ABSTRACT
Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developing the capacity for immune evasion and resistance to existing vaccines and drugs. To address this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T cell immunity, and rapid production. Synthetic peptide vaccines, which are inexpensive and quick to produce, show low toxicity, and can be selected from the conserved SARS-CoV-2 proteome, are promising candidates. In this study, we evaluated the effectiveness of a synthetic peptide cocktail containing three murine CD4+ T-cell epitopes from the SARS-CoV-2 nonspike proteome and one B-cell epitope from the Omicron BA.1 receptor-binding domain (RBD), along with aluminum phosphate (Al) adjuvant and 5' cytosine-phosphate-guanine 3' oligodeoxynucleotide (CpG-ODN) adjuvant in mice. The peptide cocktail induced good Th1-biased T-cell responses and effective neutralizing-antibody titers against the Omicron BA.1 variant. Additionally, H11-K18-hACE2 transgenic mice were fully protected against lethal challenge with the BA.1 strain, with a 100% survival rate and reduced pulmonary viral load and pathological lesions. Subcutaneous administration was found to be the superior route for synthetic peptide vaccine delivery. Our findings demonstrate the effectiveness of the peptide cocktail in mice, suggesting the feasibility of synthetic peptide vaccines for humans. IMPORTANCE Current vaccines based on production of neutralizing antibodies fail to prevent the infection and transmission of SARS-CoV-2 Omicron and its subvariants. Understanding the critical factors and avoiding the disadvantages of vaccine strategies are essential for developing a safe and effective COVID-19 vaccine, which would include a more effective and durable cellular response, minimal effects of viral mutations, rapid production against emerging variants, and good safety. Peptide-based vaccines are an excellent alternative because they are inexpensive, quick to produce, and very safe. In addition, human leukocyte antigen T-cell epitopes could be targeted at robust T-cell immunity and selected in the conserved region of the SARS-CoV-2 variants. Our study showed that a synthetic SARS-CoV-2-derived peptide cocktail induced full protection against lethal infection with Omicron BA.1 in H11-K18-hACE2 mice for the first time. This could have implications for the development of effective COVID-19 peptide vaccines for humans.
ABSTRACT
The effects of thermally and Fe(II) activated potassium persulfate (PPS) on sludge dewatering performance were compared systematically. Sludge dewaterability was monitored by measuring capillary suction time (CST) and sludge specific resistance to filtration (SRF), and the degradation effect was characterized by chemical oxygen demand (COD), total organic carbon (TOC), ammonia nitrogen (NH4+-N) and extracellular polymeric substances (EPS). The change of extracellular polymer substance (EPS) including soluble, loosely bound and tightly bound EPS (S-EPS, LB-EPS and TB-EPS) with time and PPS dosage was monitored to discuss the oxidation efficiency of thermally and Fe(II) activated PPS. Sludge supernatant was analyzed by three-dimensional fluorescence excitation-emission spectra (3D-EEM) to confirm the protein transformation. The result showed that sludge dewaterability in terms of CST and SRF were enhanced with increasing PPS dosage and condition time of two activated methods. While Fe(II) activated PPS could reduce sludge CST and SRF to preferred values at low PPS dosage and short condition time. Meanwhile, sludge degradation effect was also more obvious. Mechanically, sludge TB-EPS in proteins and polysaccharides converted to SB-EPS was faster with Fe(II) activated PPS. In addition, thermally activated PPS tended to oxidize the protein in the supernatant first.
Subject(s)
Sewage , Water , Extracellular Polymeric Substance Matrix , Ferrous Compounds , Oxidation-ReductionABSTRACT
Electrolysis zero-valent iron activated peroxymonosulfate (EZVI-PMS) was applied to enhance sludge dewaterability and disintegration performance. Sludge dewaterability was characterized by capillary suction time (CST), specific resistance to filtration (SRF), and disintegration performance was explored by measuring sludge DNA content, ammonia nitrogen, chemical oxygen demand (COD), extracellular polymeric substances (EPS) and dissolved organic carbon (DOC). EPS, including soluble EPS (SB-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) were analyzed by three dimensional fluorescence excitation-emission spectrum (3D-EEM) to confirm the proteins' transformation tendency. DOC, protein and polysaccharide in EPSs were quantified to investigate the conditioning mechanism. The results showed that sludge CST and SRF were reduced significantly when the current was 0.2 A and PMS dosage was 130 mg/gDS with the reductions of 43.8% and 74.1%, respectively, and DNA was released from sludge cells to the liquid phase. Mechanically, sludge TB-EPS converted to SB-EPS with DOC in TB-EPS decreasing from 367.0 mg/L to 210 mg/L, while DOC in SB-EPS increased from 44 mg/L to 167.4 mg/L. Besides, the changes of protein and polysaccharide contents in SB-EPS and TB-EPS were similar to DOC, and protein in TB-EPS transformed to other protein-like or organic substances obviously.
