30 results about "Hpv types" patented technology

The invention relates to the technical field of medical detection, in particular to a cervical cancer screening system based on risk HPV (human papillomavirus) expansion typing, and a risk assessment module provides solid technical support for individualized CIN2 + / 3 + risk assessment by using a Bayesian network and a Cox proportional risk model. By dynamically acquiring key data such as HPV types, cytological results, patient ages and infection duration, the Bayesian algorithm is beneficial to constructing individual specific risk models, and real-time risk division is carried out. The Cox regression model predicts accumulated risks in three years, dynamically adjusts a risk assessment threshold value and refreshes the weight of an input variable in real time in combination with a machine learning mechanism, and the composite model structure enables the risk assessment to be more flexible and ensures the scientificity of a management decision.

The present invention relates to the field of bioinformatics, and relates to a method for identifying variant sites that differentiate HPV risk levels, and a use thereof. The identifying method comprises: constructing a guide tree; constructing a phylogenetic tree; marking the phylogenetic tree; determining risk boundary points; performing risk distribution frequency analysis on variant sites; and performing screening to obtain variant sites that meet a preset distribution-frequency condition and variant genotype statuses, that is, characteristic variants for identifying high-risk HPV types. The method of the present invention is used to identify high-risk HPV types, so that large-scale rapid screening and detection based on single nucleotide sites can be achieved without sacrificing accuracy, thereby enabling rapid and precise prevention and control of high-risk HPV types.

The invention discloses a method, a system, equipment and a medium for detecting an HPV (human papilloma virus) DNA (deoxyribonucleic acid) integration event, and relates to the technical field of gene detection. According to the method, HPV types and virus loads (Ct values) pre-screened by qPCR are used as natural identifiers to guide grouping and mixing of samples, and HPV integrated event detection and sample tracing are synchronously realized through single sequencing. Clinical verification shows that compared with qPCR, the comprehensive sensitivity reaches 97.1%, and the cost is reduced by 60%. And a built-in targeted retest mechanism improves the reliability of a detection result. The invention provides a novel, traceable, economical and feasible solution, is used for high-throughput HPV-host genome integration feature analysis, balances cost, expandability and clinical accuracy, and provides a high-throughput and low-cost solution for HPV-related cancer screening.

Methods for treating human papillomavirus (HPV) type 16- or HPV type 18-associated high-grade squamous intraepithelial lesions (HSIL) of the cervix are described

This invention relates to a homogeneous photocatalytic chemiluminescence detection system for detecting HPV vaccine antigen content, its preparation method, and its application. The system utilizes self-made carboxyl-modified donor microspheres and receptor microspheres, coupled with HPV type-specific monoclonal antibodies via EDC / NHS activation, achieving one-step homogeneous detection. By optimizing the microsphere size, a 200 nm microsphere system was found to exhibit higher luminescence signal, a wider detection range, and better sensitivity when detecting HPV16 / 18 VLPs. This method is simple to operate, requires no plate washing, and possesses good specificity, accuracy, and precision. It is suitable for the in vitro relative potency and identification detection of bivalent HPV vaccines, and can replace traditional ELISA methods, reducing detection costs and safety risks. It is also suitable for large-scale applications in vaccine quality control.

The present invention relates to a multivalent HPV immunogenic composition for preventing human papillomavirus (HPV) related diseases or infections and uses thereof. Said multivalent HPV immunogenic composition comprises: HPV virus-like particles assembled from L1 proteins of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and one or more HPV virus-like particles assembled from L1 proteins of other pathogenic HPV types. In one embodiment, said one or more other pathogenic HPV types are selected from HPV Types 35, 39, 51, 56 and 59. In one embodiment, at least one of said HPV virus-like particles is a chimeric HPV virus-like particle, and said chimeric HPV virus-like particle comprises one or more chimeric HPV L1 proteins.

