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Human respiratory syncytial virus (HRSV) is a leading cause worldwide of severe respiratory illness in infants and the elderly. The ideal HRSV vaccine should induce a systemic immune response, especially mucosal immunity. In this study, mice were immunized twice with F protein combined with CpG adjuvant to compare the safety and efficacy of 4 immunization routes, including intranasal primed/intramuscular boosted immunization (CpG + F/in+im), intramuscular primed/intranasal boosted immunization (CpG + F/im+in), intramuscular primed/intramuscular boosted immunization (CpG + F/im + im) and intranasal primed/intranasal boosted immunization (CpG + F/in+in). Compared with the control group (CpG/in+im, CpG/im+in, CpG/im + im and CpG/in+in), all 4 immunization routes induced a high titer of neutralizing antibodies and a strong cellular immune response. Mice in the CpG + F/in+in group induced the highest antibody neutralization titer, and IgA antibody in bronchoalveolar lavage fluid (BALF) was the highest. The copy of HRSVs in the lung decreased by approximately 3 log10. As seen from the IgG1/IgG2a and IFN-γ/IL-4-secreting lymphocyte ratios, compared with the mice in the CpG + F/im + im group, mice in the CpG + F/in+in group induced Th1-baised humoral and cellular immune responses and significantly reduced lung pathological injury. In conclusion, among the 4 immunization routes, the safety and efficacy induced by the mice in the CpG + F/in+in group were the best. We can conclude that intranasal immunization is superior to intramuscular immunization using F protein with CpG adjuvant as vaccine candidates.

Background The continuous evolution of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Response System. Sample quality is essential for surveillance quality. Methods To evaluate the RNA degradation of clinical samples, influenza-like illness samples were collected from four sentinel hospitals, and seasonal influenza was tested by real-time reverse transcription polymerase chain reaction and quantified by digital reverse transcription polymerase chain reaction at different time points. Results RNA degradation was observed in the majority of samples eight days after sample collection. A significant and faster rate of RNA content reduction was observed in low viral load samples ( 10 copies/μl), stored at 2 to 8°C for up to eight days. RNase P (RNP) RNA, which is a key indicator to evaluate sample collection quality, was detected. Sample collection quality was uneven in different hospitals. Conclusion Low viral load samples increase the risk of false negatives due to RNA degradation to undetectable levels.

Background: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. Methods: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. Results: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p 80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. Conclusion: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.