73 results about "Specific igg" patented technology

The invention discloses a chicken infectious anemia virus subunit vaccine, and belongs to the technical field of animal disease vaccines. The invention provides a chicken infectious anemia virus subunit vaccine. Active ingredients of the chicken infectious anemia virus subunit vaccine are recombinant fusion protein of chicken infectious anemia virus VP1 protein B cell epitope and salmonella typhimurium flagellin. The B cell epitope of the chicken infectious anemia virus VP1 protein is obtained by connecting B cell antigen epitopes contained in the chicken infectious anemia virus VP1 protein through a connecting peptide. The salmonella typhimurium flagellin is obtained by deleting a hypervariable region of the salmonella typhimurium flagellin FliC. The fusion expression protein provided by the invention can induce generation of a specific IgG antibody after one-day-old SPF chicken, and after immunization for 28 days, immunized chicken flocks can resist challenge of chicken infectious anemia virus virulent strains, and 70% of challenge chicken flocks are protected without disease attack. The invention has great potential for clinical prevention and control of chicken infectious anemia virus infection.

The present application provides an RNA encoding a varicella-zoster (VZV) glycoprotein E (gE) or a variant thereof, the RNA comprising a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity with the nucleotide sequence represented by any one of SEQ ID NO: 11-18. The eight mRNAs provided by the invention can translate in cells, the expression level of the generated VZV gE protein is high, and the mRNAs can induce a mouse to generate a high-titer gE specific IgG antibody in a manner of intramuscular injection into the body of the mouse through a preparation formed by encapsulating the lipidosome nanoparticles.

The present disclosure reveals a process for the determination of a risk for the development of cardiovascular disease (CVD) in the future from quantitative analysis of four specific IgG N-glycans isolated from a blood sample of examined human subjects. Said four specific glycans were found to be significant diagnostic markers by statistical analysis of the results obtained from previously performed clinical trials that revealed the variation of quantitative IgG glycans content in the blood plasma in a cohort of normal subjects, versus, those who experienced CVD clinical manifestations. From this analysis, a new numerical model was developed which enables the calculation of the CVD risk parameter (CVDR). The numerical value for CVDR obtained after the inclusion of the result of said four key glycans, obtained from the blood analysis, gives an assessment of the eventual CVD development in the examined subject in the future.

The invention discloses a vaccine composition and a preparation method thereof, the vaccine composition comprises a first component and a second component, the first component is a recombinant protein antigen, the second component is an oil-in-water composite adjuvant, and the oil-in-water composite adjuvant comprises a water phase, an oil phase, an emulsifier, a Toll-like receptor stimulant and / or an STING stimulant. The vaccine composition provided by the invention can stimulate a body to generate a high-level specific IgG antibody and a neutralizing antibody, and has a good cellular immune effect at the same time. The second component provided by the invention is simple in preparation process, low in cost, stable in dosage form, easy to store and good in immune effect, and has a wide application prospect in vaccine or drug development.

The present invention relates to the technical field of nanomaterials for vaccines, and particularly relates to a sepiolite in-situ grown nanozyme, a preparation method thereof and an application thereof. The preparation method is to mix ferric chloride, ethylene glycol and sodium acetate to form a suspension, and then mix sepiolite with the suspension, and react at a temperature of 180-200 °C to obtain a black precipitate. After washing and drying, sepiolite in-situ grown nanozyme is obtained. The sepiolite nanozyme realizes the in-situ growth of iron-based nanozyme on the surface of sepiolite rod-like nanostructures under hydrothermal conditions, significantly enhancing the peroxidase activity. After Sep@IONzyme is connected with inactivated influenza virus, the complex forms an appropriate positive charge distribution, enhancing the adhesion ability of the antigen to nasal mucosa. Immunizing mice with it as a nasal drop vaccine significantly improves the levels of respiratory mucosal specific sIgA antibody and serum specific IgG antibody, and can completely protect against the lethal attack of influenza virus.

The invention discloses a bivalent subunit vaccine for preventing infection of haemophilus parasuis and porcine circovirus type 2. A core antigen combination of the vaccine comprises at least one antigen protein from haemophilus parasuis, and the antigen protein is selected from Ferrin, OppA and Hem-SAP and is combined with a porcine circovirus type 2 Cap protein. Wherein the NCBI (National Center of Biotechnology Information) login number of the Ferrin, the NCBI login number of the OppA and the NCBI login number of the Hem-SAP are WP160414389.1, ACL32731.1 and WP035493594.1 respectively. The antigen protein is subjected to codon optimization, is expressed and purified through a prokaryotic expression system, and is emulsified with ISA201 or a Freund's adjuvant to prepare the vaccine. Animal experiments prove that the vaccine can excite high-level antigen specificity IgG, cell factors IFN-gamma and white IL-4 in an immune animal body, namely, specific Th1 and Th2 type immune responses are generated. The vaccine can generate an immune protection rate of up to 80% when attacked by a serum type 5 haemophilus parasuis virulent strain, and generates an effective antibody response to the porcine circovirus type 2. The vaccine provided by the invention has the advantages of definite components, good safety and strong immune protection force.

The present invention discloses a subunit vaccine against chicken infectious anemia virus, belonging to the technical field of animal disease vaccines. The present invention provides a subunit vaccine against chicken infectious anemia virus, and the active ingredient is a recombinant fusion protein of the B cell epitope of chicken infectious anemia virus VP1 protein and Salmonella typhimurium flagellin. The B cell epitope of chicken infectious anemia virus VP1 protein is obtained by connecting the B cell antigen epitopes contained in chicken infectious anemia virus VP1 protein through a linker peptide. The Salmonella typhimurium flagellin is obtained by deleting the hypervariable region of Salmonella typhimurium flagellin FliC. After the fusion expression protein of the present invention is administered to 1-day-old SPF chickens, it can induce the production of specific IgG antibodies, and after 28 days of immunization, the immunized chicken flock can resist the challenge of the virulent strain of chicken infectious anemia virus, and 70% of the challenged chicken flock is protected from disease. The present invention has great potential for clinical prevention and control of chicken infectious anemia virus infection.

The invention provides a novel vaccine adjuvant and application of the novel vaccine adjuvant in preparation of the vaccine adjuvant. The BCG-PSN and vaccine induced RBD specific IgG antibody and neutralizing antibody level are equivalent to those of an aluminum adjuvant, the BCG-PSN and vaccine induce Th1 biased T cell reaction, the induced T cell response level is obviously higher than that of the aluminum adjuvant, and K18-hACE2 mice are protected from being affected by Delta variant induced lung lesions. As a vaccine adjuvant, BCG-PSN has wide compatibility and safety, and has no toxic or side effect.

The invention relates to the technical field of detection kits, in particular to a milk specificity IgG antibody detection kit which comprises a detection kit body, a storage hole is formed in the bottom end of the detection kit body, the top end of the storage hole is communicated with a discharging cavity, and a feeding pipe fixedly penetrates through the middle of the side face of the detection kit body; the feeding pipe injects a sample solution into the discharging cavity, an extended cleaning mechanism is arranged on the inner wall of the storage hole, the top end of the discharging cavity is communicated with a detection cavity, and a cleaning mechanism, a sampling mechanism and a rotary detection mechanism are arranged on the inner wall of the detection cavity. The extended cleaning mechanism comprises a storage column arranged on the inner wall of the storage hole; the device can ensure that the cleaning scraping plate is continuously and tightly attached to the inner wall of the discharging cavity, the scraping efficiency is guaranteed, the cleaning quality is improved, the cleaning scraping plate can be stored and hidden after cleaning is completed, deformation caused by collision with a sampling rod during sampling is avoided, and the cleaning performance of the cleaning scraping plate is maintained.

The invention relates to an adjuvant composition and application thereof in preparation of an antiviral vaccine, and provides a novel adjuvant composition which can induce an organism to generate a remarkable high-titer specific IgG antibody and enhance humoral immunity, and particularly has a good application prospect for development of the antiviral vaccine.

The invention discloses a recombinant virus vector, a vesicular stomatitis-yellow rice chimeric virus and application of the vesicular stomatitis-yellow rice chimeric virus. The recombinant virus vector is a recombinant vector containing an expression cassette of a vesicular stomatitis-yellow rice chimeric genome; the expression cassette comprises a T7 promoter, a coding sequence of a vesicular stomatitis virus N protein, a coding sequence of a vesicular stomatitis virus P protein, a coding sequence of a vesicular stomatitis virus M protein, a coding sequence of a yellow virus F protein and a coding sequence of a vesicular stomatitis virus L protein which are connected in sequence. The replication-deficient recombinant virus for chimeric expression of the LayV F protein is constructed on the basis of the VSV vector, the safety is good, the immunogenicity is good, a high-titer specific IgG antibody and a neutralizing antibody aiming at LayV can be induced to be generated through intramuscular or subcutaneous injection, a new technical choice is provided for preventing or blocking LayV infection, and the replication-deficient recombinant virus has important use and popularization values.

The invention relates to an adjuvant composition and application thereof in preparation of a varicella vaccine, and provides a novel adjuvant composition which can induce an organism to generate a remarkable high-titer specific IgG antibody, enhance humoral immunity and induce strong cellular immunity, and particularly has a good application prospect for development of the varicella vaccine.

The invention belongs to the technical field of immunology, and particularly discloses application of 2 ', 3'-cGAMP in preparation of a medicine for enhancing chicken pox-herpes zoster virus vaccine immune response. The 2 ', 3'-cGAMP combined varicella-zoster virus vaccine disclosed by the invention can improve the level of a specific IgG antibody, enhance the cellular immune response intensity of a gE antigen and improve the secretion amount of IFN-gamma and IL-2, so that the immune response of the varicella-zoster virus vaccine is enhanced, the immunoprophylaxis effect is enhanced, and the 2 ', 3'-cGAMP combined varicella-zoster virus vaccine adjuvant can be used for preparing a vaccine adjuvant for treating the varicella-zoster virus. Good application prospects are realized.

The application discloses a HtsA-SLOdm fusion protein and application thereof in preparation of a group A streptococcus vaccine. The HtsA-SLOdm fusion protein is obtained by fusing and recombining a heme transport lipoprotein (HtsA) and a streptolysin protein containing a double-mutation site (SLOdm), can induce production of HtsA protein and SLOdm protein specific IgG antibodies in serum, has strong immunogenicity, can induce high-level IgG1 and IgG2a antibody titers, and the humoral immune response in inducing production of SLOdm protein specific IgG antibodies in serum is stronger than that of a single protein. In addition, the HtsA-SLOdm fusion protein can promote skin wound healing of mice, reduce bacterial content and inflammatory response at a skin infection site of the mice, accelerate wound healing, has almost no hemolytic activity, has high safety, and can be used for preparing a group A streptococcus vaccine.

The invention discloses an immunologic adjuvant containing paris polyphylla glucomannan for the first time, and belongs to the technical field of biological medicines. The immunologic adjuvant containing the paris polyphylla glucomannan can promote the phagocytic function of macrophages, promote the secretion of NO and TNF-alpha, promote the maturation of dendritic cells, up-regulate the expression quantity of CD40, CD86 and MHCII, and promote the secretion of TNF-alpha, IL-6 and IL-12. In-vivo experiments show that the immunologic adjuvant containing the paris polyphylla glucomannan can significantly improve the antigen-specific IgG, IgG1 and IgG2a antibody levels, induce Th1 and Th2 type immune responses at the same time, increase the proportion of CD3 + and CD3 + and CD4 + cells in splenic lymphocytes and enhance humoral immunity and cellular immunity levels at the same time. The paris polyphylla gulcomannan in the immunologic adjuvant is obtained by extracting and purifying paris polyphylla plants of alaginaceae, the weight-average molecular weight of the paris polyphylla gulcomannan is 50-800 kDa, monosaccharide composition of the paris polyphylla gulcomannan is mannose and glucose, the ratio of the mannose to the glucose is (10: 1)-(20: 1), and the second site or the third site of the mannose is substituted by acetyl. The invention further discloses a preparation method of the immunologic adjuvant containing the paris polyphylla glucomannan and application of the immunologic adjuvant containing the paris polyphylla glucomannan to preparation of a vaccine preparation or a vaccine composition.

Provided are an RSV F protein mutant, and a preparation method therefor and a use thereof. Provided is a mutant protein, the mutant protein being in the form of a monomer or a trimer, wherein the trimer is formed by three monomeric mutant proteins; the monomeric mutant protein is a fusion protein comprising a first polypeptide element derived from an RSV F protein and a trimerization domain element; in the first polypeptide element, a Pep27 fragment of the RSV F protein is replaced with a linker sequence; and the monomeric and trimeric mutant proteins are both bound by an antibody that specifically recognizes RSV pre-F. The mutant protein can stably remain in a pre-fusion state, can induce the production of specific IgG antibodies and neutralizing antibodies, has excellent immunogenicity, and can be used for the development of RSV vaccines.

An agent including a glycan-specific IgG antibody moiety, a cellular receptor binding moiety which binds to hepatocytes or other degrading cells through asialoglycoprotein (ASGPR) receptors of hepatocytes or other cell receptors which are on the surface degrading cells in a patient or subject, and optionally, a linker moiety connecting the glycan-specific IgG antibody moiety and the cellular receptor binding moiety.

The invention relates to the field of biology, in particular to a duck TRPA1 protein extra-membrane part polyclonal antibody as well as a preparation method and application of the duck TRPA1 protein extra-membrane part polyclonal antibody. The invention provides a duck TRPA1 protein out-of-membrane part polyclonal antibody prepared from TRPA1 recombinant protein and a preparation method of the duck TRPA1 protein out-of-membrane part polyclonal antibody, the titer of the duck TRPA1 protein out-of-membrane part polyclonal antibody is greater than or equal to 1: 256000, and the duck TRPA1 protein out-of-membrane part polyclonal antibody is strong in specificity. The TRPA1 extracellular region (103bp-1051bp) is accurately selected through bioinformatics analysis, so that the expression difficulty caused by a hydrophobic structure of a transmembrane region is avoided, and the target functional epitope of the antibody is ensured; protein aggregation is reduced by utilizing stepped renaturation, and a high-purity antigen is obtained by matching with molecular sieve chromatography; an antigen is coupled with an NHS-active HP column, specific IgG is efficiently captured through a one-step method, and serum impure protein is removed.

The application discloses a bovine parainfluenza virus 3A and 3C type polyepitope antigen peptide, a complex thereof and application. The polyepitope antigen peptides BPMEV-3A and BPMEV-3C have amino acid sequences as shown in SEQ ID NO:1 and SEQ ID NO:3 respectively, and are connected by screening CTL epitopes, HTL epitopes and B cell epitopes from HN and F proteins of BPIV-3A and BPIV-3C strains. Animal immunization tests show that the antigen peptide and the complex thereof can effectively stimulate the body to produce specific IgG antibodies and neutralizing antibodies, induce Th1 type cellular immune response, and effectively eliminate viruses and reduce lung tissue lesions, and show good immunogenicity and protection effect. The application provides an efficient and safe vaccine candidate for prevention and control of BPIV-3, and has a good application prospect.

The present invention relates to an immunoassay for the detection of Borrelia specific IgG, IgM and IgG / IgM antibodies in biological samples suspected of Lyme infection. The immunoassay can be performed via a standard immunoassay format or on an automated platform. In various embodiments, the immunoassay uses one or more Borrelia specific chimeric peptides VlsE-FlaB (designated pFlaB-mV), VlsE-ErpP (designated pErp59-mV), VlsE-P35 (designated pP35-mV) alone or in combination with one or more outer surface protein C (Osp C) types B or I, p58 and DbpA. Other aspects of the invention provide antigen / substrate combinations and compositions comprising combinations of the disclosed peptides and / or proteins for use in the immunoassays described herein.

The invention belongs to the technical field of biomedicine, and particularly relates to a novel small broad-spectrum vaccine immunogenic protein of coronavirus (SARS-CoV-2) and application of the novel small broad-spectrum vaccine immunogenic protein. The two proteins BLEP-1 and BLEP-2 have good immunogenicity, after the two proteins are matched with a Freund's adjuvant, a mouse can be induced to generate a high-titer anti-Wuhan-Hu-1 virus strain / Octhrough variant S protein specific IgG antibody, SARS-CoV-2Wuhan-Hu-1 strain S protein mediated cell-cell fusion can be effectively inhibited, and the effect of the BLEP-2 is superior to that of the BLEP-1. The amino acid sequences of the protein BLEP-1 and the protein BLEP-2 are respectively as shown in SEQ ID NO. 1 and SEQ ID NO. 2. The two candidate vaccines designed by the invention can induce an organism to generate specific Th1 / Th2 mixed immune response aiming at a Wuhan-Hu-1 virus strain and an Omicro variant strain, and have the potential of becoming a novel small broad-spectrum vaccine candidate antigen of coronavirus (SARS-CoV-2), and the design concept can provide a new scheme for the design of a vaccine candidate immunogen of a highly mutant virus.