The invention belongs to the field of molecular diagnostic biology, and relates to a primer probe combination, a kit and a detection method for simultaneously and quantitatively detecting 14 high-risk human papilloma viruses, primers comprise an HPV16 primer pair, an HPV18 primer pair, an HPV31 primer pair, an HPV33 primer pair, an HPV35 primer pair, an HPV39 primer pair, an HPV45 primer pair, an HPV51 primer pair, an HPV52 primer pair, an HPV56 primer pair, an HPV58 primer pair, an HPV59 primer pair, an HPV66 primer pair and an HPV68 primer pair; the probes comprise an HPV16 probe, an HPV18 probe, an HPV31 probe, an HPV33 probe, an HPV35 probe, an HPV39 probe, an HPV45 probe, an HPV51 probe, an HPV52 probe, an HPV56 probe, an HPV58 probe, an HPV59 probe, an HPV66 probe and an HPV68 probe. According to the application, 14 high-risk human papilloma virus nucleic acids (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 types) in extracted cervical exfoliated cells can be quantitatively detected, the HPV16 and 18 types can be distinguished, absolute accurate quantitative analysis of the HPV is realized, and the detection sensitivity and accuracy are improved.

This invention belongs to the field of biological detection technology, and particularly relates to a reproductive tract HPV-mRNA-E6 / E7 detection system and method based on nanopore sequencing. The system includes a sample pretreatment module, an RNA extraction and purification module, a reverse transcription module, a nanopore sequencing module, and a bioinformatics analysis module. The method includes the following steps: (1) reproductive tract sample collection and pretreatment; (2) extraction and purification of HPV-mRNA in the sample; (3) reverse transcription of the purified HPV-mRNA into cDNA; (4) nanopore sequencing of the cDNA to obtain raw sequencing data; (5) filtering, comparing, and annotating the sequencing data through the bioinformatics analysis module to achieve HPV type identification and quantitative analysis of E6 / E7 gene expression levels. This invention utilizes the advantages of nanopore sequencing, such as long read length and real-time detection, combined with the specificity of E6 / E7 mRNA as a biomarker of active infection. It can directly detect latent and active HPV infection, improve detection sensitivity, accurately distinguish infection types, and shorten the detection cycle. It enables rapid, accurate, and high-throughput detection of active HPV infection in the genital tract, providing reliable technical support for early screening, disease monitoring, and prognostic assessment of HPV-related diseases such as cervical cancer.

The present invention relates to a chimeric recombinant protein having a therapeutic effect on cervical cancer by fusing genetic modified E6 and E7, which are carcinogenesis-inducing proteins of human papillomavirus high-risk group type 16, with a fusion protein for increasing immunogenicity, the HPV type 16 E6, E7 chimeric recombinant protein fused with the flagellin fusion protein of the present invention showed the lowest tumor cell volume, and the immune response of specific T cells according to the recombinant antigen was significantly confirmed, and when the prophylactic effect was measured, it was confirmed that the volume of tumor cells was low and the antibody titer was increased, therefore human papillomavirus recombinant antigen of the present invention shows tumor treatment and prophylaxis and can be applied as a therapeutic / prophylactic vaccine composition.

The present disclosure provides, inter alia, a vaccine composition comprising a squalene nanoemulsion (SNE) adjuvant and at least one type of virus-like particle (VLP) of human papilloma virus (HPV) selected from the following HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.

The application discloses a quality control product for human papillomavirus molecular detection and a preparation method thereof, and belongs to the technical field of biological products. After synthesizing 25 types of HPV full genomes of high-risk types (HPV16, HPV18, HPV26, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV53, HPV56, HPV58, HPV59, HPV66, HPV68, HPV73, HPV82) and low-risk types (HPV6, HPV11, HPV42, HPV43, HPV44, HPV81, HPV83), the HPV full genomes are connected into a pcDNA3.1(+) skeleton vector system, the HPV full genomes are integrated into the genome of a human ovarian cancer cell line ovcar3 respectively, and 25 strains of human ovarian cancer cell lines stably integrating the HPV full genomes are obtained. The new quality control product or kit of various types of simulated clinical samples such as genomic DNA, cell precipitate and cell suspension can be prepared and is suitable for various detection platforms. The human cell line quality control product stably integrating the full-length genomes of the 25 HPV types can more accurately determine the viral load and control the whole process of HPV detection.

