and adenoviral conjunctivitisIntκrλκrons wκrκ λirst dκscribκd as thκ major κλλκctor cytokinκs oλ thκ host immunκ rκsponsκ against viral inλκctions. IFN arκ wκll rκcognizκd by thκir potκnt antiviral propκrtiκs, howκv-κr IFN production is also inducκd in rκsponsκ to bactκrial ligands oλ innatκ immunκ rκcκp-tors and/or bactκrial inλκctions, indicating a broadκr physiological rolκ λor thκsκ cytokinκs in host dκλκncκ and homκostasis than was originally dκscribκd. Thrκκ main typκs oλ cytokinκs composκ thκ IFN λamily typκ I, typκ II and typκ III IFN. Typκ I IFN λamily is composκd oλ mκmbκrs, namκly IFN subtypκs, IFN , IFNε, IFN and IFNω. "y contrast, thκ typκ II IFN λamily includκs only onκ cytokinκ IFN , which also κxhibits antiviral activitiκs. Thκ third typκ oλ IFN is thκ IFN λamily, which includκs IFN also known as IL-, IFN also known as IL-" and IFN also known as IL-" . On thκ basis oλ protκin sκquκncκ and structurκ, typκ III IFN arκ markκdly diλλκr-κnt λrom typκ I and typκ II IFN and arκ morκ similar to mκmbκrs oλ thκ intκrlκukin-ILλamily howκvκr, thκy provokκ antiviral rκsponsκs and inducκ thκ activation oλ IFNstimulatκd gκnκs. [ ] Epidκmic kκratoconjunctivitis EKC is a sκvκrκ ocular inλκction, causκd by highly contagious adκnovirusκs "d , "d , and "d . "dκnoviral inλκction oλ thκ κyκ inducκs kκratitis and conjunctivitis, accompaniκd by pain, lacrimation, rκd and swollκn κyκ, as wκll as dκ-crκasκd vision that may last λor months or κvκn yκars. No spκciλic antiviral drugs arκ currκntly availablκ λor thκ trκatmκnt oλ EKC or any othκr inλκction causκd by adκnovirusκs. Intκrκstingly, it has bκκn suggκstκd that λivκ strains oλ diλλκrκnt sκrotypκs oλ adκnovirus, typκs "dV spκciκs " , spκciκs E , , a and spκciκs D involvκd in acutκ kκrato-conjunctivitis arκ highly inhibitκd by IFN-b and IFN-g in thκ "cκll linκ, [ ] Howκvκr, IFN thκrapy in adκnoviral kκratoconjunctivitis has not bκκn κvaluatκd in clinical trials yκt. . . Glycan interactions and EKCThκ initial κvκnt lκading to EKC is binding oλ thκ virusκs to glycans that contain sialic acid moiκtiκs on κpithκlial cκlls in thκ cornκa or conjunctiva through trimκric λibκr structurκs κx-tκnding λrom thκ v...

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“…Adenovirus vaccines are not used due to their proven oncogenicity [19]. In vitro studies on models of different viruses have shown the antiviral effect of natural interferons, as well as immunoglobulin G [20]. In this regard, the use of drugs that activate non-specific immune response factors and thus increase the body's overall resistance may be appropriate for the treatment and prevention of SARS [20][21][22].…”

mentioning

confidence: 99%

“…In vitro studies on models of different viruses have shown the antiviral effect of natural interferons, as well as immunoglobulin G [20]. In this regard, the use of drugs that activate non-specific immune response factors and thus increase the body's overall resistance may be appropriate for the treatment and prevention of SARS [20][21][22]. Drugs with immunomodulatory and so-called secondary antiviral action are widely studied [2,7,[23][24][25][26][27].…”

mentioning

confidence: 99%

Anti-Adenovirus Activity of the Medical Intranasal Drug Nazoferon

Povnitsa¹,

Biliavska²,

Pankivska³

et al. 2021

Mikrobiol. Z.

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Currently, 90 different types of human adenoviruses (HAdV) are known, which have been classified into seven species from A to G and new adenovirus types continue to emerge. Antigenic diversity of viruses inhibits the process of creating universal vaccines and causes the development of resistance to direct-acting antiviral drugs. In addition to the rapid development of drug resistance, too narrow a range of existing drugs and a significant number of side effects limits the treatment of adenoviral infections. There is currently no specific etiotropic antiviral drug. Therefore, the development of new effective drugs and the selection of the optimal drug for the treatment of infections caused by adenoviruses remain relevant. The aim of the study was to investigate the antiviral properties of the drugs Nazoferon spray and Nazoferon drops in a model of human adenovirus serotype 3. Methods. Determination of cytotoxicity and antiviral action of drugs was performed by standard colorimetric method using MTT. The titer of the virus, synthesized in the presence of drugs was determined by the end point of dilution of the virus, which causes 50% development of the cytopathic effect of the virus on cells (СPE). Results. Low cytotoxicity of Nazoferon spray and Nazoferon drops (manufactured by JSC Farmak, Ukraine) was shown, CC50 is 53854 IU/ml and 54357 IU/ml, respectively. Quantitative and qualitative composition of excipients had no cytotoxic effect. In prophylactic regimens, interferon preparations did not inhibit the reproduction of adenovirus in vitro. Taking into account that most of the virions remain associated with the cells during the reproduction of adenovirus in the cell, we used test to determine infectivity lysates of infected and treated cells. The infectious titer of the synthesized HAdV3 was reduced by 3.2 log10 and 3.7 log10 for Nazoferon spray and drops, respectively. Conclusions. Nazoferon spray and drops can be recommended as anti-adenoviral drugs that block the reproduction of adenovirus, and due to their bioavailability and low cost have significant advantages in the treatment of acute respiratory infections (ARIs) caused by human adenoviruses.

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Anti‐adenoviral effect of interferon‐β and interferon‐γ in serotypes that cause acute keratoconjunctivitis

Abstract: These results suggest that both interferon-β and interferon-γ have anti-adenoviral activity in vitro. Interferons have the potential to be used for local treatment of adenoviral keratoconjunctivitis, although further evaluation in animal models and clinical trials is necessary.

Cited by 12 publications

References 26 publications

STING-pathway modulation to enhance the immunogenicity of adenoviral-vectored vaccines

STING-pathway modulation to enhance the immunogenicity of adenoviral-vectored vaccines

Treatments in Infectious and Allergic Conjunctivitis: Is Immunomodulation the Future?

Anti-Adenovirus Activity of the Medical Intranasal Drug Nazoferon

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