Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers

Higgins, P. G.; Phillpotts, R. J.; Scott, G.M.; Wallace, Jeffrey I.; Bernhardt, Leon; Tyrrell, D. A. J.

doi:10.1128/aac.24.5.713

Cited by 85 publications

(54 citation statements)

References 7 publications

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“…The activity of human interferon-a on monkey cells using different viruses in various investigations has been found to be much lower than the corresponding activity on human cells and greatly varying with the type of virus used (11 Á/13). The present results are therefore compatible with the possibility that the SARS-CoV is highly sensitive to the activity of human IFN-a, a possibility that is also suggested by the results of clinical studies on the effect of interferons on other human coronaviruses (14,15).…”

Section: Discussionsupporting

confidence: 90%

In vitro inhibition of SARS virus replication by human interferons

Dahl

Linde

Strannegård

2004

Scandinavian Journal of Infectious Diseases

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Four different types of human interferon, interferon-beta (IFN-beta), recombinant IFN-alpha2a and IFN-alpha2b and natural IFN-alpha were tested for antiviral activity against SARS-coronavirus. The experiments were performed using in vitro cultivated monkey Vero E6 cells. IFN-beta was found to be the most highly active antiviral agent, followed by natural IFN-alpha, whereas the 2 recombinant IFN-alpha2 species were poorly active in the system used. These results suggest that IFN-beta as well as natural IFN-alpha may be used for the treatment of SARS.

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Section: Discussionsupporting

confidence: 90%

In vitro inhibition of SARS virus replication by human interferons

Dahl

Linde

Strannegård

2004

Scandinavian Journal of Infectious Diseases

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“…Isolation, inoculation, monitoring and assessment procedures have been described elsewhere (Beare & Reed, 1977;Higgins et al 1983). Thirty-three volunteers, 12 males and 21 females, were inoculated intranasally with 89-407 TCID50 of the LP strain of coronavirus 229E, contained in a filtered nasal wash. Because they were the placebo group of a prophylactic drug trial they were treated with a selfadministered intranasal spray (three times daily for 4 days) containing buffer and human albumen.…”

Section: Volunteersmentioning

confidence: 99%

“…Resistance to human coronavirus Specific and total immunoglobulins in sera Neutralizing antibody to LP virus was measured by a micro-neutralization test (Higgins et al 1983) in C-16 cells.…”

Section: Specimensmentioning

confidence: 99%

Effect of specific humoral immunity and some non-specific factors on resistance of volunteers to respiratory coronavirus infection

Callow

1985

J. Hyg.

118

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SUMMARYThirty-three volunteers were inoculated intranasally with coronavirus 229E, and their responses monitored by antibody rises, symptomatology and virus excretion. These were related to their pre-trial immune status as indicated by concentrations of specific antibodies and non-specific proteins in serum and nasal washings. Both circulating and local specific antibodies were associated with protection from infection and disease, but only specific IgA antibodies of either type appeared to shorten the period of virus shedding. Although total secretory IgA was significantly associated only with reduction of symptoms, total protein in nasal washings appeared to protect against infection also, indicating that other locally produced proteins, not identified, may be associated with resistance.Two of the many factors which may affect the concentration of circulating and local protective proteins and thus influence the outcome of virus inoculation, namely, sex of the volunteer and the interval since the previous cold, were examined. Male volunteers or volunteers who had had evidence of a recent respiratory infection were less likely to be infected, but if they were infected, they had lower clinical scores and stopped shedding virus earlier than the rest. These groups possessed higher concentrations of specific antibodies and non-specific proteins in their pre-challenge sera and/or nasal washings. The significance of these findings is discussed.

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“…IFNs inhibit viral infection by directly interfering with viral replication and by inducing both an innate and adaptive immune response to infection. IFN-αs are effective in the treatment of hepatitis B and C [7,8] and respiratory coronavirus infections unrelated to the Urbani strain of SARS-CoV [9][10][11][12]. , and combinations of 18] are effective in inhibiting SARS-CoV replication in vitro.…”

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confidence: 99%

Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

et al. 2006

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Cell Research | www.cell-research.com Antiviral effects of IFN-α against MHV-1 220 npg ORIGINAL ARTICLE IntroductionIn March 2003, a number of laboratories independently reported the isolation and characterization of a novel coronavirus (CoV) from specimens of patients with severe acute respiratory syndrome (SARS) [1,2]. Although an effective therapeutic strategy against SARS has yet to be developed, interferons (IFN) are recognized to play critical roles in host resistance to viral infection [3][4][5][6], thereby implicating them as potential candidates for SARS CoV treatment. IFNs inhibit viral infection by directly interfering with viral replication and by inducing both an innate and adaptive immune response to infection. IFN-αs are effective in the treatment of hepatitis B and C [7,8] and respiratory coronavirus infections unrelated to the Urbani strain of SARS-CoV [9][10][11][12]. , and combinations of 18] are effective in inhibiting SARS-CoV replication in vitro. Moreover, it was reported that macacque monkeys were protected from infection with SARS CoV by treatment with .IFN alfacon-1 (Infergen, Intermune Corp, Brisbane, California), a synthetic IFN-α designed to represent a consensus , has been shown in both cell culture systems [21] and comparative clinical trials [22] to inhibit viral replication more potently than other IFN-αs. Based on these findings, a pilot study to evaluate the potential clinical benefit and safety of IFN alfacon-1 in SARS treatment was conducted by our laboratory. Interferon (IFN)-αs bind to and activate their cognate cell surface receptor to invoke an antiviral response in target cells. Well-described receptor-mediated signaling events result in transcriptional regulation of IFN sensitive genes, effectors of this antiviral response. Results from a pilot study to evaluate the clinical efficacy of IFN-α treatment of SARS patients provided evidence for IFN-inducible resolution of disease. In this report we examined the contribution of IFN-inducible phosphorylation-activation of specific signaling effectors to protection from infection by a SARS-related murine coronavirus, MHV-1. As anticipated, the earliest receptor-activation event, Jak1 phosphorylation, is critical for IFN-inducible protection from MHV-1 infection. Additionally, we provide evidence for the contribution of two kinases, the MAP kinase p38MAPK, and protein kinase C (PKC) d to antiviral protection from MHV-1 infection. Notably, our data suggest that MHV-1 infection, as for the Urbani SARS coronoavirus, inhibits an IFN response, inferred from the lack of activation of pkr and 2'5'-oas, genes associated with mediating the antiviral activities of IFN-αs. To identify potential target genes that are activated downstream of the IFN-inducible signaling effectors we identified, and that mediate protection from coronavirus infection, we examined the gene expression profiles in the peripheral blood mononuclear cells of SARS patients who received IFN treatment. A subset of differentially regulated genes were distinguished with...

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Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers

Cited by 85 publications

References 7 publications

In vitro inhibition of SARS virus replication by human interferons

In vitro inhibition of SARS virus replication by human interferons

Effect of specific humoral immunity and some non-specific factors on resistance of volunteers to respiratory coronavirus infection

Characterization of the antiviral effects of interferon-α against a SARS-like coronoavirus infection in vitro

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