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.

Mucosal immunity can effectively prevent pathogen invasion of the mucosa at the initial stage of infection and inhibit pathogen replication within the body at later stages of infection. Therefore, the development of mucosal vaccines is of great significance for the prevention and control of infectious diseases. Intranasal vaccines can induce cellular, humoral, and mucosal immunity in the nasal mucosa and nasal-associated lymphoid tissue, producing secretory IgA, which plays a crucial role in preventing respiratory infections. However, the dilution of antigens by nasal mucus, clearance of antigens by cilia, and the barrier function of nasal epithelial cells in the nasal cavity can reduce the bioavailability of antigens and limit the efficacy of intranasal vaccines. This article reviews the structure of the nasal mucosal immune system and its mediated immune response, as well as intranasal vaccines that have been launched or are currently in clinical research, and explores the challenges faced in intranasal vaccine research.

Mucosal immunity can effectively prevent pathogen invasion of the mucosa at the initial stage of infection and inhibit pathogen replication within the body at later stages of infection. Therefore, the development of mucosal vaccines is of great significance for the prevention and control of infectious diseases. Intranasal vaccines can induce cellular, humoral, and mucosal immunity in the nasal mucosa and nasal-associated lymphoid tissue, producing secretory IgA, which plays a crucial role in preventing respiratory infections. However, the dilution of antigens by nasal mucus, clearance of antigens by cilia, and the barrier function of nasal epithelial cells in the nasal cavity can reduce the bioavailability of antigens and limit the efficacy of intranasal vaccines. This article reviews the structure of the nasal mucosal immune system and its mediated immune response, as well as intranasal vaccines that have been launched or are currently in clinical research, and explores the challenges faced in intranasal vaccine research.

In recent years, studies have shown that transplanted neural stem cells (NSCs) help neural tissues regenerate and return to normal through paracrine action rather than just replacing cells. Exosomes are essential paracrine mediators that can participate in cell communication through substance transmission. This review focuses on NSCs regulated by exosomes and their application in treatment of nervous system diseases, in order to provide important references for further research and clinical application of NSCs exosomes..

Objective:To evaluate the effects of a booster immunization with a candidate tetanus toxoid, reduced diphtheria toxoid and acellular pertussis combined vaccine (Tdap) in a rat model after primary vaccination with diphtheria, tetanus, acellular pertussis and Sabin strain inactivated poliovirus combined vaccine (DTacP-sIPV) or diphtheria, tetanus, acellular pertussis, inactivated poliovirus and haemophilus type b combined vaccine (DTacP-IPV/Hib) for further preclinical study.Methods:Wistar rats were randomly divided into three groups and respectively immunized with a self-developed DTacP-sIPV, a marketed DTacP-IPV/Hib and normal saline at 0, 1, and 2 months of age. Serum levels of antibody against each component in each group were detected before immunization and after each dose. A booster dose of the candidate Tdap was given 10 months after primary immunization. Serum levels of antibody against each component in each group were detected before, 1 month and 6 months after the booster immunization.Results:One month after three doses of primary immunization, the geometric mean titers (GMT, Log2) of antibodies against diphtheria toxoid (DT), tetanus toxoid (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) in the DTacP-sIPV group were 17.41, 18.34, 18.11, 19.93 and 13.91, respectively, and the seroconversion rates of these components all reached 100%. Ten months after primary immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN decreased to 15.17, 14.26, 13.60, 14.51 and 10.39, respectively, and the seroconversion rates remained above 89%. One month after booster immunization, the GMTs of antibodies against DT, TT, PT and FHA in the DTacP-sIPV and DTacP-IPV/Hib groups were 16.49/17.26, 16.80/17.63, 16.70/17.74 and 18.48/19.26, respectively, and the seroconversion rates of these components all reached 100% with no significant difference between the two groups ( P>0.05). The GMTs of anti-PRN antibody in the DTacP-sIPV and DTacP-IPV/Hib groups were 13.07 and 11.00, and the seroconversion rates were 100% and 88%, which were higher in the DTacP-sIPV group than in the DTacP-IPV/Hib group ( P<0.05). Six months after booster immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN in the DTacP-sIPV and DTacP-IPV/Hib groups decreased to 15.74/14.87, 15.07/15.14, 14.84/15.73, 16.62/16.37 and 11.44/9.96, respectively, and the seroconversion rates remained above 88%. Conclusions:Booster vaccination with the candidate Tdap vaccine induces humoral immune response following primary immunization with DTacP-sIPV or DTacP-IPV/Hib in the Wistar rat model, while the antibody titer decreases with time.