Epistemic_Statements  

CORD-19:3c04181700d35b87b9a98c598814442b28ff9abf JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-169 Epistemic_statement denotes Recent advances in the production of recombinant subunit vaccines in Pichia pastoris Recent advances in the production of recombinant subunit vaccines in Pichia pastoris
T2 180-319 Epistemic_statement denotes Recombinant protein subunit vaccines are formulated using defined protein antigens that can be produced in heterologous expression systems.
T3 603-773 Epistemic_statement denotes Codon bias, gene dosage, endoplasmic reticulum protein folding and culture condition are important considerations for improved production of recombinant vaccine antigens.
T4 896-1219 Epistemic_statement denotes P. pastoris has become a highly successful expression system, due to its increasing popularity, which can be attributed to several factors such as high growth rate, the ease of genetic manipulation, high yield expression of heterologous proteins and the capability of performing eukaryotic post-translational modifications.
T5 1338-1495 Epistemic_statement denotes 3 P. pastoris usually produces higher yield of recombinant proteins and is less demanding in terms of time and effort relative to complex eukaryotic systems.
T6 1610-1732 Epistemic_statement denotes Vaccines against viruses can be divided into 3 main categories: live attenuated, inactivated/killed, and subunit vaccines.
T7 1874-1983 Epistemic_statement denotes 6 The replication of live attenuated viruses should be sufficiently restricted to avoid pathological effects.
T8 1984-2175 Epistemic_statement denotes Although live attenuated vaccines could induce strong and long-lasting immune responses, they might reverse to virulent wild-type strains that cause diseases in immunocompromised individuals.
T9 2293-2550 Epistemic_statement denotes 8 Inactivated/ killed vaccines may present production problems at commercial scale, in terms of growth of the virus to sufficiently high titers of economical yield, as well as hazardous containment issues for large scale growth of non-attenuated live virus.
T10 2551-2695 Epistemic_statement denotes 9 Recombinant protein subunit vaccines are composed of at least 1 type of viral antigen that can be produced in heterologous expression systems.
T11 2817-2954 Epistemic_statement denotes In addition, recombinant protein subunit vaccines can be scaled up in a more cost-effective manner compared with other types of vaccines.
T12 3135-3230 Epistemic_statement denotes 10 Subunit vaccines must be efficacious, safe, and can be easily scaled up for mass production.
T13 3360-3594 Epistemic_statement denotes 11 P. pastoris-produced biopharmaceuticals or industrial enzymes have been approved by the United States Food and Drug Administration (FDA), indicating that the P. pastoris system is widely accepted as safe and suitable for human use.
T14 4630-4743 Epistemic_statement denotes 17 Mut ¡ strains are unable to grow on methanol as the sole carbon source due to the knock-out of both AOX genes.
T15 4744-4977 Epistemic_statement denotes 18 The success of P. pastoris in the production of recombinant proteins is directly linked to the very strong and inducible promoter of the gene encoding the first enzyme of the methanol utilization pathway, alcohol oxidase 1 (AOX1).
T16 5410-5594 Epistemic_statement denotes Alternative inducible or constitutive promoters, which can be induced without methanol but still reach high expression levels, have been used in the production of recombinant proteins.
T17 5922-6078 Epistemic_statement denotes 24 Constitutive expression eases process handling, avoids the use of potentially hazardous inducer and provides continuous transcription of the target gene.
T18 6079-6293 Epistemic_statement denotes The glyceraldehyde-3-phosphate promoter (P GAP ) provides constitutive expression of foreign proteins on glycerol, glucose and methanol media, which can reach the same expression levels as methanol-induced P AOX1 .
T19 6653-6781 Epistemic_statement denotes 28 To obtain high yield of foreign proteins, the optimal clone containing multiple copies of the target gene must be determined.
T20 6782-6896 Epistemic_statement denotes Copy number can be assessed through colony screening using enhanced concentrations of antibiotic or real-time PCR.
T21 7511-7597 Epistemic_statement denotes 14 Foreign protein expression in P. pastoris can either be intracellular or secretory.
T22 7940-8075 Epistemic_statement denotes 34 The a-MF signal sequence has been proven to be the most effective in directing protein through the secretory pathway in P. pastoris.