The present application belongs to the field of biomedical technology, and more particularly relates to the application of Periplaneta americana polypeptide HFDT1 as an immune adjuvant in the preparation of a brucellosis vaccine. The present application uses Brucella OMP10, BP26 and L7 / L12 proteins in combination with HFDT1 to induce mice to produce higher titers of anti-OMP10, BP26 and L7 / L12 protein specific IgG antibodies, and the titers increase with the increase in the number of immunizations, while promoting the body to produce mixed Th1 / Th2 type cellular immune responses and stimulating the proliferation and differentiation of mouse spleen T and B cells, and also facilitating mass production. The Periplaneta americana polypeptide HFDT1 described in the present application is obtained by convenient mass synthesis, and can be used as a novel small molecule immune adjuvant to enhance specific immune responses of the body.

The invention provides polynucleotide for coding an RSV (Respiratory Syndrome Virus) pre-fusion F protein and application of the polynucleotide in an mRNA (Messenger Ribonucleic Acid) vaccine. The sequence of the polynucleotide is as shown in SEQ ID No: 1. Experiments prove that the antigen-specific IgG titer of the polynucleotide, the vaccine and the pharmaceutical composition provided by the invention is 2-4 times that of an unoptimized sequence, so that more efficient expression of target protein in vivo is prompted, and meanwhile, the geometric mean titer value of a neutralizing antibody is also higher than that of the unoptimized sequence, so that good immunogenicity is prompted. The GMT value and the antigen specificity IFN-gamma, IL-5 and IL-17A levels of the neutralizing antibody generated by induction of the RSV mRNA vaccine provided by the invention are obviously higher than those of a control group in the prior art, so that the RSV mRNA vaccine has excellent application prospects.

The invention relates to the technical field of biology, in particular to a method for detecting a varicella-zoster virus gE protein specific IgG antibody in human serum by a high-sensitivity ELISA (Enzyme-Linked Immunosorbent Assay) method.A recombinant VZV-gE protein is adopted to coat an elisa plate, a self-established indirect ELISA method is adopted, and the specific IgG antibody of the varicella-zoster virus gE protein in the human serum is detected by screening the coating concentration, the closing condition, the incubation time, the secondary antibody concentration and the like. The method for detecting the concentration of the VZV-gE protein IgG antibody in the human serum is successfully established; then the positive mixed human serum is calibrated by using the method and an NIBSC international standard substance (NIBSC code: W1044), and the calibrated positive mixed serum is used as an enterprise standard substance for determining the concentration of a VZV-gE protein specific IgG antibody in the human serum; in this way, the technical problem that in the prior art, a detection method for the varicella-zoster virus gE protein specific IgG antibody in human serum cannot meet the requirements for high sensitivity, excellent specificity, high flux and excellent reproducibility at the same time is solved.

This invention relates to the field of biomedical technology, specifically disclosing a three-component recombinant subunit vaccine composition for Mycoplasma pneumoniae and its application. The vaccine composition comprises key antigenic proteins of Mycoplasma pneumoniae (MP): P1 protein, P40 / 90 protein, and an E132A attenuated mutant of community-acquired respiratory distress syndrome (CARDS) toxin (CARDS-Mut), optionally combined with Al(OH)3 single adjuvant or Al(OH)3+CPG double adjuvant. The recombinant protein was successfully purified using a prokaryotic expression system, and validated in a mouse model. The vaccine induces high-titer specific IgG antibodies, significantly alleviates lung tissue pathological damage, reduces bacterial load, and inhibits inflammatory factor secretion after challenge, with good safety. This invention solves the problem of high toxicity of CARDS toxin, providing an efficient and safe vaccine strategy for the prevention and control of MP infection.

