Wistar大鼠皮内免疫Sabin株脊髓灰质炎灭活疫苗的免疫持久性及加强免疫效果研究
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摘要
脊髓灰质炎野毒株消灭后,口服脊髓灰质炎减毒活疫苗(Oral polio vaccine,OPV)将被停止使用,脊髓灰质炎灭活疫苗(Inactivated poliovirus vaccine,IPV)将全面替代OPV,但IPV成本过高,难以满足全球需要。皮内免疫可以降低Sabin株脊髓灰质炎灭活疫苗(Inactivated poliovirus vaccine derived from Sabin strain,sIPV)的免疫剂量,本研究将观察sIPV疫苗皮内免疫大鼠后的免疫持久性及加强免疫效果。本研究采用sIPV,设皮内免疫组、全剂量肌肉免疫组和皮内免疫阴性对照组,接种Wistar大鼠,于3剂基础免疫程序完成后第1个月、12个月采血;第12个月采血后加强免疫1剂,并于加强免疫1个月后采血。中和试验检测各血清抗脊灰病毒中和抗体效价,评价皮内免疫sIPV的免疫持久性及加强免疫效果。Wistar大鼠3剂基础免疫后1个月,1/5、1/3剂量皮内免疫组与全剂量肌肉免疫组Ⅰ、Ⅱ、Ⅲ型抗体阳转率均达到了100%,各型别中和抗体几何平均滴度(Geometric mean titer,GMT)均远高于1∶8保护水平。基础免疫后12个月,sIPV全剂量组各型阳转率均维持在80%以上,1/10剂量皮内免疫组在50%以上,1/5剂量皮内免疫组维持在70%以上,1/3剂量皮内免疫组维持在80%以上,除1/10剂量组Ⅱ型外其余各组各型别GMT均维持在1∶8以上。加强免疫后1个月,1/5剂量皮内免疫组、1/3剂量皮内免疫组及全剂量组的Ⅰ型、Ⅱ型、Ⅲ型各组中和抗体阳转率均达到100%,并能够诱导产生远高于1∶8的抗体水平。本研究结果显示sIPV疫苗皮内免疫具有良好的免疫持久性及加强免疫效果。
After the elimination of wild poliovirus strains, oral polio vaccine( OPV) will be no longer used. Inactivated poliovirus vaccine(IPV) will replace OPV worldwide. However, the cost of IPV is too high to meet the global needs. Intradermal immunization can reduce the dosage of inactivated poliovirus vaccine derived from the Sabin strain(sIPV). To observe the immune persistence and efficacy of boosting dose of sIPV after intradermal immunization in rats, full-dose sIPV given via the intramuscular route was used as control. Experimental and negative-control groups were designed as which were injected with sIPV and saline, respectively, via the intradermal route. Wistar rats in various groups were immunized and blood samples were collected at the first and 12th month after completion of three doses of the basic immunization program. After blood collection at the 12th month post-immunization, one boosting dose was immunized. Blood samples were collected after 1 month of using the boosting dose. Titers of neutralizing antibodies were tested to evaluate the immune persistence and efficacy of a boosting dose of sIPV. One month after a three-dose schedule in Wistar rats, all of the seroconversion rates of types Ⅰ, Ⅱ and Ⅲ of 1/5-dose, 1/3-dose needle-free intradermal group, and full-dose intramuscular group were 100%. The geometric median titers(GMTs) of all three types were much higher than that of the protective titer(1 : 8). Twelve months after the basic immunization, the seroconversion rates of all types were great than 80% in the full-dose sIPV group, great than or equal to 50% in the 1/10-dose intradermal group,great than or equal to 70% in the 1/5-dose intradermal group,and great than or equal to 80% in the 1/3-dose intradermal group. GMTs of all three types were maintained great than 1: 8 in all groups except type Ⅱ in the 1/10-dose intradermal group. One month after the boosting dose, all of the seroconversion rates of types Ⅰ, Ⅱ and Ⅲreached 100% in the 1/5-dose intradermal group, 1/3-dose intradermal group, and full-dose group, respectively. The booster could induce much higher antibody levels than that of the protective titer(1: 8). sIPV with intradermal immunization induced good immune persistence and efficacy of a boosting dose.