The invention discloses a multivalent expression listeria monocytogenes cervical cancer vaccine and a preparation method thereof. The method comprises the following steps: constructing attenuated listeria monocytogenes of which actA and plcB virulence genes are knocked out; on the basis of the attenuated listeria monocytogenes, constructing to obtain auxotroph listeria monocytogenes LM [delta] dal [delta] dat; the fusion antigen is constructed by alternately arranging amino terminal and carboxyl terminal structural domains of multiple types of E6 and E7 proteins of HPV (human papillomavirus); inserting the fusion antigen into a non-resistance plasmid pCW631 which carries a dal gene and replaces an Amp gene with an asd gene through PCR (Polymerase Chain Reaction) amplification, gel recovery and seamless cloning technologies to obtain a non-resistance plasmid pCW636; the non-resistance plasmid pCW636 is electrically transferred into the auxotroph listeria monocytogenes LM [delta] dal [delta] dat, and the listeria monocytogenes cervical cancer vaccine is obtained after PCR (polymerase chain reaction) screening, product verification and sequencing. The cervical cancer vaccine for multivalent expression of the E6E7 protein is constructed on the basis of the attenuated listeria monocytogenes, and multiple protection on cervical cancer can be achieved.

The present method allows for detection of at least nine HPV types in a real-time manner in one reaction vessel by analyzing signals measured at three temperatures using at least three different types of fluorescent labels. In particular, the method of the present invention can detect at least nine target nucleic acids in a real-time manner without performing a melting analysis.

Methods of treating human papilloma virus type 16 (HPV) or HPV type 18 associated high-level squamous intraepithelial lesions (HSIL) of the cervix are described.

The application discloses application of primers and a combination of probes in preparation of a kit for detecting HPV, wherein the nucleotide sequence of the primers is shown as SEQ ID NO: 15-42; and the nucleotide sequence of the probes is shown as SEQ ID NO: 1-14. The application overcomes problems of long detection time, high false negative rate and high operation technical threshold in traditional cervical cancer screening methods, provides primers and probes for detecting 14 high-risk HPV types, and provides a corresponding detection kit, which not only simplifies the operation process, reduces the cost and technical complexity, but also greatly shortens the time of cervical cancer screening, has high specificity, is suitable for large-scale preliminary screening of cervical cancer in clinical application, and has popularization and application value.

The present disclosure provides, among other things, a pharmaceutical composition that includes a lipid nanoparticle adjuvant and an anti-human papillomavirus (HPV) comprising HPV virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.

This invention relates to the field of biological detection, and more particularly to primer combinations, reagent kits, and their applications. The invention provides primer combinations including: primer set I, primer set II, primer set III, primer set IV, primer set V, primer set VI, primer set VII, primer set VIII, primer set IX, primer set X, primer set XI, primer set XII, primer set XIII, primer set XIV, primer set XV, primer set XVI, primer set XVII, primer set XVIII, primer set XIX, primer set XX, primer set XXI, primer set XXII, and primer set XXIII. This invention also provides a reagent kit for rapid HPV detection. This kit can rapidly detect the above 23 HPV types within 20 minutes. The detection limit of the kit is up to 10. 3 The accuracy and specificity are good, with a per-copy / mL ratio.

The invention relates to the technical field of biological detection, in particular to a primer combination, a probe combination and a detection product of a high-risk human papilloma virus E6 / E7mRNA genetic typing detection reagent and application thereof. A specific probe adopting a cross-exon strategy is adopted, so that an amplification product crosses at least one intron region, transient and persistent HPV infection can be distinguished, a primer and probe combination for detecting 14 high-risk human papilloma virus E6 / E7 region mRNA is provided, and through a multiple PCR (Polymerase Chain Reaction) and melting curve combined technology, the detection sensitivity of the HPV E6 / E7 region mRNA is improved, and the detection sensitivity of the HPV E6 / E7 region mRNA is improved. 14 high-risk HPV type E6 / E7mRNA can be simultaneously detected and specifically typed through single-tube reaction, the coverage range is far beyond that of a traditional fluorescent PCR method (generally only 2-4 types are detected), melting curve characteristic difference (for example, Tm value difference is larger than or equal to 0.5 DEG C) is combined with autonomous analysis software, accurate distinguishing of homologous types (for example, HPV 52 / 35) is achieved, cross reaction is avoided, and the typing accuracy is gt; 99%.

The invention belongs to the technical field of HPV (human papillomavirus) detection, and particularly relates to a primer probe group and a kit for specific recognition and rapid detection of fourteen high-risk HPVs based on an RPA (recombinase polymerase amplification) isothermal amplification method, and application of the primer probe group and the kit. The primer probe group comprises a primer group and a probe group, wherein the primer group comprises a peripheral upstream primer with a nucleotide sequence as shown in SEQ ID NO: 1, a peripheral downstream primer with a nucleotide sequence as shown in SEQ ID NO: 2 and a peripheral downstream primer with a nucleotide sequence as shown in SEQ ID NO: 3; the nucleotide sequence of the peripheral downstream primer is as shown in SEQ ID NO: 2. The primer probe set and the kit have high sensitivity and high specificity, the detection sensitivity of the primer probe set and the kit to HPV high-risk viruses can reach 100 copies / mL, and the performance is superior to that of existing detection products in the market; the design of the specific probe can accurately detect fourteen high-risk HPV types, and does not generate cross reaction with low-risk HPV types or other viruses. The whole detection process is carried out at room temperature, laboratory operation is not needed, the detection time is about 30 minutes, and the detection can be completed in one detection rod.

The invention provides a fusion gene and an HPV nucleic acid vaccine. A fusion gene is obtained through research and optimization, and the fusion gene is obtained by sequentially connecting an L1 gene of an HPV 16 type, an E5 gene, an E6 gene and an E7 gene of the HPV 16 type and an E5 gene, an E6 gene and an E7 gene of an HPV 52 type. The inventor finds that an HPV vaccine prepared by taking the fusion gene as an antigen component can effectively promote cellular immune response and formation of long-term protective memory, promote hair growth center response and formation of humoral immune memory, remarkably improve the proportion of NKT cells, successfully activate systemic anti-tumor cell immune response of mice, and improve the anti-tumor effect of the mice. The anti-tumor immune effect is greatly improved. The traditional Chinese medicine composition has the dual effects of prevention and treatment, has the prevention capability, can effectively inhibit tumor growth and has the tumor treatment capability. The HPV vaccine also has the advantages of high safety, good stability and the like, and has a wide application prospect.

The present method allows for detection of at least nine HPV types in a real-time manner in one reaction vessel by analyzing signals measured at three temperatures using at least three different types of fluorescent labels. In particular, the method of the present invention can detect at least nine target nucleic acids in a real-time manner without performing a melting analysis.

The invention provides a multiple RPA-CRISPR detection system aiming at human papilloma virus typing, the multiple RPA-CRISPR detection system comprises an RPA isothermal amplification module, a CRISPR multiple detection module and a signal output module, the RPA isothermal amplification module comprises RPA amplification primers targeting eight HPV subtypes 16, 18, 11, 31, 33, 45, 52 and 58 and two freeze-drying balls, and one-tube multiple amplification is carried out on a sample; the CRISPR multiple detection module comprises a multiple microcavity device, a detection system pre-embedded in the multiple microcavity device and a constant-temperature heating pad; and the signal output module is a lateral flow chromatography test strip. The invention also provides an application of the multiple RPA-CRISPR detection system and a detection method of the multiple RPA-CRISPR detection system. According to the invention, a plurality of reaction steps and reagents are integrated by virtue of the micro-fluidic chip, so that POC detection of the eight high-risk HPVs is realized.

