Explore The Adjuvant Effects Of Novel Vaccine Adjuvants Sebacic Acid And S-2-Hydroxyglutaric Acid

Adjuvants are used in vaccines to increase the body's immune response to antigens and also to change the type of immune response.Since adjuvants were discovered in the early 20th century,adjuvants have been used to improve and enhance the vaccine's immune response to the body,such as aluminum adjuvants.However,aluminum adjuvants are not suitable for recombinant proteins and subunit vaccines and may also cause adverse reactions such as inflammation,local erythema,granulomas,subcutaneous nodules,contact dermatitis,IgE-mediated hypersensitivity,and aluminum adjuvants.Aluminum adjuvants cannot induce cytotoxic T cell responses.At present,although there are already a large number of new vaccine adjuvants in research and clinical trials,but very few adjuvants are actually approved for human vaccines.Therefore,the development of new vaccine adjuvants plays an important role in the development of vaccines.The purpose of this experiment was to investigate the effect of azelaic acid and(2S)-hydroxyglutaric acid disodium salt as adjuvants on the humoral immune responses induced by live hepatitis A virus attenuated live vaccine in order to evaluate their adjuvant effects.Azelaic acid is a compound molecule with multiple activities.It has anti-inflammatory,anti-infective and antibacterial effects.Azelaic acid has been widely used in the treatment of acne,melanoma,chloasma,rosacea,hyperpigmentation and sclerosis.Clinical studies have confirmed that Azelaic acid is safe.It has few side effects,no teratogenicity,no systemic adverse reactions,is well tolerated by patients,and does not exhibit bacterial resistance.It is speculated that it has a potentia adjuvant effect.(2S)-Hydroxyglutaric acid Disodium Salt which is easily soluble in the water is a sodium salt and its related studies are less reported.It can reacts with acid to produce 2-hydroxyglutaric acid.They have a similar structure.The current research of(2S)-hydroxyglutaric acid disodium salt shows that it is related to the occurrence of tumor diseases.The widely used traditional Chinese medicine,arsenic,it can fight poison.Although improper use of arsenic can have unpredictable consequences,it can directly threaten daily life.Arsenic,which is arsenic trioxide,is commonly known as arsenic or cremation stone and has the functions of killing bacteria,protozoa,and spirochetes.It also has functions such as erosion,worm killing,robbers,and cutting of malaria.It is used for acne,warts,sores,acne,cold asthma,malaria,dysentery and other diseases.Modern medical research shows that it is effective for the acute promyelocytic leukemia,and can also be used for the treatment of solid tumors such as liver cancer.Arsenic was used as as a reference.We guessed that(2S)-hydroxyglutaric acid disodium salt has an adjuvant effect.The ICR mice were injected respectively with HepA-1(18EU)and AI(OH)3(300?g)and four different doses(0.5mg,lmg,2mg,3mg)of azelaic acid as adjuvant group,300?L for each and one immunization.At the same time,set up the blank group,pure vaccine group,aluminum adjuvant control group.The sera from tail vein blood of mice were collected at the end of 4,8,12 and 16 weeks after immunization and the specific IgG antibody against HAV were detected by indirect ELISA method.In the experiment,The ICR mice were injected respectively with HepA-1(18EU)and AI(OH)3(300?g)and four different doses(0.03mg,0.06mg,0.12mg,0.24mg)of(2S)-hydroxyglutaric acid disodium salt as test group,300?L for each and one immunization.Meanwhile,we set up the blank group,pure vaccine group,aluminum adjuvant control group.The sera from tail vein blood of mice were collected at the end of 4,8,12 and 16 weeks after immunization and the specific IgG antibody against HAV were detected by indirect ELISA method.Through out the experimental period,the mice's health status and diet were observed.At the end of the experiment,the heart,liver,spleen,lungs of the negative control group and the best adjuvant group mice were taken.These organs were made pathological sections for comparison.Azelaic acid and(2S)-hydroxyglutaric acid disodium salt was hypothesized as adjuvants for live hepatitis A virus attenuated live vaccine.The experimental results show that both azelaic acid and(2S)-hydroxyglutaric acid disodium salt have an adjuvant effect.In our study,the adjuvant effect of(2S)-hydroxyglutaric acid disodium salt was even better than the classical,widely used aluminum adjuvant.In the safety test of azelaic acid and(2S)-hydroxyglutaric acid disodium salt,the mice were not found contracture,erect hair,nasal discharge,convulsions,weight loss,and death.No obvious pathological changes were observed in the pathological analysis of heart,liver,spleen,lung,and kidney of the best dose group of azelaic acid and negative control mice.Similarly,no obvious pathological changes were observed in histopathological analysis of heart,liver,spleen,lung,and kidney in the optimal dose group of(2S)-hydroxyglutaric acid disodium salt and negative control mice.It was shown that sebacic acid and(2S)-hydroxyglutaric acid disodium salt have good safety as adjuvants.