Meningococcus vaccine

A meningococcal and vaccine technology, which is applied in the direction of antibacterial drugs, medical preparations with non-active ingredients, carrier-bound antigen/hapten components, etc., can solve problems that do not involve joint effects, and achieve enhanced specific immune responses, The effect of reducing the cost of vaccines and improving the effect of immunity

Inactive Publication Date: 2012-07-11
NAT VACCINE & SERUM INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of these documents involve chemical conjugates of meningococcal capsular polysaccharides and carrier proteins alone with oligodeoxynucleotides (the oligodeoxynucleotides) containing at least one unmethylated CpG dinucleotide. The combined effect of the first adjuvant with a length of 15-35 nucleotides)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1. CpG-ODN can enhance the immune response of mice to the chemical conjugate of group A meningococcal capsular polysaccharide and tetanus toxoid

[0038] The chemistry of preparing group A meningococcal capsular polysaccharide and group A meningococcal capsular polysaccharide and tetanus toxoid according to the method described in patent document CN101007167A (see Example 1 and Example 4 on pages 9-12 of the specification) Conjugate (hereinafter referred to as "Ag"). In the chemical conjugate, the polysaccharide content is 106 μg / ml, and the carrier protein content is 269 μg / ml.

[0039] The CpG-ODN used in this example was designed by the inventors, and the sequence is as follows: 5'-TCGTTCGTTCGTTCGTTCGTT-3', artificially synthesized by Shanghai Shenggong Biotechnology Company, and subjected to full chain thio modification, polyacrylamide gel electrophoresis (PAGE) Purified, dissolved in physiological saline, stored in a refrigerator at -20℃ for later use.

[0040] ...

Embodiment 2

[0047] Example 2. CpG-ODN can enhance the persistence of mice immune response to the chemical conjugate of group A meningococcal capsular polysaccharide and tetanus toxoid

[0048] The Balb / c mice were immunized according to the same method as in Example 1, and then the meningococcal capsular polysaccharide specific IgG antibody titers were detected to evaluate the effect of CpG-ODN on group A meningococcal capsular polysaccharide in mice The difference between the chemical conjugate and the tetanus toxoid chemical conjugate on the durability of the immune response is that the same method is used to boost the immunization in the 4th week and 39th week after the initial immunization, and the 4th and 6th week after the initial immunization The blood was collected at week, week 10, week 14, week 21, week 39, and week 41, respectively, and the serum was separated, and the meningococcal polysaccharide-specific IgG total antibody was detected according to the method described in Example...

Embodiment 3

[0050] Example 3. CpG-ODN can reduce the amount of chemical conjugate of group A meningococcal capsular polysaccharide and tetanus toxoid

[0051] The Balb / c mice were immunized according to the same method as in Example 1, and then the meningococcal capsular polysaccharide specific IgG antibody titer was detected to determine the effect of CpG-ODN on the group A meningococcal capsular polysaccharide and tetanus The difference in the amount of chemical conjugate of toxin is that the amount of meningococcal capsular polysaccharide and the chemical conjugate of tetanus toxoid are different, and the dosage is the original double dose (2.2μg Ag / mouse ), quarter dose (0.55μg Ag / mouse) and one sixteenth dose (0.14μg Ag / mouse). See the result Figure 3a with Figure 3b .

[0052] Figure 3a with Figure 3b The results shown are the polysaccharide-specific IgG antibody titers at the 4th week after the initial immunization and the second week after the booster immunization. It can be seen...

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Abstract

The invention relates to a meningococcus vaccine comprising a chemical conjugate of meningococcus capsular polysaccharide and carrier protein, and a first adjuvant, wherein the first adjuvant is oligodeoxynucleotide comprising at least one non-methylation CpG dinucleotide, and the length of the oligodeoxynucleotide is 15-35 ribonucleotides. The adjuvant used for increasing the immunization effectof the meningococcus vaccine is a novel human vaccine adjuvant with favorable potential application prospect, and the chemical essence of the adjuvant is the oligodeoxynucleotide which is synthesizedmanually and contains the CpG dinucleotide. By a receptor TLR9 activated immune system on immune cells, the adjuvant reinforces specific immune response aiming at vaccine antigens. The immunization effect of a vaccine can be increased by adding the vaccine adjuvant into the vaccine, so that the dosage of the vaccine antigen can be reduced, the immunization injection times can be reduced and the vaccine cost can be reduced.

Description

Technical field [0001] The present invention relates to the field of biopharmaceuticals. Specifically, the present invention relates to a meningococcal vaccine. Background technique [0002] Meningococcal meningitis (referred to as "meningococcal") is caused by meningococcus and is one of the main acute respiratory infections in humans. According to the chemical structure of capsular polysaccharides, meningococci can be divided into more than ten serogroups, of which A, B, C, Y and W135 are the most prevalent bacterial groups. Vaccination is the main way to prevent meningitis. Vaccines prepared with meningococcal capsular polysaccharides have a certain preventive effect, but it is a T cell-independent antigen, which has poor immune effect on infants under 2 years of age and cannot induce immune memory. Coupling with carrier protein can transform polysaccharide antigens into T cell-dependent antigens, which is not only effective for infants and young children, but also induces i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/39A61K39/095A61K47/48A61P31/04A61K39/385
Inventor 许洪林王潇潇
Owner NAT VACCINE & SERUM INST
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