The Effects From Oral Administration of Recombinant Interferon-alpha on Piglet Daily Care

The administration of interferon has improved the antiviral and immunomodulatory abilities of piglets, which is conductive to conductive to the prevention of potential diseases or delay the appearance of clinical symptoms. This study aimed to evaluate the effects from administration of recombinant interferon-alpha (IFN-α) on the daily care of piglets. The results were compared with compound Chinese herbal, which was proved to improve serum interferon level. Further, the administration routes were compared between oral administration and intramuscular injection. Forty (40) piglets with equal age and weight were randomly divided into four groups: Control group (Group C, without treatment), Group H (treated with compound Chinese herbal), Group K (administered orally with recombinant IFN-α, 1500 IU per day per piglet), and Group J (administered intramuscularly with IFN-α, 4× 106 IU per day per piglet). After the treatment of 15 days, both oral and intramuscular treatment of recombinant IFN-α significantly improved the secretion of IFN-gamma (IFN-γ) (P<0.05), and the effects of intramuscular pathway were faster. In addition, the expression levels of IFN-stimulated genes (MX1 and ISG15) were significantly enhanced (P<0.01), independently of IFN-α treatment time and serum IFN-γ level. Different from other studies, compound Chinese herbal showed weaker effects on interferon stimulation in piglets. The results indicated that oral administration of recombinant IFN-α improved interferon-induced response of piglets at both serum and molecular levels, which may be applied for improving autoimmunity of piglets.

Effect of immune drugs to treat acute viral nasopharyngitis

The task in treating acute nasopharyngitis (ANP) deals with reducing the disease symptoms and the risk of complications. The lack of reliable antiviral drugs makes it important to search for appropriate medicines among other pharmacotherapeutic groups.The study involves a comparative analysis of the efficiency and estimates potential: the recombinant interferon α2b and the compound containing fungal β-D-glucans used in treat ANPThe studies involved patients with ANP from 18 to 55 years old. As many as 152 people were examined including the following: 38 were practically healthy people (group 1); and 114 patients wuth ANP: 38 people (group 2) was subject to a standard therapy (vasoconstrictor nasal drops, nasal cavity irrigation using 0.1% Miramistine solution, gargling using the Furacilin solution); forty people (group 3) were administered application of intranasal interferon α2b of 105 IU, it was delivered with a spray into each nasal passage twice a day; 36 people (group 4) were administered an immunotropic drug containing β-D-glucans orally twice a day. The duration of drug administration lasted 7 days. Polymerase chain reaction (PCR) was used to identify the ANP etiological factor. Concentrations of cytokines IL-1β, IL-1ra were estimated using enzyme immunoassay (ELISA) technique. Clinical efficiency was assessed through score approach. The following symptoms were taken into account: general malaise, sore throat, character of nasal discharge, and the difficulty of nasal breathing. The results of the study were analyzed using parametric and nonparametric statistical methods. In 60.0% the nasal secretions of patients revealed RV. The distribution of cytokine concentrations in nasal secretions in group 1 indicated that the concentration of IL-1β was in the range of 20.0-25.0 pg/ml, and the concentration of IL-1ra was about 1250.0-2500.0 pg/ml. Developing ANP stimulated an increase in IL-1β concentration up to 30.0-70.0 pg/ml in nasal secretions of patients without affecting IL-1ra concentrations. On day 7 of treatment, the cytokine concentrations among the patients treated using the immunotropic drugs were the same as in the group of healthy individuals. There were no significant changes in cytokine production on day 7 in the group of patients undergoing the standard treatment. Application of proposed immunobiological medicines to ANP does not result in overproduction of proinflammatory cytokine IL-1β in nasal secretion. This confirms that these drugs are promising in the treating strategy including reduction of the risk of developing complications.

1012. Neutrophil Function Enhanced by Recombinant Interferon-Gamma in Newborns

Background Functional differences exist between neonatal and adult neutrophils. The incidence of infection is higher in preterm infants, and the severity of the immune impairment on the neonatal neutrophils is inversely related to gestational age. In order to recognize and combat life-threatening infections, neonates rely predominantly on the innate immune system.Neutrophils are an essential component of innate immunity, and they are the first responders against bacterial and fungal infections. Sepsis continues to be a prominent cause of neonatal mortality, especially among preterm infants. Recombinant interferon-gamma (IFNγ) effects on the immune system have included the upregulation of TLRs expression and stimulation of phagocytosis. They have been shown to reduce severe infections in children with chronic granulomatous disease. Methods After the protocol was IRB approved, we enrolled term infants in their first 48 hours of life (Table 1). We then obtained free flow whole-blood samples through venipuncture from the cephalic vein. Samples were incubated with and without IFNγ for 24 hours. Isolation of unperturbed neutrophils using immunomagnetics was performed for a final concentration of 1x106/mL. We then assessed the neutrophil-bacterial interaction using fluorescent GFP-Staphylococcus aureus, and quantified neutrophil killing function on a novel assay involving fibrin matrix as a more physiologic and three-dimensional (3D) environment than standard in vitro or culture-based assays. We evaluated normalized progressive ratios, 20μL/80μL, 30μL/70μL, 40μL/60μL of Neutrophil/GFP-S aureus respectively.Table 1 Results On the 20 samples, we observed significant differences demonstrating a considerably enhanced phagocytosis on those samples with the addition of IFNγ(p&lt; 0.0001, Table 2 and Figures 1-3). Conclusion The phagocytic ability of neonatal neutrophils was greatly enhanced by the addition of IFNγ in term infant blood. Ongoing work will determine whether this remains true for preterm-infant neutrophils and will further delineate mechanisms of these differences. We recognized an opportunity for interferon-based immunomodulation in certain situations on this population at high risk for invasive bacterial infections. Disclosures Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Consultant)

Genomic Profiling of a Randomized Trial of Interferon-α versus Hydroxyurea in MPN Reveals Mutation-Specific Responses

Background Although somatic mutations influence the pathogenesis, phenotype, and outcome of myeloproliferative neoplasms (MPN), little is known about their impact on molecular response to cytoreductive treatment. Methods We performed targeted next-generation sequencing (NGS) on 202 pre-treatment samples obtained from patients with MPN enrolled in the DALIAH trial (randomized controlled phase III clinical trial, NCT01387763) and 135 samples obtained after 24 months of therapy with recombinant interferon-alpha (IFNα) or hydroxyurea (HU). The primary aim was to evaluate the association between complete clinicohematologic response (CHR) at 24 months and molecular response through sequential assessment of 120 genes using NGS. Results Among JAK2-mutated patients treated with IFNα, those with CHR had a greater reduction in the JAK2 variant allele frequency (VAF) (median 0.29 to 0.07; p&lt;0.0001) compared with those not achieving CHR (median 0.27 to 0.14; p&lt;0.0001). In contrast, the CALR VAF did not significantly decline in neither those achieving CHR nor those not achieving CHR. Treatment-emergent mutations in DNMT3A were observed more commonly in patients treated with IFNα compared with HU, p=0.04. Furthermore, treatment-emergent DNMT3A-mutations were significantly enriched in IFNα treated patients not attaining CHR, p=0.02. A mutation in TET2, DNMT3A, or ASXL1 was significantly associated with prior stroke (age-adjusted OR=5.29 [95% CI, 1.59-17.54]; p=0.007) as was a mutation in TET2 alone (age-adjusted OR=3.03 [95% CI, 1.03-9.01]; p=0.044). Conclusion At 24 months, we found mutation-specific response patterns to IFNα: (1) JAK2- and CALR-mutated MPN demonstrated distinct molecular responses and (2) DNMT3A-mutated clones/subclones emerged on treatment.

Complex treatment of acute respiratory viral infections with bacterial exacerbation in preschool children

Представлены результаты проспективного сравнительного клинического исследования эффективности и безопасности применения ректальных суппозиториев, содержащих рекомбинантный интерферон альфа-2b в сочетании с антиоксидантами – витаминами Е и С, в комплексной терапии острых респираторных вирусных инфекций среднетяжелого и тяжелого течения с бактериальными осложнениями (пневмония, бронхит, синусит, отит, фаринготонзиллит). Обследованы 60 детей от 1 месяца до 6 лет из II-IV групп здоровья, которые были госпитализированы не позднее третьих (80%) и пятых-шестых (20% больных) суток с момента начала острой респираторно-вирусной инфекции. Из них пациенты с патологией нижних дыхательных путей составили 68,3%; внебольничная пневмония, ассоциированная с ОРВИ, в половине случаев (55,6% и 66,6% соответственно) протекала с синдромом бронхиальной обструкции. Терапевтическая эффективность применения рекомбинантного интерферона альфа-2b в сочетании с антиоксидантами – витаминами Е и С по 150 000 МЕ 2 раза в сутки с интервалом 12 часов в течение 5 дней на фоне стандартной терапии основного заболевания у детей с бактериальными осложнениями острой респираторно-вирусной инфекции проявлялась в виде значимых различий по показателю синдрома бронхиальной обструкции начиная с первого дня терапии и значимого уменьшения симптома кашля и суммарного балла основных клинических симптомов заболевания к четвертому дню терапии по сравнению с группой пациентов, получавших только стандартную терапию респираторного заболевания. В связи с тем, что средняя длительность острой респираторно-вирусной инфекции с осложнениями составила 8 койко-дней (7,8 ± 2,37 и 8,77 ± 2,6 койко-дня соответственно), получение значимо лучших результатов в группе пациентов, применявших рекомбинантный интерферон альфа-2b в сочетании с антиоксидантами – витаминами Е и С, доказывает эффективность данной лечебной схемы терапии. The article presents the results of a prospective comparative clinical study of the efficacy and safety of rectal suppositories containing recombinant interferon alfa-2b in combination with antioxidants vitamins E and C in the complex therapy of acute respiratory viral infections (ARVI) with moderate and severe course with bacterial complications (pneumonia, bronchitis, sinusitis, otitis media, pharyngotonsillitis). The research examined 60 children at the age of 1 month to 6 years from II-IV health status groups, which were hospitalized not later than 3 days after coming down with ARVI (80% of patients) or 5-6 days after coming down with ARVI (20% of patients). 68,3% of patients came with lower respiratory tract impairment; the ARVI-associated community-acquired pneumonia in half the cases (55,6% and 66,6%, respectively) proceeded with bronchial obstruction syndrome. Results: the therapeutic efficacy of recombinant interferon alfa-2b in combination with antioxidants E and C 150 000 ME administration 2 times a day with an interval of 12 hours for 5 days, with underlying routine treatment of primary disease in children with bacterial exacerbation of ARVI, manifested itself in significant difference in bronchial obstruction syndrome indicator starting from the 1st day of treatment, and in significant decrease of cough syndrome and main clinical syndromes total score by the 4th day of treatment, compared to the group of patients treated with a standard ARVI therapy. Due to the fact that the average duration of ARVI disease with complications was 8 bed days (7,80 + 2,37 bed days and 8,77 + 2,60, respectively), the presence of significantly better results in the group of patients who used recombinant interferon alpha-2b in combination with antioxidants vitamins E and C shows the effectiveness of this treatment regimen.