The invention discloses application of dextran sulfate sodium in preparation of a medicine for treating and preventing human papilloma virus infection. According to the application, the action effect of the dextran sulfate on inhibiting human papilloma virus type 6, type 16, type 18 and type 58 pseudoviruses from entering 293FT cells is evaluated at the cellular level, and the result shows that the dextran sulfate can effectively inhibit the human papilloma virus type 6, type 16, type 18 and type 58 from infecting the 293FT cells. Results of inhibition of human papilloma virus 16 pseudovirus infection by sodium dextran sulfate according to animal level evaluation show that sodium dextran sulfate can effectively inhibit infection of human papilloma virus 16 pseudovirus on mouse genitals. Sodium dextran sulfate has the advantages of blocking HPV virus from invading cells, preventing virus from expanding infection, being safe, stable, low in cost and the like, and the medicine has the prospect of being developed into a preparation for treating or preventing human papilloma virus infection related diseases.

The invention provides a high-risk subtype HPV (human papillomavirus) tumor vaccine and application thereof, the high-risk subtype HPV tumor vaccine comprises nano lipid particles and RNA (Ribonucleic Acid) for expressing HPV antigens, the RNA for expressing the HPV antigens comprises RNA for coding HPV peptide epitopes, the HPV peptide epitopes comprise protein E6 and E7 recombinant protein, and the nano lipid particles wrap the RNA. The vaccine has the advantages that the independently researched and developed nano lipid particles can wrap a plurality of RNAs at the same time, and E6 and E7 antigens of various high-risk HPVs are effectively expressed. In RNA molecular design, fusion expression is carried out in a form of series connection of E6 and E7, and efficient translation of a nucleic acid sequence is realized through codon optimization. The vaccine can effectively activate in-vivo tumor specific immune response and ensure safety at the same time, and treatment of various high-risk HPV related cancers is taken into consideration in clinical application.

The application provides a primer composition for detecting different types of human papilloma virus and application thereof, and relates to the technical field of nucleic acid determination or detection methods.The primer composition provided by the application comprises a first primer and a second primer for detecting HPV type 16, a third primer and a fourth primer for detecting HPV type 18, and a fifth primer and a sixth primer for detecting HPV high-risk types.The primer composition provided by the application can realize multiplex detection of human papilloma virus, has the characteristics of good specificity, high sensitivity and good repeatability, and can avoid the false positive problem existing in conventional primers.Based on the primer composition, the application further combines an immunochromatography test strip detection technology to realize rapid and efficient detection of human papilloma virus, and the operation is simple and relatively portable, and the application can be used for home self-detection.

The present invention discloses a multivalently expressed Listeria monocytogenes cervical cancer vaccine and a preparation method thereof, wherein the method comprises replacing the Listeria monocytogenes LIΔ with hemolysin. in :: hly Based on this, the auxotrophic Listeria ovis LIΔ was constructed. in :: hly Δ from the Δ given The fusion antigen was constructed by alternately arranging the amino-terminal and carboxyl-terminal domains of the E6 and E7 proteins of the four HPV types 6 / 11 / 16 / 18 and retaining the overlapping region of 16 amino acids at the junction site; the fusion antigen was inserted into the carrier from the Gene combination asd Gene replacement Amp Gene non-resistance plasmid pCW631, obtain non-resistance plasmid pCW636; the non-resistance plasmid pCW636 is electroporated into the auxotrophic Listeria ovis LIΔ in :: hly Δ from the Δ given The cervical cancer vaccine of the present invention can multivalently express E6E7 proteins to achieve multiple protection against cervical cancer.

