Preventive and therapeutic effects of recombinant IFN-alpha2b nasal spray on SARS-CoV infection in Macaca mulata / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the preventive and therapeutic effects of recombinant IFN-alpha2b for nasal spray on SARS-CoV infection in Macaca mulata (rhesus monkey).</p><p><b>METHODS</b>Ten rhesus monkeys were divided into two groups, 5 in interferon group, and 5 in control group. Before and after SARS-CoV attack, the virus was detected in samples such as pharyngeal swab in all the two groups by Real-time PCR (RT-PCR) and virus isolation was performed.</p><p><b>RESULTS</b>After virus attack, the level of SARS-CoV-specific IgG and neutralizing antibody were induced by SARS-CoV in the interferon group was weaker than in control group. Hematology items showed no apparent changes after virus attack in treated group. Through pathological examination, the morphology of the lung tissues of two Macaques in the treated group was normal, while the other three displayed the interstitial pneumonia with the thickened septum and infiltration with mononuclear cells. Among which, one monkey showed part of thickened septum fused with each other. These lesions in the interferon treated animals were similar to those seen in the animals in control group, but with smaller scope of pathological changes. No significant abnormity was detected in other organs.</p><p><b>CONCLUSION</b>Recombinant IFN-alpha2b could effectively interdict or weaken SARS-CoV injury in monkeys.</p>

A field trial for evaluating the safety of recombinant human interferon alpha-2b for nasal spray / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections.</p><p><b>METHODS</b>Field epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days.</p><p><b>RESULTS</b>During the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies.</p><p><b>CONCLUSION</b>Using recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.</p>

A field trial of recombinant human interferon alpha-2b for nasal spray to prevent SARS and other respiratory viral infections / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the preventive effect of recombinant human interferon alpha-2b for nasal spray against SARS and other common respiratory viral infections by serum-epidemiological method.</p><p><b>METHODS</b>A randomized, placebo-controlled, double-blind field trial study in populations with 14,391 persons from SARS prevalent cities or provinces in China during May-Jun, 2003 and Dec-Apr, 2004. Interferon alpha-2b was given twice per day, once 9 x 10(5) IU by nasal spray for 5 days. Serum samples were taken at 15 days after last administration. Serological tests included SARS IgG antibody and IgM antibodies against influenza B, parainfluenza virus types 1-3, adenovirus type 3, 7 and respiratory syncytial virus by using commercial ELISA kits.</p><p><b>RESULTS</b>No statistically significant difference in serum SARS IgG antibody positive rate was found between the interferon and control groups among 2,757 serum samples. On the other hand, after using interferon, all four respiratory viruses (parainfluenza virus types 1-3 influenza B, adenovirus types 3, 7 and respiratory syncytial virus) in interferon group had lower IgM antibody positive rates than those in control group. Among them there were statistically significant differences between the interferon and control groups for parainfluenza virus, influenza B and adenovirus. The preventive efficacy of interferon against four respiratory viruses was different, from high to low, the rank was Flu B (66.76%), parainfluenza types 1-3 (66.75%), RSV (39.61%) and adenovirus (32.86%). The average preventive efficacy was 50.27%.</p><p><b>CONCLUSION</b>The recombinant human interferon alpha-2b for nasal spray could decrease the rates of common respiratory viruses infection in the selected population.</p>

Preliminary study on nasal spray of interferon alpha-2b used for prevention of rubella and measles virus infections / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of the interferon alpha-2b nasal spray in prevention of rubella and measles virus infections.</p><p><b>METHODS</b>The properly selected volunteer groups have been divided into interferon alpha-2b experimental and control group. The experimental group received interferon alpha-2b treatment by nasal spray for 2 days before the immunization, then both groups were challenged with rubella and measles attenuated live vaccine respectively through nasal spray. The sera from pre-immunization and 21 and 28 days after immunization were collected to test the IgG antibody titers. The influence on the viral antibody titer reflects the viral preventive effect by interferon alpha-2b.</p><p><b>RESULTS</b>The antibody titer difference of measles virus between experimental and control group was 1.26 (21 day) and 2.96 (28 day), there were statistically difference between them; the difference of rubella virus was 0.95 (21 day) and 0.37 (28 day), but there were no statistically differences found.</p><p><b>CONCLUSION</b>The preliminary results showed that the interferon alpha-2b can be used as prevention method for measles and rubella viral infections.</p>

Anti-SARS virus activities of different recombinant human interferons in cell culture system / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study the anti-SARS virus activities of different recombinant human interferons on the cell culture system.</p><p><b>METHODS</b>Anti-SARS virus activities of interferons were determined by using CPE inhibition test in human skeletal muscle sarcoma (Rda) cell culture.</p><p><b>RESULTS</b>The average minimum amount of interferon alpha 2b, alpha 1b, beta 1b or omega 1b to inhibit 50% CPE in Rda cell culture was (160.5+/-129.5) IU/ml, (149.0+/-71.7) IU/ml, (69.5+/-61.5) IU/ml, (87.3+/-47.1) IU/ml, respectively or (0.6+/-0.5) ng/ml, (10.6+/-5.1) ng/ml, (3.5+/-3.1) ng/ml, (0.9+/-0.5) ng/ml, respectively.</p><p><b>CONCLUSION</b>All the tested recombinant interferons showed anti-SARS virus activities on the Rda cell culture with different sensitivities.</p>

Development of the cDNA chip for SARS virus and a primary study on the possible molecular mechanism of interferon alpha2b inhibiting the SARS virus replication / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study the molecular mechanism of interferon alpha2b(IFNalpha2b) inhibiting the SARS virus replication. SARS-associated coronavirus (SARS virus) cDNA chip was developed and applied to detect the virus RNA transcription levels in the interferon-treated and untreated cell cultures, and the mechanism of anti-SARS virus activity of interferon alpha2b in cell culture system was explored.</p><p><b>METHODS</b>SARS virus cDNA chip was prepared by comparing the published SARS virus genome sequence, and the cDNA chip was used to study the interferon alpha2b function during SARS virus replication.</p><p><b>RESULTS</b>SARS virus cDNA chip was successfully prepared by using PCR method. The results showed that the cDNA chip could be used to detect the viral RNA transcription level. Interferon alpha2b could inhibit almost all the SARS virus gene transcription. An unknown gene at the position 28130-28426 bp, named as U gene, may play an important role during the viral replication.</p><p><b>CONCLUSION</b>A SARS virus whole genome cDNA chip was established. It could be used to study the virus molecular biology and antiviral drug screening. The results also showed that interferon alpha2b could inhibit almost the whole virus gene transcription by using the cDNA chip.</p>