The invention discloses a coupling protein as well as a preparation method and application thereof. According to the preparation method disclosed by the invention, in-vitro self-coupling of the rotavirus VP8 protein and the norovirus VP1 protein is realized by utilizing a Spatier-Spytag system, the prepared coupled protein can induce a neutralizing antibody with higher titer aiming at the rotavirus, and the immunogenicity of the norovirus VP1 protein is not influenced; the immunized animal / human body can generate a high-titer specific IgG binding antibody, a serum blocking antibody and a neutralizing antibody aiming at the two viruses. The coupling protein has a wide application prospect in vaccines for resisting infant diarrhea viruses (norovirus and rotavirus).

The invention belongs to the technical field of biological medicine, and particularly relates to a manganese-based delivery system with an adjuvant-like function and application of the manganese-based delivery system in vaccine preparation. The invention firstly provides two novel vaccine vectors, namely PMn and YC-coated PMn. PMn is a novel manganese oxide-polyetherimide complex and is obtained by carrying out redox reaction on potassium permanganate and polyetherimide. PMn can be used for loading antigens, loading adjuvants or can be used as adjuvants per se. PMn is loaded into a hollow yeast microcapsule, and a vaccine delivery system which is more stable and has an adjuvant-like function and a slow-release effect is obtained. The vaccine delivery system can be further loaded with protein antigens and / or other molecular adjuvants. Animal experiments prove that the novel sustained-release vaccine delivery system with the adjuvant-like function can be used for remarkably inducing high-level antigen-specific IgG, IgG1 and IgG2a antibodies in animal bodies.

The present invention belongs to the technical field of biomedicine, and specifically relates to a recombinant influenza virus protein, a vaccine, and a preparation method therefor and the use thereof. To overcome the defects of existing influenza vaccines with respect to safety and high toxic side effects, a recombinant influenza virus protein is provided, which has an amino acid sequence as shown in at least one of SEQ ID No. 1 to SEQ ID No. 6. Recombinant hemagglutinin proteins of H1N1 and H3N2 subtypes, and Victoria and Yamagata lineages are expressed and purified by means of an insect baculovirus expression system, and are mixed with an adjuvant to prepare a highly immunogenic recombinant bivalent, trivalent or quadrivalent recombinant influenza virus protein vaccine. The prepared vaccine can induce high levels of specific IgG antibodies and hemagglutination-inhibiting neutralizing antibodies, the addition of adjuvant WGa01 improves the immunogenicity of the vaccine, and the provided vaccine is suitable for people allergic to eggs and has high safety.

The present application relates to a kind of recombinant bacillus subtilis ASFV polyantigen peptide and the preparation method and application of IL-2 / IFN-alpha display engineering bacteria, belong to animal vaccine technical field.The P30 of the present application, P72, PP220 multi-antigen epitope of ASFV and immune enhancer factor IL-2, IFN-alpha are connected in series, using bacillus subtilis spore surface protein cotG as display carrier, construct recombinant engineering bacteria BSpDG1730-cotGASFV.ELISA and Western blot verification, target protein is efficiently expressed on spore surface and has good stability.Animal experiment shows that, after oral immunization, the engineering bacteria can significantly induce pig to produce specific IgG antibody, improve spleen and thymus index, promote IL-2, IFN-gamma and other cytokine secretion, and also specific fluid and cellular immune response.The preparation process of the present application is simple, spore is resistant to high temperature, easy to store, suitable for large-scale production, and provides a safe, efficient oral vaccine candidate for African swine fever prevention and control.

The invention provides a preparation method and application of a scylla paramamosain allergen Scy p1 hypoallergenic derivative specific I gG antibody, a New Zealand white rabbit is subjected to immune treatment by using a Scy p1 hypoallergenic derivative, and antiserum is purified by using a Protei n A Sepharose affinity chromatography column, so that the purity of the antibody is greatly improved, and the obtained I gG antibody is ensured to have high specificity; the purified antibody is subjected to molecular weight detection through SDS-PAGE (Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis), and an immunoglobulin heavy chain and an immunoglobulin light chain containing 50kDa and 25kDa are defined, so that the quality of the IgG antibody is verified, and a reliable basis is provided for subsequent application; the obtained specific I gG antibody effectively blocks combination of Scy p 1 and I gE in whole blood of a patient in vitro, effectively improves allergic symptoms of mice in vivo, ensures that the prepared I gG antibody is safer and is expected to be used for immunotherapy, and side effects possibly occurring in the treatment process are reduced.