T23 8076-8238 Epistemic_statement denotes It has been reported that using a-MF as the signal peptide can lead to the production of higher amounts of a foreign protein than using its native signal peptide.
T24 8677-8871 Epistemic_statement denotes Although these vaccine formulations have shown success and some diseases such as polio have been eradicated from most parts of the world, many issues still remain associated with these vaccines.
T25 8872-8967 Epistemic_statement denotes For example, these vaccines are not always effective, and are needed to maintain cooling chain.
T26 8968-9038 Epistemic_statement denotes In immunocompromised people, live vaccines may lead to severe disease.
T27 9039-9163 Epistemic_statement denotes 36 Costs related to the production and administration makes these vaccines difficult to use for mass immunization of people.
T28 9164-9273 Epistemic_statement denotes 37 Therefore, there is an urgent need to develop more effective subunit vaccines against infectious diseases.
T29 9972-10065 Epistemic_statement denotes An ideal subunit vaccine should be safe, stable and immunogenic in all immunized individuals.
T30 10066-10193 Epistemic_statement denotes 41 The manufacture, purification and characterization should be efficient, and be inexpensive to enable widespread vaccine use.
T31 10694-10871 Epistemic_statement denotes 45, 46 Some recombinant viral antigens can spontaneously assemble into virus-like particles (VLPs) which are multiprotein structures without the incorporation of a viral genome.
T32 10872-11008 Epistemic_statement denotes 47, 48 VLPs is a potentially safe subunit vaccine that can induce immune responses similar to those prompted by natural viral infection.
T33 12145-12327 Epistemic_statement denotes During this time, the antigen composition of the target pathogen might be adjusted, and vaccine dosage can also be increased due to lacking the long-term immunity after immunization.
T34 12328-12431 Epistemic_statement denotes 55 The antigen that can stimulate protective immune responses is usually chosen as a vaccine candidate.
T35 12551-12627 Epistemic_statement denotes However, animal experiments are still the main focus of preclinical studies.
T36 12766-12890 Epistemic_statement denotes 57 Pharmacological and toxicological effects of vaccine candidates should be assessed before initiation of clinical studies.
T37 13409-13648 Epistemic_statement denotes 39, 59, 60 Although E. coli has many advantages as a production system, generating recombinant proteins in this system can often result in inclusion body formation or low yields of foreign proteins lacking post-translational modifications.
T38 13851-13958 Epistemic_statement denotes Among eukaryotic microbes systems, P. pastoris is a promising platform to produce various foreign proteins.
T39 14509-14723 Epistemic_statement denotes EBV is a ubiquitous human herpesvirus that is associated with the development of various malignancies such as nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), Hodgkin lymphoma (HL) and Burkitt lymphoma (BL).
T40 14811-14937 Epistemic_statement denotes The secretory form of truncated gp350 (gp350 1-443 , codons 1-443) has the potential to be developed into EBV subunit vaccine.
T41 15062-15161 Epistemic_statement denotes 64 EBV nuclear antigen 1 (EBNA1) is thought to be a promising antigen for EBV therapeutic vaccines.
T42 15549-15636 Epistemic_statement denotes However, these results were not effective enough to use it as an EBV vaccine candidate.
T43 15827-15948 Epistemic_statement denotes 67 Envelope domain-III (EDIII) antigen of DENV-3 has garnered much attention as a promising vaccine candidate for dengue.
T44 16018-16197 Epistemic_statement denotes 68 The result suggested that casamino acids supplementation facilitated overexpressing P. pastoris cells to secrete more EDIII by reducing the proportion retained intracellularly.
T45 16198-16262 Epistemic_statement denotes The purified EDIII antigen could induce neutralizing antibodies.
T46 16263-16468 Epistemic_statement denotes The strategy described in this study enabled fulfilling the mounting demand for recombinant EDIII as well as laid direction to future studies on secretory expression of recombinant proteins in P. pastoris.
T47 17084-17235 Epistemic_statement denotes P. pastorisproduced recombinant E protein could stimulate immune responses that were capable of mediating significant protection against JEV infection.