Novel Long-Acting Ropeginterferon Alfa-2b: Pharmacokinetics, Pharmacodynamics, and Safety in a Phase I Clinical Trial

AIM Ropeginterferon alfa-2b is a new site-specific conjugated 40 kDa branched polyethylene-glycol recombinant interferon (IFN). The aim of the study was to determine its safety, pharmacokinetics (PK) and pharmacodynamic (PD). METHODS Ropeginterferon alfa-2b was evaluated first in human in 48 healthy male volunteers after a single dose subcutaneous injection by either 24, 48, 90, 180, 225, 270mcg of the product or 180mcg of marketed pegylated (peg)-IFN alfa-2a. Within each dosing group, 6 subjects received ropeginterferon alfa-2b and 2 subjects received peg-IFN alfa-2a. RESULTS Dose-related increases in ropeginterferon alfa-2b PK parameters (Cmax, AUC, and AUC0-t) were observed over the dose range 24 to 270mcg. The geometric mean values for these PK parameters of ropeginterferon alfa-2b were higher than that of peg-IFN alfa-2a at the 180mcg dose level of 176%, 166%, and 182%, respectively. Mean PD parameters (Emax, Tmax, and AUC0-t) for ropeginterferon alfa-2b increased with dose for both biomarkers neopterin and 2’, 5’-OAS. Ropeginterferon alfa-2b has similar PD profiles as peg-IFN alfa-2a. The treatment related adverse events are similar between the two study drugs, but the overall incidence was numerically lower for ropeginterferon alfa-2b (83%) than peg-IFN alfa-2a (100%) at the 180mcg dose level. CONCLUSIONS Single subcutaneous dose of Ropeginterferon alfa-2b of up to 270mcg is safe and well tolerated. It displays dose related increase in PK and PD parameters, potentially less frequent injection, and better safety profiles. Ropeginterferon alfa-2b is being developed for diseases in which previous peg-IFN use has been limited by side effects.

Assessment of the timeliness of vaccination against pertussis in children of the first year of life and the reasons for the violation of the vaccination schedule

The maximum incidence of pertussis in young children confirms the importance of their timely immunization.The goal is – to study the timeliness of vaccination against whooping cough, causes of violation of the vaccination schedule in young children, the effect of recombinant interferon-a on the post-vaccination period.Materials and methods: the vaccination history and data on the course of the post-vaccination period after immunization with DPT and DaPT vaccines of 469 children at the age of 3–24 months were studied.Results. The analysis showed that 14,9% of the observed children were not vaccinated against whooping cough in a timely manner. Of these: 34,3% had a written refusal to vaccinate (5.1% of the total number of observed children), in 32,8% of cases, the vaccination schedule was violated due to late arrival of parents, 32,9% of children by the start of immunization had medical challenges, and only half of them had justified contraindications. Non-serious side effects associated with immunization were observed in 11.3% of cases, statistically more often with DTP (22,0%) compared with DaPT (5.,5%). General and local reactions, in general, were recorded on DPT (6,9% and 15,1%, respectively) and less often developed with the use of DaPT (1,0% and 4,5%, respectively). Within 1 month after immunization, 16,2% of the observed children had an acute respiratory viral infection of varying severity. Those who did not receive antiviral therapy more often carried the disease in a moderate and severe form, which in all cases led to the postponement of the administration of the second and third doses of the vaccine.Conclusion. To increase the timeliness of vaccination of children against whooping cough, medical professionals should persistently remind parents about the timing of turnout for the next vaccination, when making medical withdrawals, be guided by modern methodological documents and instructions for vaccines. The use of antiviral and immunomodulatory effects of IFN-alpha drugs allows us to comply with the recommended schedule for vaccination of children with a high risk of SARS in the post-vaccination period.