Search

BACKGROUND. The Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins. METHOD. We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 [micro]g UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 [micro]g of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 [micro]g of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose. RESULTS. No vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long- lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs. CONCLUSION. UB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines. TRIAL REGISTRATION. ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742. FUNDING. UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare., Introduction The combined effects of SARS-CoV-2 neutralization-escape variants with high transmissibility by asymptomatic persons (1, 2) and breakthrough infections due to waning immunity of COVID-19 vaccines (3-5) continue to cost [...]

Japanese encephalitis virus (JEV), a mosquitoborne Vflavivirus, causes Japanese encephalitis (JE). This virus has been reported in Southeast Asia and Western Pacific regions since it emerged during the 1870s in [...]

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown [...]

During 2012–2017, a total of 1,144 highly pathogenic avian influenza (HPAI) H5 outbreaks were reported in Taiwan. We conjectured the current 3‐km radius of the post‐outbreak containment policy could fail to effectively alleviate the current ongoing epidemics of HPAI H5 in Taiwan. The high intensity of localized transmission of HPAI H5 at certain focal hotspots was identified to follow the spatial distribution of poultry‐raising locations through our hotspot analyses on the HPAI H5 outbreak locations from 2015 to 2017. We then applied 3‐, 5‐ and 7‐km circular buffer zones to 15,444 registered poultry‐raising locations to inspect the characteristics of the poultry‐raising neighbourhood. Three spatial regression models using Bayesian inference were established to infer the risks attributable to poultry‐raising characteristics in the corresponding buffer areas. The different buffer radii were treated as a sensitivity analysis of the influential range of neighbouring farms on the HPAI H5 outbreak occurrence, so as to evaluate the effective radius for post‐outbreak containment. Evidence showed that the risks of outbreak occurrence were associated with increasing numbers of poultry‐raising locations in both 3‐km (relative risk [RR] 1.005, 95% confidence interval [CI] 1.002–1.008) and 5‐km buffer areas (RR 1.005, 95% CI 1.004–1.007), whereas in the 7‐km buffer model, no association between densely populated locations and increasing risks of outbreaks was observed (RR 1.000, 95% CI 0.999–1.001). Therefore, an extension to a 7‐km radius for the post‐outbreak containment policy (rather than a 3‐km radius as in the current policy) is recommended to effectively mitigate further spreading of HPAI H5 outbreaks among neighbouring farms. Overall, we demonstrated that the densely populated locations with multiple poultry species raised in proximity as defined with 3‐, 5‐ and 7‐km buffer areas facilitated H5 HPAI outbreak diffusion and shaped the scale of HPAI H5 epidemics in Taiwan. [ABSTRACT FROM AUTHOR]

Abstract Background Despite intensive vector control efforts, dengue epidemics continue to occur throughout Southeast Asia in multi-annual cycles. Weather is considered an important factor in these cycles, but the extent to which the El Niño-Southern Oscillation (ENSO) is a driving force behind dengue epidemics remains unclear. Methods We examined the temporal relationship between El Niño and the occurrence of dengue epidemics, and constructed Poisson autoregressive models for incidences of dengue cases. Global ENSO records, dengue surveillance data, and local meteorological data in two geographically diverse regions in Thailand (the tropical southern coastal region and the northern inland mountainous region) were analyzed. Results The strength of El Niño was consistently a predictor for the occurrence of dengue epidemics throughout time lags from 1 to 11 months in the two selected regions of Thailand. Up to 22% (in 8 northern inland mountainous provinces) and 15% (in 5 southern tropical coastal provinces) of the variation in the monthly incidence of dengue cases were attributable to global ENSO cycles. Province-level predictive models were fitted using 1996-2004 data and validated with out-of-fit data from 2005. The multivariate ENSO index was an independent predictor in 10 of the 13 studied provinces. Conclusion El Niño is one of the important driving forces for dengue epidemics across the geographically diverse regions of Thailand; however, spatial heterogeneity in the effect exists. The effects of El Niño should be taken into account in future epidemic forecasting for public health preparedness.

To the Editor: The rapid spreading of dengue viruses has led to increasing incidence rates of dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) worldwide in [...]