T48 17236-17333 Epistemic_statement denotes This study might provide helpful information for the development of subunit vaccines against JEV.
T49 17544-17627 Epistemic_statement denotes 73 The recombinant VP1 could elicit protective immune responses in vaccinated mice.
T50 17628-17719 Epistemic_statement denotes The P. pastoris-expressed VP1 is a promising EV71 vaccine candidate for industrial purpose.
T51 17720-17876 Epistemic_statement denotes The successful expression of these viral antigens highlighted the potential of P. pastoris in developing safe, efficacious, and affordable subunit vaccines.
T52 18531-18690 Epistemic_statement denotes Therefore, this is a great need for the development of an alternative system for the production of HPV vaccines that can be provided by public health programs.
T53 18947-19012 Epistemic_statement denotes Coxsackievirus A16 (CA16) can cause HFMD in infants and children.
T54 19013-19165 Epistemic_statement denotes 78 P. pastoris-derived CA16 VLPs could induce high-titer serum antibodies and confer complete protection against CA16 lethal challenge in neonatal mice.
T55 19166-19352 Epistemic_statement denotes 79 The yield of CA16 VLPs was 8.3 mg/ L. However, the CA16 VLPs yield in P. pastoris could be further improved via optimization of regulatory elements or high-density yeast fermentation.
T56 19598-19777 Epistemic_statement denotes The EV71 VLPs could induce neutralizing antibodies against both homologous and heterologous EV71 strains, and conferred protection against lethal virus infection in neonatal mice.
T57 20096-20235 Epistemic_statement denotes P. pastoris-derived HBsAg-based VLPs could elicit significantly high HBsAg-specific IgG titers as well as strong cellular immune responses.
T58 20236-20367 Epistemic_statement denotes The results indicated that HBsAg-based VLPs had the potential as a superior vaccine to currently licensed HBV vaccine (Engerix-B®).
T59 20368-20559 Epistemic_statement denotes These results demonstrated that P. pastoris-produced VLPs represented promising vaccine candidates with proven preclinical efficacy and desirable traits for manufacturing at industrial scale.
T60 21418-21579 Epistemic_statement denotes 84 Not all recombinant proteins are efficiently secreted into the medium, and endoplasmic reticulum (ER) retention during high-level production can be a problem.
T61 21706-22001 Epistemic_statement denotes When the recombinant protein fails to fold into its native state or protein expression exceeds the folding capacity of the ER, the unfolded or aggregated proteins may start to accumulate in the ER, thus triggering the unfolded protein response (UPR) and ER-associated degradation (ERAD) pathway.
T62 22292-22434 Epistemic_statement denotes 87,88 ER stress and protein folding can affect the redox state of ER and the cytosolic redox balance, which have an impact on protein folding.
T63 22435-22619 Epistemic_statement denotes 89 By altering the levels of redox active enzymes such as the antioxidant transcription factor Yap1 or glutathione peroxidase (GPX), the yield of the foreign protein could be improved.
T64 22932-23200 Epistemic_statement denotes Multiple approaches have been implemented to solve this problem, such as addition of protease inhibitors, peptone, casamino acids or specific amino acids, optimization of cultivation conditions (pH and temperature) and medium composition (nitrogen and carbon sources).
T65 23261-23367 Epistemic_statement denotes Genetic manipulation of the host proteases can efficiently reduce the degradation of recombinant proteins.
T66 23943-24065 Epistemic_statement denotes 96 The optimization of culture condition and induction protocol are also essential to increase recombinant protein yields.
T67 24066-24326 Epistemic_statement denotes 97 Various condition and induction parameters including media composition, temperature, pH, methanol concentration and induction time should be considered in designing an optimal production system to achieve high yield of the desired protein in an active form.
T68 24485-24596 Epistemic_statement denotes High purity of recombinant vaccine candidates with less contaminating protein could be obtained in P. pastoris.
T69 25043-25233 Epistemic_statement denotes Thus, it can be assumed that the biopharmaceutical application of P. pastoris system will rapidly increase, adopting a place among the top 3 production systems besides E. coli and CHO cells.
T70 26193-26243 Epistemic_statement denotes No potential conflicts of interest were disclosed.