Analysis of physicochemical characteristics and component compatibility of diphtheria, tetanus, acellular component pertussis, Sabin inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine
10.13200/j.cnki.cjb.004714
- VernacularTitle:吸附组分无细胞百白破-Sabin株灭活脊髓灰质炎/b型流感嗜血杆菌联合疫苗的理化特征及组分相容性分析
- Author:
Lukui CAI
- Publication Type:Journal Article
- Keywords:
Diphtheria,tetanus,acellular component pertussis,Sabin inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine(DTacP-sIPV/Hib);
Physicochemical characteristics;
Potency;
Humoral immunity;
Component compatibility
- From:
Chinese Journal of Biologicals
2026;39(06):649-658+666
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the physicochemical characteristics and component compatibility of diphtheria,tetanus,acellular component pertussis,Sabin inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine(DTacP-sIPV/Hib),in order to provide data support for preclinical research of DTacP-sIPV/Hib vaccine.Methods DTacP-sIPV/Hib was prepared using the diphtheria,tetanus,acellular component pertussis,Sabin inactivated poliovirus vaccine(DTacP-sIPV)to reconstitute the lyophilized Haemophilus influenzae type b conjugate vaccine(Hib).The pH,particle size,Zeta potential,and osmotic pressure of the vaccine were measured at 5 min,30 min,1 h,3 h,and 6 h after reconstitution,and the morphology of the vaccine was observed under a microscope.Forty Wistar rats were randomly divided into four groups including separate injection,mixed injection immediately,injection 1 h after mixing and injection 6 h after mixing,with 10 rats in each group,half male and half female.All rats were injected intramuscularly once every four weeks for a total of three doses.The blood samples were collected from the tail vein before administration and 28 days after each administration to separate the serum.The antibody titers against diphtheria toxoid(DT),tetanus toxoid(TT),pertussis toxin(PT),filamentous hemagglutinin(FHA),pertactin(PRN) and polyribosylribitol phosphate(PRP) in rat serum were detected by ELISA.The neutralizing antibody titers against type Ⅰ poliovirus(PV Ⅰ),PV Ⅱ and PV Ⅲ were detected by microneutralization test method and the geometric mean titer(GMT) and antibody positive rate of each antibody were calculated.Seventy-two Wistar rats were randomly divided into single-component vaccines(DT,TT,PT,FHA,PRN,Hib,sIPV,sIPV Ⅱ,and sIPV Ⅲvaccines with aluminum adjuvant;Hib vaccine without adjuvant),DTacP-sIPV,and DTacP-sIPV/Hib groups,with six rats in each group,half males and half females.The immunization route,frequency,detection time point and detection method were the same as above.The vaccine potency before and after the combination of DTacP-sIPV and Hib vaccines was detected according to the method specified in the Chinese Pharmacopoeia(Volume III,2020 edition).Results The pH value,Zeta potential,particle size,and appearance of the DTacP-sIPV/Hib vaccine remained stable 6 hours after reconstitution,and the osmotic pressure slightly increased.Compared with the separate injection group,the GMTs and positive conversion rates of antibodies against DT,TT,PT,FHA,PRN,PRP,PVⅠ,PVⅡ,and PVⅢ in the serum of rats in the immediate injection,1 h and 6 h groups were not statistically different(F = 0.37-4.69,each P > 0.05).Compared with the single-component vaccine and DTacP-sIPV groups,the GMTs of antibodies against DT,TT,and FHA in the serum of rats in the DTacP-sIPV/Hib group were not statistically different(F = 0.17-2.44,each P > 0.05).The GMTs of antibodies against PT,PRN,PVⅠ,PVⅡand PVⅢ were significantly lower than those of the single component vaccine groups(F = 5.38-20.01,each P < 0.05),while exhibited no statistical significance compared with the DTacP-sIPV group(F = 5.38-20.01,each P > 0.05).The GMT of anti-PRP antibody was significantly higher than that of the Hib group without aluminum adjuvant(F = 7.19,P < 0.05),while compared with the Hib group with aluminum adjuvant,the difference was not statistically significant(F = 7.19,P > 0.05).The seroconversion rates of antibodies against DT,TT,PT,FHA,PRN,PRP,PVⅠ,PVⅡ,and PVⅢ in the DTacP-sIPV/Hib group were 100%,which were the same as those in the single-component vaccine and DTacP-sIPV groups.The titers of diph-theria,tetanus,pertussis,poliomyelitis,and Hib vaccines before and after mixing all met the requirements of the Chinese Pharmacopoeia(Volume III,2020 edition),and the difference was small.Conclusion Before and after the reconstitution of Hib with DTacP-sIPV,there were no significant changes in the physicochemical properties,immunogenicity,and potency of the vaccine,indicating a good compatibility between the antigen components.