The invention belongs to the technical field of biological medicine, and particularly discloses a human papilloma virus (HPV) 16 type E7 / E6E7 mRNA therapeutic vaccine and application thereof. HPV 16 type E7 mutant protein or E6E7 fusion protein and specific 5 'UTR, signal peptide, 3' UTR and poly (A) tail are inserted into modified pVAX-1 plasmid through a seamless cloning method to form an mRNA expression vector for expressing HPV E7 protein and / or E6E7 fusion protein, mRNA is synthesized after in-vitro transcription, and the mRNA vaccine is formed after liposome (LNP) encapsulation. The vaccine is administered through intramuscular injection or intratumor injection; or vaccine and chemical medicine are combined for administration. The vaccine provided by the invention can inhibit the growth of tumors, prolong the survival time of tumor-bearing mice, enhance cellular immune response and improve the tumor microenvironment, and shows huge potential for treating HPV-related cancers.

The invention relates to the technical field of papilloma virus antigen composite peptides, in particular to a preparation method and application of a papilloma virus antigen composite peptide. The composite peptide is selectively combined and activates specific immune cells, so that the immunity of a host to HPV infection is enhanced. The preparation method comprises the following steps: screening antigenic determinants with high immunogenicity from various HPV types, and combining the antigenic determinants with helper T cell epitopes to form a polypeptide chain. The polypeptide chain is produced through chemical synthesis or a DNA recombination technology, and then the high-purity composite peptide is obtained through a purification step. The composite peptide can be used as a vaccine component or a therapeutic agent, is applied to prevention of HPV related diseases such as cervical cancer, anal cancer and other skin and mucous membrane lesions, and can also be used as a key component in a diagnostic reagent. In addition, the composite peptide is also suitable for developing personalized cancer immunotherapy, and provides a more effective treatment scheme for patients affected by HPV.

The invention discloses a traditional Chinese medicine preparation for improving HPV (human papillomavirus) infection symptoms and a preparation method of the traditional Chinese medicine preparation. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 40-60 parts of raw coix seeds, 25-35 parts of oldenlandia diffusa, 15-25 parts of anhydridized bovine beta-lactoglobulin, 8-12 parts of curcumin, 10-20 parts of lentinan, 20-30 parts of astragalus membranaceus, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 20-28 parts of rhizoma smilacis glabrae and 4-8 parts of liquorice. According to the invention, through the charge adsorption effect of the anhydridized bovine beta-lactoglobulin and the HPV capsid protein, the broad-spectrum physical blocking of more than 200 HPV types is realized; the curcumin and the lentinan are combined for use, HPV E6 / E7 gene expression is synchronously inhibited, CD8 + T cell immune clearance is activated, the recurrence rate of viruses in the incubation period is reduced, the astragalus membranaceus and the lentinan cooperate to balance Th1 / Th2 immune response, and immune migration is avoided; the raw coix seeds and the rhizoma smilacis glabrae regulate the pH value and flora balance of a genital tract microenvironment and promote skin damage repair, and all the components have a synergistic effect through a'blocking-inhibiting-clearing-repairing 'quadruple mechanism, so that the clinical negative conversion rate can be increased.

Embodiments of the present invention provide for novel compositions and methods for making and using a thermally stable broad spectrum human papilloma virus (HPV) vaccine or immunogenic formulation. Certain embodiments concern lyophilizing HPV formulations in the presence or absence of adjuvants. Other embodiments concern lyophilizing HPV capsomere vaccines and other immunogenic agents to increase stability or reduce degradation of HPV peptides to prolong storage, delivery and use. In yet other embodiments, a single immunogenic formulation can include a thermally stable composition of a broad-spectrum HPV immunogenic composition against multiple HPV types. In some embodiments, a stabilizing formulation can include RG1 HPV16VLP antigens in a hypertonic mixture of a disaccharide and a volatile buffer.