77 results about "Attenuated strain" patented technology

The invention relates to the technical field of biological medicines, in particular to a tuberculosis vaccine antigen and a vaccine. In particular to application of a mycobacterium tuberculosis Rv1787 gene in preparation of a vaccine for preventing and / or treating tuberculosis, in the application, the sequence of the Rv1787 gene or an encoding product thereof is defined, and the Rv1787 gene and the encoding product thereof serve as antigens, have mycobacterium tuberculosis specificity, and can be used for preparing a vaccine for preventing and / or treating tuberculosis. According to the mycobacterium tuberculosis vaccine, identification and response of an organism immune system to mycobacterium tuberculosis can be accurately stimulated, non-specific immune response to other normal tissues is avoided, a brand new and specific molecular target spot is provided for preventing and treating tuberculosis, and the limitation that a traditional vaccine depends on a single antigen or an attenuated strain is broken through. A specific expression product of the gene can stimulate directional recognition and attack of an organism immune system on mycobacterium tuberculosis, the pertinence and effectiveness of vaccines are remarkably improved, and a new path is provided for solving the problem of tuberculosis prevention and treatment.

The invention provides a Garlu virus attenuated strain and application thereof, and relates to the field of virology and biological medicine. According to the invention, the screened Garlu virus attenuated strain is a natural attenuated strain derived from a tick sample, can grow in Vero cells, has the titer of more than or equal to 107 TCID50 / mL, does not have clinical pathogenicity to an immunodeficient host, and is safe; after the attenuated strain is used as an immunogen for pre-intervention, infection of a lethal virus strain can be avoided, the survival rate is increased to 100%, adverse effects on growth and life of experimental animals are avoided, particularly, a host can be stimulated to generate humoral immunity and cellular immunity at the same time, and the survival rate of the experimental animals is improved. And moreover, broad-spectrum cross-protection efficacy can be generated on Bandavirus lethal virus strains, and a foundation is laid for improvement of research on Bandavirus live vaccines such as the Colu virus and the like.

The invention belongs to the field of strains, and particularly relates to a botryosphaeria dothidea attenuated strain ZMXX551-1 containing a penicillium-producing virus BdCV2 and application of the botryosphaeria dothidea attenuated strain. The attenuated strain ZMXX551-1 is preserved in the China General Microbiological Culture Collection Center on June 25, 2025, the preservation number is CGMCC NO.42040, the genome of the penicillium virus BdCV2 is composed of four dsRNAs, the penicillium virus BdCV2 has a remarkable effect in the aspect of weakening the pathogenicity of botryosphaeria dothidea, the attenuated strain ZMXX551-1 is used for treating peach seedlings, the length of scabs is inhibited by 8.63%, and the length of the scabs is inhibited by 8.63%. After 3 months, the scab of the treatment group begins to heal, and the scab of the control group is continuously increased, which indicates that the peach seedling inoculated with the strain ZMXX551-1 grows well; therefore, the strain ZMXX551-1 can inhibit expansion of peach gummosis scabs and improve plant growth, and has biological control potential.

The invention relates to the technical field of biological medicines, and discloses a construction method and expression application of an Hcp gene deleted strain of a rahnella aqua KCL-5 strain for fish. The Hcp 0186 gene deletion strain is constructed by using a homologous recombination method, the comparison between the deletion strain and a wild strain is carried out, and the result shows that the deletion of the Hcp 0186 gene has an influence on the growth speed, the pathogenicity of the Hcp 0186 gene to the zebra fish is obviously reduced, the survival rate of the infected zebra fish is increased from 0% to 52%, and the Hcp 0186 gene deletion strain can be used as a fish attenuated live vaccine. A recombinant prokaryotic expression vector pET32a-Hcp and expression and purification of fusion protein of the recombinant prokaryotic expression vector pET32a-Hcp are further constructed, and Hcp 0186 rabbit polyclonal antibody serum is prepared as a primary antibody and can be applied to localization expression analysis of fish tissues infected by the bacterium and detection of WB and IHC. Results prove that the Hcp 0186 gene deletion of the strain provides an attenuated strain vaccine and clinical diagnosis and detection application of infected fish of the attenuated strain vaccine, and a scientific basis can be provided for revealing a molecular pathogenic mechanism of the strain and development and application of a mutant strain of the strain.

The invention discloses a bovine virus diarrhea live vaccine based on suspension culture and a preparation method thereof, and relates to the field of animal vaccines. The bovine viral diarrhea virus vaccine is a freeze-dried vaccine, and each vaccine contains a bovine viral diarrhea virus BVDV attenuated strain antigen and a freeze-drying protective agent; wherein the virus content of the antigen of the BVDV attenuated strain is 105-107 CCID50 / piece, and the BVDV attenuated strain is a cytopathic effect type attenuated strain suitable for suspension culture; the freeze-drying protective agent comprises trehalose, cane sugar, gelatin hydrolysate, sodium glutamate and polyvinylpyrrolidone. The suspension culture technology is adopted, large-scale, efficient and stable production of BVDV antigens is achieved, an optimized freeze-drying formula is combined, the obtained vaccine is high in virus titer, good in immunogenicity, high in stability, good in safety, advanced in production process, controllable in cost and suitable for industrial large-scale production.

The invention belongs to the technical field of biological medicine, and discloses a toxoplasma gondii in-vitro merozoite induction model and a construction method thereof. The invention discloses application of a glutamine antagonist to induction of differentiation of toxoplasma gondii tachyzoite to merozoite or preparation of a product for induction of differentiation of toxoplasma gondii tachyzoite to merozoite, and finds that the glutamine antagonist JHU083 can induce differentiation of toxoplasma gondii virulent strain RH and attenuated strain ME49 tachyzoite into merozoite under in-vitro conditions for the first time. A reliable in-vitro model is provided for researching the key initial stage of sexual reproduction of the toxoplasma gondii, and an irreplaceable research foundation is laid for the key link of targeted blocking of parasite transmission.

The invention relates to the technical field of biology, and discloses a Zika virus non-structural protein 1 functional site and application thereof in design of a Zika virus attenuated strain. According to the invention, a new Zika virus virulence site is innovatively found, and a basis is provided for research of Zika virus and research and development work of related drugs. The invention also provides an attenuated mutant strain constructed on the basis of the virulence site, and the attenuated mutant strain has obvious attenuated characteristics and higher genetic stability, and can be used as an alternative strain of a Zika virus attenuated live vaccine.

The invention discloses a riemerella anatipestifer double-gene deletion attenuated vaccine candidate strain, a construction method and application, the riemerella anatipestifer double-gene deletion attenuated vaccine candidate strain is a riemerella anatipestifer CH-1 strain B739RS01935-B739RS07625 double-gene deletion attenuated vaccine candidate strain, the preservation number is CCTCC NO: M20251080, the preservation date is May 22, 2025, and the preservation number is CCTCC NO: M20251080. The strain is preserved in China Center for Type Culture Collection, and the address of the preservation unit is Wuhan University, Wuhan, China. After ducklings are immunized by the low virulent strain, the low virulent strain has no obvious influence on weight proliferation of the ducklings and has good safety. And after the ducklings are immunized, the challenge protection rate on RACH-1 wild virulent strains reaches 83.3%, and the immune protection effect is good.

The invention relates to the field of veterinary biological products, in particular to a porcine epidemic diarrhea virus attenuated strain and a vaccine and application thereof. The porcine epidemic diarrhea virus attenuated strain provided by the invention is obtained through in-vitro separation culture and continuous five rounds of plaque purification and screening technology, and has stable culture characteristics. Meanwhile, the virulence of the strain on newborn piglets and weaned piglets is remarkably reduced, and the virulence does not have the phenomenon of reversion after continuous passage for five times in a pig body. The strain has good immunogenicity, and mucosal immunity and systemic immune response of an organism can be activated at the same time by adopting an oral immunization mode. A neutralizing antibody of 1: 8-1: 16 can be detected in oral fluid and serum after the piglets are immunized for 14 days, and a large amount of sIgA is generated in milk after the pregnant sows are immunized, so that the piglets obtain effective passive immune protection.

The invention discloses a streptococcus agalactiae attenuated strain, a vaccine and application of the streptococcus agalactiae attenuated strain, and belongs to the technical field of veterinary biological products. The streptococcus agalactiae attenuated strain is obtained by knocking out a marR gene of a streptococcus agalactiae virulent strain HN016; wherein the nucleotide sequence of the marR gene is as shown in SEQ ID NO: 1. After the marR gene of the streptococcus agalactiae virulent strain HN016 is knocked out, the streptococcus agalactiae attenuated strain of which the virulence is remarkably reduced is obtained, and after the streptococcus agalactiae attenuated strain is prepared into the vaccine, the survival rate of aquatic animals infected with streptococcus agalactiae can be remarkably improved, so that the survival rate of the aquatic animals infected with streptococcus agalactiae is improved. The streptococcus agalactiae attenuated strain has a good application prospect in preparation of drugs for preventing and / or treating streptococcus agalactiae infection of aquatic animals.

The present invention discloses a canine coronavirus attenuated strain CCoVAS22 and its application, and relates to the field of biomedicine technology. The canine coronavirus attenuated strain CCoVAS22 was deposited in the China Center for Type Culture Collection on July 12, 2024, and the deposit address is Wuhan University, Wuhan, China, and the deposit number is CCTCC NO: V202413. The present invention utilizes the technical means of cross-passaging in MDCK and CRFK cell lines to obtain an independently isolated CCoVAS22 strain, which has the advantages of high toxicity and stable passage on cells. After inactivation by β-propiolactone, it has the characteristics of high safety and good immunogenicity. It can be used as a candidate strain for CCoV inactivated vaccine, which can alleviate the problem of the small number of canine coronavirus isolates in China to a certain extent, and provide technical support for the prevention of diseases caused by canine coronavirus.

The invention discloses an application of docetaxel in preparation of drugs for resisting toxoplasmosis, and belongs to the technical field of medicines. Through a series of experimental studies, it is found that docetaxel can significantly delay the onset time of mice infected with toxoplasma gondii virulent strains and effectively reduce the death rate of mice infected with toxoplasma gondii attenuated strains. Docetaxel shows a relatively strong inhibition effect in the aspect of treating related diseases caused by a virulent strain or a low virulent strain of toxoplasma gondii, and can effectively slow down the infection process and prolong the life cycle of a host. In combination with in-vitro cell experiment and in-vivo animal experiment results, the taxane drug has a good treatment prospect, can be used as a development basis of a novel toxoplasmosis-resistant drug, and promotes the realization of a novel treatment scheme.

The invention relates to a recombinant rabies virus. The recombinant rabies virus is obtained by inserting an antigen gene of feline calicivirus and an antigen gene of feline herpes virus into a genome of a rabies virus attenuated strain. The triple inactivated vaccine for preventing and treating the feline calicivirus disease, the feline herpes virus disease and / or the rabies is prepared based on the recombinant rabies virus, and after the triple inactivated vaccine is used for immunizing cats, neutralizing antibodies aiming at the feline calicivirus disease, the feline herpes virus disease and the rabies virus can be effectively induced and generated; the simultaneous immunization on the three viruses is realized.

The application provides a construction method and application of a Toxoplasma gondii attenuated strain PruDelta pp2a-c and belongs to the technical field of biological medicine. The TgPP2A-C gene is knocked out to obtain a TgPP2A-C gene deletion Toxoplasma gondii attenuated strain. After the gene is deleted, a large number of starch granules are aggregated between the bodies of the Toxoplasma gondii, and the Toxoplasma gondii loses the ability to form cysts. The in-vitro proliferation speed and pathogenicity of the TgPP2A-C gene deletion Toxoplasma gondii attenuated strain are significantly reduced compared with those of a wild strain. After being infected with the TgPP2A-C gene deletion strain, a mouse does not get ill or die, and no cysts are detected in the brain tissue of the mouse, so the TgPP2A-C gene deletion strain has high safety to a host. After a mouse is immunized with the TgPP2A-C gene deletion Toxoplasma gondii attenuated strain, the antibody level of the mouse is significantly improved, and the mouse can provide significant immunoprotection efficacy against high-dose Toxoplasma gondii RH tachyzoite and Pru cyst re-infection, and can prevent re-infection of Toxoplasma gondii.

The invention discloses Guanzhong donkey plasma canine parvovirus immune globulin CPV-IgG, a freeze-dried product, a preparation process and application, and relates to the technical field of bioactive components and separation and purification. The method comprises the following steps: selecting a canine parvovirus CPV-XN1 low virulent strain as an immunogen to immunize an animal; the method comprises the following steps: collecting plasma of an immune animal, and purifying to obtain canine parvovirus immune globulin CPV-IgG. The SN titer of the obtained immune globulin CPV-IgG is not lower than 1: 256. The invention further provides a freeze-drying agent matched with the immune globulin CPV-IgG. The freeze-drying agent is prepared from, by mass, 6 parts of gelatin with the mass concentration being 2.6%, 2 parts of lactose with the mass concentration being 2.8%, 1 part of glycine with the mass concentration being 2.6% and 1 part of sodium chloride with the mass concentration being 2.34%. The lyophilized product obtained after mixing with immune globulin according to the volume ratio of 1: 1 has the potential of preparing the clinical treatment medicine for canine parvovirus infection.

The invention discloses a coronavirus attenuated strain, a vaccine as well as a preparation method and application of the coronavirus attenuated strain. Compared with a natural strain, the coronavirus attenuated strain disclosed by the invention at least comprises deletion of a No.5 stem loop (Stem-loop 5, SL5) from the 131 site to the 350 site of a 5 '-non-coding region (5' UTR) or mutation of any nucleotide maintaining a stem loop structure in a second stem loop from the 175 site to the 299 site of the SL5; compared with a natural strain, the virulence of the SL5-deleted mutant virus strain is obviously reduced; the SL5-deficient mutant virus strain has better genetic stability, and the carried virus genome has no risk of being integrated into the host cell genome. Therefore, the coronavirus attenuated strain disclosed by the invention can be used as an attenuated live vaccine for preventing coronavirus infection, and has a good application prospect.

The invention relates to a primer and a locked nucleic acid probe set for real-time fluorescent quantitative PCR detection of two goose parvovirus virulent and attenuated strains, the goose parvovirus virulent and attenuated strains comprise MDGPV virulent and attenuated viruses and SBDSV virulent and attenuated viruses, and the sequences of the primer and the locked nucleic acid probe set are respectively shown as SEQ ID NO.1-8. The LNA-TaqMan real-time fluorescent quantitative PCR detection method established by utilizing the primers and the LNA-TaqMan probe group can be used for simultaneously detecting strong and weak goose parvovirus strains (strong and weak muscovy duck gosling plague virus and / or strong and weak duck short beak and dwarf syndrome virus), identifying, diagnosing and accurately quantifying, and is high in sensitivity, strong in specificity and good in repeatability.

The invention belongs to the field of vaccine microorganisms, and provides a swine pasteurella multocida attenuated strain PmA4-750, which is preserved in the China Center for Type Culture Collection (CCTCC), and the preservation number is CCTCC NO: M 20251644. The invention further provides a preparation method of the swine pasteurella multocida attenuated strain PmA4-750. After alternate high-temperature continuous passage, three generations of whole-gene sequencing and pathogenicity contrast tests find that a vaccine candidate strain (PmA4-750 strain) has a section of specific insertion fragment with the length of about 43kb, and 14 genetic variation sites, including 10 InDel (insertion / deletion) and 4 SNP (single nucleotide polymorphism), exist in the vaccine candidate strain. The inserted genes may generate adaptive evolution of strains in the passage process of the strains, so that the pathogenic characteristics of the strains are changed, and the toxicity is promoted to be remarkably reduced. In addition, a piglet immune challenge protection test result shows that the PmA4-750 strain has an immune effect on swine pasteurellosis caused by type A, type D or type B pasteurella multocida. In addition, the invention also discloses a swine pasteurellosis live vaccine and a preparation method thereof.

The invention discloses a metabonomics-based method for distinguishing a vibrio alginolyticus wild type virulent strain and a crp gene deletion type weak strain. According to the method, a vibrio alginolyticus virulent strain and a crp gene deletion type attenuated strain are distinguished according to the ratio of the content of arabinose to the content of myristic acid in vibrio alginolyticus measured by metabonomics, and the vibrio alginolyticus crp gene deletion type attenuated strain with the ratio of arabinose to myristic acid in a sample to be detected being 5.9 or above is the vibrio alginolyticus crp gene deletion type attenuated strain. The vibrio alginolyticus strain with the ratio of arabinose to myristic acid being less than 1.5 is a vibrio alginolyticus wild type The method is simple to operate and reliable in detection result, and can provide reference for vibrio alginolyticus crp metabolic characteristic analysis and related vibrio alginolyticus crp metabonomics research.

The invention discloses a virulence-attenuated bovine nodular skin disease virus LSDV-75 and application thereof, and belongs to the technical field of attenuated strains. The invention aims to provide a bovine nodular skin disease virus vaccine strain which is sufficient in attenuation and good in immune effect. The invention provides a virulence-attenuated bovine nodular skin disease virus strain, which is named as sheep pox virus LSDV-75, has the preservation number of CCTCC NO: V2024114, and is preserved in the China Center for Type Culture Collection on December 2, 2024. The vaccine strain provided by the invention can be used as a vaccine candidate strain for safely and effectively preventing and controlling bovine nodular dermatosis.

The invention discloses construction and application of a Candida albicans attenuated strain with deletion of a COX17 gene, and belongs to the technical field of genetic engineering, the Candida albicans attenuated strain is a Candida albicans COX17 deletion strain without expression of the COX17 gene, the invention further provides a Candida albicans treatment drug, the drug takes the COX17 gene as a target spot, and the COX17 gene is used as a target spot to prepare the Candida albicans COX17 deletion strain. The invention further discloses application of the Candida albicans attenuated strain with the deletion of the COX17 gene in preparation or screening of Candida albicans treatment drugs, the invention further discloses application of the Candida albicans attenuated strain with the deletion of the COX17 gene in toxicity regulation, and a new medicament and a new direction are provided for drugs for treating Candida albicans infection.

The invention discloses a human-sheep rotavirus gene reassortment attenuated strain LG1 and application of the human-sheep rotavirus gene reassortment attenuated strain LG1. The human-sheep rotavirus gene reassortment attenuated strain LG1 comprises: i) a coding gene of a structural protein VP7 of a human G1 type rotavirus HN15D2 strain; and ii) coding genes of structural proteins VP1, VP2, VP3, VP4 and VP6 and non-structural proteins NSP1, NSP2, NSP3, NSP4 and NSP5 of the sheep rotavirus strain LLR. The human-sheep rotavirus gene reassortment strain which takes a sheep rotavirus strain as a skeleton, contains a human G1-VP7 gene and can be stably passaged on a Vero cell is successfully constructed for the first time, and the reassortment strain not only has the safety of an animal strain, but also has the immunogenicity of a human G1 type RV, can effectively prevent infection of a human G1 type wild strain, and has a good application prospect. The method has important significance for developing multivalent RV vaccines containing G1 genotypes and developing RV vaccines which are higher in prevention pertinence and provide a better protection effect on Chinese infantile diarrhea.

The invention provides attenuated mutant bacillus anthracis as well as a preparation method and application thereof, and the preparation method comprises the following steps: S1, inserting a first design sequence into a plasmid pMAD to construct a PA gene point mutation plasmid; step S2, constructing a PA mutant Sterne strain by using the Sterne strain and the PA gene point mutation plasmid; and step S3, constructing a pK-Cre vector, and constructing a Stern mPA strain without Erm resistance by using the pK-Cre vector and the PA mutant Stern strain. The prepared vaccine strain is an anthrax vaccine Sterne mPA obtained by genetic engineering modification based on the Sterne vaccine, and an attenuated strain obtained by performing multiple point mutations on a protective antigen (PA), and has the advantages that the capability of generating anthrax toxin and the lethal toxicity effect are lost. And the safety and the effectiveness are obviously improved.

The application discloses an attenuated strain of pathogenic Aeromonas hydrophila and application of the attenuated strain in preparation of a vaccine, relates to the technical field of vaccines, and discloses the following technical scheme. exeA and pspA The attenuated strain is obtained by introducing a suicide plasmid pRE112 plasmid carrying a gene deletion fragment into wild-type Aeromonas hydrophila, the attenuated strain has significantly reduced virulence compared with the wild-type strain, has good immunoprotective capacity, and has a relative immunoprotective rate of 72.73%, which is significantly higher than the relative immunoprotective rate 53.03% of the immersion inactivated vaccine, and can effectively protect fish from the infection of the wild-type strain of Aeromonas hydrophila.

The invention provides a bovine nodular dermatosis virus passage attenuating method and application thereof.The method comprises the steps that a bovine nodular dermatosis virus LSDV NM2020 strain serves as a parent strain, 25 generations of continuous passage is conducted through 9-day-old SPF chick embryo chorioallantoic membrane, 30 generations of continuous passage is conducted in Vero E6 cells in a gradual cooling mode, and finally the attenuated strain is obtained through plaque cloning and purification; the strain is named as an LSDV-Z strain. The low virulent strain shows good safety in cattle while keeping the growth titer close to that of a parent strain, does not cause clinical symptoms and does not have an external detoxification phenomenon. A virus attack protection test proves that the LSDV-Z strain can provide 100% immune protection for virulent virus attack. The method disclosed by the invention has the advantages of short attenuation period, high efficiency, no need of transgenic operation and the like, and the obtained LSDV-Z strain can be used as a safe and effective candidate vaccine strain and is used for preventing and controlling bovine nodular dermatosis.

This invention provides an attenuated vaccine against Coxsackievirus A6 (CVA6), its preparation method, and its application. By comparing a highly pathogenic clinical isolate (CVA6-HeB) with an attenuated strain (CVA6-TW141), the genetic basis of CVA6 virulence was systematically studied. This invention located the core virulence determinant to the P1 capsid region and identified a key lethal amino acid residue (VP3-238) that significantly weakens viral replication in target tissues. Based on this discovery, this invention designed and validated a candidate attenuated live vaccine with significantly reduced lethality.

Provided are an F-genotype mumps virus attenuated strain, a construction method therefor and an application thereof. The attenuated strain is a mumps virus with the accession number of CCTCC NO: V201950. Further provided are a vaccine composition containing the F-genotype mumps virus attenuated strain as an active ingredient and a preparation method thereof.

The invention discloses a rotavirus reassortment attenuated strain LG12 and application of the rotavirus reassortment attenuated strain LG12. The rotavirus reassortment attenuated strain LG12 comprises: i) a coding gene of a structural protein VP7 of a human G12 type rotavirus strain G12P [6]; and ii) coding genes of structural proteins VP1, VP2, VP3, VP4 and VP6 and non-structural proteins NSP1, NSP2, NSP3, NSP4 and NSP5 of the sheep rotavirus strain LLR. The reassortment strain provided by the invention has the safety of animal strains and the immunogenicity of human G12 type RV, can effectively prevent infection of human G12 type wild strains, and can have different degrees of cross protection on infection of other various G type RV wild strains; the method has great significance for developing RV vaccines which cover more G and P genotypes of Chinese epidemic RVA, have stronger prevention pertinence and provide a better protection effect on Chinese infantile diarrhea.

The invention discloses a construction method and application of a toxoplasma gondii attenuated strain RH ncl1, and belongs to the technical field of biological medicines. According to the invention, the TgNCL1 gene is knocked out to obtain the toxoplasma gondii attenuated strain with deletion of the TgNCL1 gene, the in-vitro proliferation speed of the toxoplasma gondii with deletion of the TgNCL1 gene is obviously reduced, and the pathogenicity is obviously reduced; the mouse infected with the TgNCL1 gene deletion strain is neither diseased nor dead, and has high safety to a host. After a mouse is immunized by the toxoplasma gondii attenuated strain with deletion of the TgNCL1 gene, a relatively high humoral immunity and cellular immunity antibody level is generated, a remarkable immune protection effect can be provided for reinfection of high-dose RH, PYS tachyzoites and Pru cysts, and reinfection of toxoplasma gondii can be prevented.