Intergrated associated with Academic Technologies

Deiodinase enzymes are critical for tissue-specific and temporal control of activation or inactivation of thyroid hormones during vertebrate development, including amphibian metamorphosis. We previously screened ToxCast chemicals for inhibitory activity toward human recombinant Type 3 iodothyronine deiodinase enzyme (hDIO3) and subsequently produced Xenopus laevis recombinant dio3 enzyme (Xldio3) with the goals to identify specific chemical inhibitors of Xldio3, to evaluate cross-species sensitivity and explore whether the human assay results are predictive of the amphibian. see more We identified a subset of 356 chemicals screened against hDIO3 to test against Xldio3, initially at a single concentration (200 μM), and further tested 79 in concentration-response mode. Most chemicals had IC50 values lower for hDIO3 than for Xldio3 and many had steep Hill slopes (a potential indication of non-specific inhibition). However, eight of the most potent chemicals are likely specific inhibitors, with IC50 values of 14 μM or less, Hill slopes near -1 and curves not significantly different between species likely due to conservation of catalytically active amino acids. Controlling for assay conditions, human in vitro screening results can be predictive of activity in the amphibian assay. This study lays the groundwork for future studies using recombinant non-mammalian proteins to test cross-species sensitivity to chemicals. DISCLAIMER The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
Avidity is defined as the strength of binding between immunoglobulin G (IgG) and its specific target epitope. IgG of high avidity is established during affinity maturation. Failure to achieve high avidity IgG may result in a lack of protective immunity towards infection and disease. It is known that the interaction between SARS-CoV-2 spike protein and its cellular receptor is driven by high affinity. Therefore, it is predictable that protective antibodies towards SARS-CoV-2 should show high affinity/avidity. AVIDITY AFTER SARS-COV-2 INFECTION Recent findings by several groups demonstrate that the serological response towards infection with SARS-CoV-2 and seasonal coronaviruses is characterized by incomplete avidity maturation, followed by a decline of the serological response. This response might facilitate reinfection, prevent herd immunity and potentially allow repeated cycles of infection. CONSEQUENCES FOR VACCINATION TOWARDS SARS-COV-2 Therefore, the sole focus on antibody titers reached after vaccinatition with SARS-CoV-2 and seasonal coronaviruses is characterized by incomplete avidity maturation, followed by a decline of the serological response. This response might facilitate reinfection, prevent herd immunity and potentially allow repeated cycles of infection. CONSEQUENCES FOR VACCINATION TOWARDS SARS-COV-2 Therefore, the sole focus on antibody titers reached after vaccination towards SARS-CoV-2 might not be sufficient to evaluate the degree of achieved protection. Rather, it is suggested to include avidity determination to optimize vaccination protocols and achieve high avidity IgG directed towards SARS-CoV-2 through vaccination. Avidity determination might also be useful to control for truly protective immunity towards SARS-CoV-2 in individual cases.Zika virus (ZIKV) is a Flavivirus transmitted by Aedes mosquitoes, and was responsible for a worldwide outbreak between 2013 and 2016. However, no ZIKV outbreak has been described in Southeast Asia since 2017. In this study, we report the first microcephaly case with probable ZIKV infection during pregnancy in Lao People's Democratic Republic.
To evaluate the efficacy and safety of pegylated interferon alfa-2b (PEG IFN-α2b) along with the standard of care (SOC) in subjects with moderate COVID-19.
In this phase 2, randomized, open-label study, adult subjects aged ≥18 years with RT-PCR confirmed COVID-19 with moderate symptoms were randomized in a 11 to receive PEG IFN-α2b plus SOC, or SOC alone. The primary endpoint was improvement in clinical status on day 15, measured by the WHO 7-point ordinal scale.
Forty subjects were randomized to PEG IFN-α2b plus SOC (n = 20) and SOC (n = 20). Overall, 19 (95.00%) subjects in PEG IFN-α2b plus SOC had achieved clinical improvement on day 15 compared to 13 (68.42%) subjects in SOC (p < 0.05). Overall, 80% and 95% of subjects in the PEG IFN-α2b plus SOC group had a negative RT-PCR result on day 7 and day 14, respectively, compared to 63% and 68% in the SOC group. Adverse events (AEs) were reported for eleven subjects in the PEG IFN-α2b plus SOC group and eight subjects in the SOC group. All reported AEs were mild.
The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.
The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.
The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI).
We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S).
We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively).