49 results about "Attenuated strain" patented technology

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 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 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 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 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 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.

This invention relates to the field of veterinary biological products, specifically to a live attenuated strain of Brucella brucellosis RB39, its applications, vaccines, antigens, and kits. The live attenuated Brucella brucellosis RB39 of this invention can be used to prepare a highly safe vaccine that can be injected into pregnant animals and provides good immunoprotection. Furthermore, this vaccine is suitable for immunization of multiple animal species. In addition, based on the live attenuated Brucella brucellosis RB39 of this invention, an antigen can be prepared to identify Brucella brucellosis antibodies, effectively distinguishing between vaccine immunization and natural infection, providing a scientific basis for brucellosis prevention and control.

The invention discloses a brucella attenuated strain and application thereof in preparation of a vaccine, and belongs to the technical field of virus attenuation. The invention aims to solve the technical problems of weakening the virulence of Brucella and screening and preparing new attenuated vaccines. The invention provides a brucella attenuated strain, which is obtained by taking brucella as a female parent strain and mutating a gene as shown in SEQ ID NO.11 in the female parent strain. The invention lays a foundation for subsequent novel engineering vaccines.

The invention relates to a primer and a TaqMan-MGB probe group for fluorescent quantitative PCR (Polymerase Chain Reaction) detection of virulent and attenuated strains of classical waterfowl parvovirus, the primer and the TaqMan-MGB probe group comprise a fluorescent quantitative PCR detection primer and a probe group for virulent and attenuated strains of goose parvovirus respectively, and the sequences of the primer and the probe group are shown as SEQ ID NO.1-5 respectively; the primer and the TaqMan-MGB probe group further comprise a fluorescent quantitative PCR detection primer and a probe group for virulent and attenuated muscovy duck parvovirus respectively, and the sequences of the primer and the probe group are shown as SEQ ID NO.6-9 respectively. According to the invention, through systematic test verification and reaction condition optimization, an optimal primer-probe combination is screened out, a GPV TaqMan-MGB dual fluorescent quantitative PCR detection method and an MDPV TaqMan dual fluorescent quantitative PCR detection method are respectively and successfully established, and the detection of virulent and attenuated classical waterfowl parvovirus is realized.

The invention discloses a method for carrying out low endotoxin transformation on salmonella choleraesuis and application of the method, and relates to the field of vaccine.Lipid A of a salmonella choleraesuis attenuated strain SC014 is modified through a genetic engineering technology, low endotoxin transformation is carried out on the salmonella choleraesuis, and a salmonella choleraesuis mutant with low endotoxin is successfully constructed. The modified salmonella choleraesuis and the outer membrane vesicle thereof can effectively activate immune response while obviously reducing the activity of endotoxin, so that the safety and the effectiveness are both considered, and a new thought and a new method are provided for developing a novel vaccine.

The invention discloses construction and application of a candida albicans attenuated strain with deletion of a PRO2 gene, and belongs to the technical field of genetic engineering, and the candida albicans attenuated strain is a candida albicans PRO2 deleted strain without expression of the PRO2 gene. The invention further discloses application of the candida albicans attenuated strain with the deletion of the PRO2 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 PRO2 gene in virulence regulation, and a new medicament and a new direction are provided for drugs for treating candida albicans infection.

The application discloses a novel Kdo-MPLA adjuvant, relates to the technical field of synthetic biology, and discloses that the adjuvant is composed of monophosphoryl lipid A (MPLA) and Kdo sugar through an alpha-glycosidic bond, the MPLA is a structure of Salmonella lipid A modified by monophosphorylation at a 4' position, and the Kdo sugar is endowed with amphiphilicity, so that the Kdo sugar is self-assembled into a liposome nanoparticle in an aqueous solution; the attenuated strain of Salmonella is edited by double knockout of rfaC and eptA genes: the rfaC knockout blocks the synthesis of LPS core polysaccharide and retains the lipid A-Kdo connection; the eptA knockout obtains monophosphorylated lipid A; after fermentation of the engineering bacteria, high-purity Kdo-MPLA is obtained by using a phenol-chloroform-petroleum ether extraction method, the process is simplified, and the product is uniform; the adjuvant can activate a TLR4 signal pathway and induce a Th1 type immune response, and the levels of inflammatory factors IL-6 and IL-1beta are significantly lower than those of natural LPS, so that the adjuvant is suitable for a mixed preparation of HPV, malaria and other vaccine antigens; and the application overcomes the uncontrollability of hydrolysis and the high cost defect of chemical synthesis of a traditional MPLA chemical extraction process.

The invention relates to the technical field of genetic engineering, in particular to a pasteurella multocida waaF gene and application thereof in attenuated live vaccines. The sequence of the pasteurella multocida waaF gene is as shown in SEQ ID NO: 1, and a delta waaF gene mutant strain is highly attenuated on ducks, has a certain in-vivo colonization level and has the potential of attenuated live vaccines. The mutant strain is immunized through oral administration and intramuscular injection, so that the production performance of ducks cannot be influenced, and 81.25% and 75% of immune protection can be provided for attacking toxic substances in the lethal dose of pasteurella multocida respectively. Compared with a delta grcA attenuated strain reported in the prior art, the delta waaF mutant strain shows higher-amplitude toxicity reduction, and shows more excellent safety and balanced immune effect only at the cost of a slightly low immune protection rate.

The invention belongs to the technical field of gene engineering, and particularly relates to a toxoplasma gondii attenuated strain as well as a construction method and application thereof. The invention relates to a construction method of a toxoplasma gondii DDX6 gene deleted strain. The toxoplasma gondii DDX6 gene deleted strain is obtained by knocking out a TgDDX6 gene. Wherein the sequence of the TgDDX6 gene is Gene ID: TGGT1313010, and the updating date of the TgDDX6 gene is November 5, 2020. The delta DDX6 immunization has a remarkable immune protection effect on bad pregnancy caused by toxoplasma gondii infection during pregnancy, and can maintain normal states of uterus and placenta to a certain extent, promote normal development of a fetus, reduce the stillbirth rate and relieve negative effects of toxoplasma gondii infection on the pregnancy process and the fetus; a good protection effect is also achieved on acute and chronic toxoplasma gondii infection.

The application relates to a method for improving the yield of attenuated Listeria monocytogenes membrane vesicles and application, wherein, starting from attenuated Listeria monocytogenes LIDeltaAplcB, an LIDeltaAplcBdaldat attenuated strain with dal and dat genes knocked out is constructed, a back-supplement plasmid pCW633 carrying the dal gene is constructed, and the plasmid is electroporated into the attenuated auxotrophic strain LIDeltaAplcBdaldat to construct a stable recombinant strain LIDeltaAplcBdaldat::pCW633. Compared with the wild strain LI, the yield of MVs secreted by the recombinant strain LIDeltaAplcBdaldat::pCW633 can be increased by 1.84 times, and the shape structure, particle size and protein component of the MVs secreted by the recombinant strain are not obviously different from those of the MVs secreted by the wild strain.

This invention belongs to the field of biological control of plant diseases, specifically relating to a virulent strain of *Botrytis cinerea* SdBd-6 and its applications. The virulent strain of *Botrytis cinerea* SdBd-6 is classified and named... Botryosphaeria dothidea The attenuated strain SdBd-6 of Staphylococcus aureus was deposited at the Guangdong Provincial Center for Microbial Culture Collection on January 14, 2026, with accession number GDMCC: 67656. Walsa money The growth of the fungus has a certain inhibitory function. At the same time, after 10 generations of continuous inoculation, the virus contained in the attenuated strain SdBd-6 of *Botrytis cinerea* was not lost, and its growth characteristics and pathogenicity remained attenuated strain characteristics. This provides materials and lays the foundation for the green control of plant fungal diseases caused by the pathogenic fungus *Botrytis cinerea*.

The application discloses a recombinant pseudorabies virus strain expressing classical swine fever virus (CSFV) recombinant E2 protein and application, and relates to the technical field of biology.The TK / gE double gene deletion PRV attenuated strain is used as a virus carrier, an exogenous CSFV E2 gene with a transmembrane region removed is inserted after a PRV gC signal peptide sequence, and a recombinant virus rPRV-delTK / gE-gC-E2 for expressing the gC N terminal and fusing with the PRV gC is constructed; Western blotting analysis and indirect immunofluorescence detection prove that the gC-E2 protein is successfully expressed.The recombinant virus immunized mice can produce specific antibodies against E2; after immunizing piglets, the piglets can produce an antibody level equivalent to that of a classical CSFV attenuated vaccine strain C strain.The rPRV-delTK / gE-gC-E2 obtained in the research is a promising bivalent live vaccine candidate strain.

The invention relates to the field of biotechnology and biological products, in particular to a bordetella bronchiseptica attenuated strain and application thereof. The bordetella bronchiseptica low virulent strain which is remarkably weakened in virulence and keeps high immunogenicity is obtained in a continuous passage and genome sequencing mode, the remarkable virulence weakening characteristic is shown, dog diseases cannot be caused, and the high immunogenicity is achieved. The low virulent strain is used for preparing a bordetella bronchiseptica vaccine, can efficiently stimulate the specific immune response of dog and cat organisms, reduces the repeated inoculation frequency, and avoids the environmental transmission risk of toxic strains from the source. The screened Bordetella bronchiseptica attenuated strain does not contain any exogenous nucleic acid, the genetic background of the strain is clear and traceable, the biological safety requirement of veterinary vaccines is completely met, and a safe and reliable brand-new scheme is provided for dog and cat health protection.