After the elimination of wild poliovirus strains, oral polio vaccine( OPV) will be no longer used. Inactivated poliovirus vaccine(IPV) will replace OPV worldwide. However, the cost of IPV is too high to meet the global needs. Intradermal immunization can reduce the dosage of inactivated poliovirus vaccine derived from the Sabin strain(sIPV). To observe the immune persistence and efficacy of boosting dose of sIPV after intradermal immunization in rats, full-dose sIPV given via the intramuscular route was used as control. Experimental and negative-control groups were designed as which were injected with sIPV and saline, respectively, via the intradermal route. Wistar rats in various groups were immunized and blood samples were collected at the first and 12th month after completion of three doses of the basic immunization program. After blood collection at the 12th month post-immunization, one boosting dose was immunized. Blood samples were collected after 1 month of using the boosting dose. Titers of neutralizing antibodies were tested to evaluate the immune persistence and efficacy of a boosting dose of sIPV. One month after a three-dose schedule in Wistar rats, all of the seroconversion rates of types Ⅰ, Ⅱ and Ⅲ of 1/5-dose, 1/3-dose needle-free intradermal group, and full-dose intramuscular group were 100%. The geometric median titers(GMTs) of all three types were much higher than that of the protective titer(1 : 8). Twelve months after the basic immunization, the seroconversion rates of all types were great than 80% in the full-dose sIPV group, great than or equal to 50% in the 1/10-dose intradermal group,great than or equal to 70% in the 1/5-dose intradermal group,and great than or equal to 80% in the 1/3-dose intradermal group. GMTs of all three types were maintained great than 1: 8 in all groups except type Ⅱ in the 1/10-dose intradermal group. One month after the boosting dose, all of the seroconversion rates of types Ⅰ, Ⅱ and Ⅲreached 100% in the 1/5-dose intradermal group, 1/3-dose intradermal group, and full-dose group, respectively. The booster could induce much higher antibody levels than that of the protective titer(1: 8). sIPV with intradermal immunization induced good immune persistence and efficacy of a boosting dose.
引文
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[10] Darius S,Pauline V,Alienke J W,Claire J B,Patrick K, Leo G V, Nynke Y R. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults[J]. Vaccine, 2013, 31:3688-3694.
[11] Li R,Li C G,Li Y,Liu Y,Zhao H,Chen X,Kuriyakose S,Van Der M O,Hardt K,Hezareh M,RoyGhanta S. Primary and booster vaccination with an inactivated poliovirus vaccine(IPV)is immunogenic and welltolerated in infants and toddlers in China[J]. Vaccine,2016, 34:1436-1443.
[2] Jafari H, Deshpande J M, Sutter R W, Bahl S, Verma H, Ahmad M,Kunwar A,Vishwakarma R,Agarwal A,Jain S,Estivariz C,Sethi R, Molodecky N A,Grassly N C, Pallansch M A, Chatterjee A, Aylward BR. Efficacy of inactivated poliovirus vaccine in India[J].Science, 2014, 345(6199):922-925.
[3] Foiadelli T,Savasta S,Battistone A,Kota M,Passera C,Fiore S,Bino S, Amato C,Lozza A,Marseglia L G, Fiore L. Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis[J]. BMC Infect Dis,2016, 16:277.
[4] World Health Organization. Polio vaccines:WHO position paper, March 2016-recommendations[J]. Vaccine,2017, 35(9):1197-1199.
[5]陈海波.我国批准全球首个Sabin株脊髓灰质炎灭活疫苗上市[N].光明日报,2015-01-15(006).CHEN Haibo. The first inactivated poliovirus vaccine derived from Sabin strain in the world has been approved in China[N]. Guangming Daily, 2015-01-15(006).
[6] Improving the affordability of inactivated poliovirus vaccines(IPV)for use in low-and middle-income countries. An economic analysis of strategies to reduce the cost of routine IPV immunization[EB/OL]. PATH,April 20, 2010.
[7] Ma L, Cai W, Sun M, Cun Y, Zhou J, Liu J, Hu W,Zhang X, Song S, Jiang S, Liao G. Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine(sIPV)with intradermal delivery in rats[J].Hum Vaccin Immunother, 2016, 12(12):3125-3131.
[8] Deepa G, Samitha G,Paba P. National introduction of fractional-dose inactivated polio vaccine in Sri Lanka following the global"switch"[J]. WHO South-East Asia Journal of Public Health, 2018, 7(2):79-83.
[9] World Health Organization. Manual for the virological investigation of polio[EB/OL]. WHO/EPI/GEN 97.01,1997.
[10] Darius S,Pauline V,Alienke J W,Claire J B,Patrick K, Leo G V, Nynke Y R. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults[J]. Vaccine, 2013, 31:3688-3694.
[11] Li R,Li C G,Li Y,Liu Y,Zhao H,Chen X,Kuriyakose S,Van Der M O,Hardt K,Hezareh M,RoyGhanta S. Primary and booster vaccination with an inactivated poliovirus vaccine(IPV)is immunogenic and welltolerated in infants and toddlers in China[J]. Vaccine,2016, 34:1436-1443.