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CN-121987769-A - Mycoplasma pneumoniae vaccine and application thereof

CN121987769ACN 121987769 ACN121987769 ACN 121987769ACN-121987769-A

Abstract

The invention provides a mycoplasma pneumoniae vaccine and application thereof. The vaccine composition has a good protection effect on mycoplasma pneumoniae infection, can remarkably reduce weight loss, reduce pulmonary pathogen load and reduce pulmonary pathology scores, and has extremely high application value in mycoplasma pneumoniae vaccine development.

Inventors

  • LI QIANQIAN
  • WANG YOUCHUN
  • HUANG LUXIA
  • XIAO HONGJIAN
  • LI ZHIHUA
  • ZHANG HENG

Assignees

  • 中国医学科学院医学生物学研究所

Dates

Publication Date
20260508
Application Date
20260205

Claims (10)

  1. 1. A vaccine composition comprising at least three proteins or variants thereof selected from the group consisting of CARDS, P1, P40-90, P116 and MPN133; Wherein said CARDS or variant thereof comprises the amino acid sequence shown as any one of SEQ ID NO. 1, 6-10, said P1 or variant thereof comprises the amino acid sequence shown as any one of SEQ ID NO. 2, 11-18, said P40-90 or variant thereof comprises the amino acid sequence shown as any one of SEQ ID NO. 3, 19-20, said P116 or variant thereof comprises the amino acid sequence shown as any one of SEQ ID NO. 4, 21-23, and said MPN133 or variant thereof comprises the amino acid sequence shown as any one of SEQ ID NO. 5 or 24.
  2. 2. The vaccine composition of claim 1, wherein the vaccine composition comprises rds, P116, and MPN133.
  3. 3. Vaccine composition according to claim 2, characterized in that it may further comprise P1 and/or P40-90.
  4. 4. A vaccine composition according to any one of claims 1-3, characterized in that the vaccine composition comprises any one of the following groups: 1-1) CARDS with the amino acid sequence shown in any one of SEQ ID NO 6 and 8-10, P1 with the amino acid sequence shown in any one of SEQ ID NO 11-14 and 16-18, P40-90 with the amino acid sequence shown in SEQ ID NO 19, P116 with the amino acid sequence shown in SEQ ID NO 21-23, MPN133 with the amino acid sequence shown in SEQ ID NO 24; 1-2) CARDS having the amino acid sequence shown in any one of SEQ ID NO. 6-10, P1 having the amino acid sequence shown in any one of SEQ ID NO. 11-14 and 16-18, P40-90 having the amino acid sequence shown in SEQ ID NO. 19-20, P116 having the amino acid sequence shown in SEQ ID NO. 21-23, MPN133 having the amino acid sequence shown in SEQ ID NO. 24; 1-3) CARDS with the amino acid sequence shown in any one of SEQ ID NO 6-8 and 10, P1 with the amino acid sequence shown in any one of SEQ ID NO 11-14, P40-90 with the amino acid sequence shown in SEQ ID NO 20, P116 with the amino acid sequence shown in SEQ ID NO 21 and 22, MPN133 with the amino acid sequence shown in SEQ ID NO 24; 1-4) CARDS as shown in any one of SEQ ID NO. 6, 7 and 10, P1 as shown in any one of SEQ ID NO. 12, P40-90 as shown in SEQ ID NO. 20, P116 as shown in SEQ ID NO. 22, MPN133 as shown in SEQ ID NO. 24, or, 1-5) The amino acid sequence is CARDS shown as SEQ ID NO. 10, the amino acid sequence is P116 shown as SEQ ID NO. 22, and the amino acid sequence is MPN133 shown as SEQ ID NO. 24.
  5. 5. The vaccine composition of claim 4, wherein the vaccine composition comprises CARDS having the amino acid sequence shown in SEQ ID NO. 10, P116 having the amino acid sequence shown in SEQ ID NO. 22, and MPN133 having the amino acid sequence shown in SEQ ID NO. 24.
  6. 6. The vaccine composition of claim 5, wherein the vaccine composition, the vaccine composition further comprises a vaccinologically acceptable carrier; Among them, the vaccine acceptable carrier includes but is not limited to aluminum adjuvant, MF59, freund's complete adjuvant, freund's incomplete adjuvant, cpG adjuvant, BCG nucleic acid, cpG ODN (unmethylated cytosine-guanine dinucleotide oligodeoxynucleotide), cholera toxin B subunit (CTB), escherichia coli heat-labile enterotoxin B subunit (LTB), polyinosinic acid-polycytidylic acid (PolyI: C) or monophosphoryl lipid A.
  7. 7. A nucleic acid molecule encoding a protein or variant thereof as defined in the vaccine composition according to any one of claims 1 to 6, said encoding comprising encoding said protein or variant thereof by means of a nucleic acid molecule or a set of nucleic acid molecules.
  8. 8. Recombinant expression vector, characterized in that it comprises a nucleic acid molecule according to claim 7.
  9. 9. Host cell, characterized in that it expresses a protein as defined in the vaccine composition according to any one of claims 1 to 6 or a variant thereof, or comprises a nucleic acid molecule according to claim 7, or comprises a recombinant expression vector according to claim 8.
  10. 10. A method of preparing a vaccine composition, comprising culturing the host cell of claim 9, and isolating the protein or variant thereof from the culture product to prepare the vaccine composition.

