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Objective@#To evaluate the immune persistence following intradermal(ID) vaccination with diphtheria-tetanusacellular component pertussis and Sabin-derived inactivated poliovirus vaccine(DTacP-sIPV).@*Methods@#40 wistar rats were randomly assigned into four groups.Two test groups were injected intradermally with fractional-doses(1/5 and 1/10dose) of DTacP-sIPV(1/5D ID and 1/10D ID group);The positive control group was intramuscularly injected with full dose of DTacP-sIPV(full-dose IM group);The negative control group was injected with PBS intradermally.Wistar rats were immunized 3 times at 0,1 and 2 months and the blood samples were collected via tail vein 12 months after the last immunization and the serum samples were isolated.The titer of neutralizing antibody against poliovirus was detected by micro-neutralization test,and the titers of IgG antibodies against diphtheria toxin(DT),tetanus toxin(TT),pertussis toxin(PT),filamentous hemagglutinin(FHA) and pertactin(PRN) in rat serum were detected by indirect ELISA.The geometric mean titer(GMT)and positive rate of antibody were calculated.The rats were challenged with aerosolized B.pertussis for 30 min 12 months after the last immunization and determined for the white blood cell(WBC) count and colony-forming unit(CFU) in lung,trachea and nose at day 2,5 and 14 after challenge.@*Results@#Compared with the full-dose IM group,there was no significant difference in the positive rates of poliovirus type Ⅰ,Ⅱ and Ⅲ neutralizing antibodies between 1/5D ID and 1/10D ID groups(each P> 0.05) and the positive rates of all types of antibodies in the control group were 0.The positive rates of IgG antibodies against DT,TT,PT,FHA and PRN in 1/5D ID,1/10D ID and full-dose IM groups were all 100%,and those in control group were all 0.Compared with 2 d after challenge,the WBC counts of rats in control group increased significantly 5 d after aerosol challenge with B.pertussis(F=3.48,P <0.05),and then began to decrease,while those in other groups remained stable with time(F=0.14～1.30,P> 0.05).After aerosol challenge,the CFU in lungs of rats in control group was significantly higher than that in the other three groups(F=19.00～206.00,P<0.05),and B.pertussis was still detected 14 d after challenge;Except for the control group,the bacterial load in lungs of rats in the other three groups reached the peak 5d after challenge,the B.pertussis was basically cleared on the 14d,and there was no significant difference among the groups at each time point(F=1.14～1.25,P> 0.05).The bacterial load of trachea and nose in the control group was slightly higher than that in other groups at each time point,but the difference was not significant(F=0.71～3.54,P> 0.05).Except for the control group,the bacterial load in the trachea and nose of the other three groups were similar,and no significant difference was observed(F=0.75～3.41,P>0.05).@*Conclusion@#ID immunization with1/5 dose of DTacP-sIPV induced persistent protective antibodies against various components of the vaccine in rats.This study provided an experimental basis for the formulation of immunization strategy of ID immunization with fractional dose of DTacP-sIPV.
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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.
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Objective@#To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults.@*Methods@#The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose).@*Results@#The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; β (95%CI) was -0.07 (-0.34-0.20), P=0.601.@*Conclusion@#The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.
ABSTRACT
Objective] To evaluate the immune effect of hepatitis B vaccine by different inocula-ting programs for adults as 0-1-3 month, 0-1-6 month and 0-1-12 month and to provide evidence for the development of adult immunization strategy. [ Methods] In Tongxiang City of Zhejiang Province, 10μg of hepatitis B vaccine was voluntarily inoculated by different immunization programs as 0 -1 -3 month, 0-1-6 month or 0 -1 -12 month among adults aged 16 to 49 years.Quantitative detection of anti-HBs was conducted after 1 month and 1 year of immunization, and the positive seroconversion rates and geometric mean titers of anti-HBs ( GMT) were evaluated. [ Results] Totally 682 subjects were evaluated.The anti-HBs positive rates were 99.85% after 1 month of immunization, and 70.23% after 1 year of immunization.It was observed that GMT of anti-HBs was higher with adults of younger age. [ Conclusion] Adults can achieve better immune effect by inoculation of 10μg of hepatitis B vaccine and when it is done in target population according to 0-1-6 month program,compliance is better and immune effect proves more persistent.It is suggested that hepatitis B vaccine should be inoculated for the adults as early as possible to ensure the effect and persistence of the vaccine.