Description

Mycoplasma pneumoniae vaccine and application thereof Technical Field The invention belongs to the technical field of genetic engineering vaccines, and particularly relates to a mycoplasma pneumoniae vaccine and medical application thereof. Background Mycoplasma pneumoniae is a cell wall-free microorganism, a major pathogenic bacterium of atypical pneumonia, and often causes tracheobronchitis and other upper and lower respiratory tract infections. About 70% of patients develop fever, dry cough, rhinitis, sore throat, shortness of breath, etc., severe infections can lead to pulmonary edema, obstructive bronchiolitis, chronic interstitial fibrosis, respiratory distress syndrome, etc., and extrapulmonary symptoms such as nerve, cardiovascular, skin, digestive, blood and musculoskeletal systems, etc. Susceptible people include children under 5 years old, the elderly and immunocompromised persons, and their infections account for 20% -30% of community-acquired pneumonia. Macrolide antibiotics are first-line therapeutic drugs, but Macrolide Resistant Mycoplasma Pneumoniae (MRMP) has become a global public health problem in the past decade, particularly in asia, with a drug resistance rate of 13.6% -100%, and popular seasons in japan and china even more than 90%, so there is a need to enhance new drug development and new preventive measure research, where vaccination can effectively block transmission and reduce infection risk. One of the major hurdles in the development of mycoplasma pneumoniae vaccines in humans is the lack of a defined protective antigen or immune target. The pathogenesis of infection is complex, and the infection involves the approaches of adhesion to host cells, nutrition deprivation injury, invasion, toxin production, cytokine-mediated inflammatory injury, immune escape and the like, and extrapulmonary manifestations are related to direct injury mediated by invasion and inflammatory factors, indirect injury of host immune response and vascular obstruction. Although scientific researchers have developed a large number of vaccine research and development works, mycoplasma pneumoniae vaccines are not available in batches at present due to the challenges of complex pathogenesis of mycoplasma pneumoniae, undefined vaccine targets, risk of vaccine-enhanced diseases and the like. Disclosure of Invention In order to solve the technical problems, CARDS, P1, P40-90, P116 and MPN133 are innovatively selected as templates for segment expression and site-directed mutagenesis to screen effective immune epitopes. Meanwhile, based on a design strategy of bacterial vaccine multi-antigen combined immunization, proteins with strong immunogenicity and protective efficacy are combined, a better combined immunization effect is obtained unexpectedly, and a new idea is developed for mycoplasma pneumoniae vaccine research and development. In a first aspect, the invention provides a vaccine composition. In some embodiments, the vaccine composition comprises at least three proteins or variants thereof selected from the group consisting of CARDS, P1, P40-90, P116, and MPN133; In some embodiments, the CARDS or variant thereof comprises the amino acid sequence set forth in any one of SEQ ID NO. 1, 6-10, the P1 or variant thereof comprises the amino acid sequence set forth in any one of SEQ ID NO. 2, 11-18, the P40-90 or variant thereof comprises the amino acid sequence set forth in any one of SEQ ID NO. 3, 19-20, the P116 or variant thereof comprises the amino acid sequence set forth in any one of SEQ ID NO. 4, 21-23, and the MPN133 or variant thereof comprises the amino acid sequence set forth in any one of SEQ ID NO. 5 or 24. In some embodiments, the vaccine composition comprises CARDS, P116, and MPN133; In some embodiments, the vaccine composition may further comprise P1 and/or P40-90; In some embodiments, the vaccine composition comprises CARDS, P116, P1 and MPN133, in some embodiments, the composition comprises CARDS, P116, P40-90 and MPN133, and in some embodiments, the composition comprises CARDS, P116, P1, P40-90 and MPN133. In some embodiments, the CARDS or variant thereof comprises the amino acid sequence shown as SEQ ID NO. 1, 6-10, the P1 or variant thereof comprises the amino acid sequence shown as SEQ ID NO. 2, 11-18, the P40-90 or variant thereof comprises the amino acid sequence shown as SEQ ID NO. 3, 19-20, the P116 or variant thereof comprises the amino acid sequence shown as SEQ ID NO. 4, 21-23, and the MPN133 or variant thereof comprises the amino acid sequences shown as SEQ ID NO. 5 and 24. In some embodiments, the vaccine composition comprises any one of the following groups: 1-1) CARDS with the amino acid sequence shown in any one of SEQ ID NO 6 and 8-10, P1 with the amino acid sequence shown in any one of SEQ ID NO 11-14 and 16-18, P40-90 with the amino acid sequence shown in SEQ ID NO 19, P116 with the amino acid sequence shown in SEQ ID NO 21-23, MPN133 with the amino acid sequence shown in SEQ