Relyveld E H, Bizzini B, Gupta R K
Institut Pasteur, Marnes-la-Coquette, France.
Vaccine. 1998 May-Jun;16(9-10):1016-23. doi: 10.1016/s0264-410x(97)00288-0.
Adverse reactions to routine vaccines are obstacles to the mass vaccination campaigns. Though the absolute safety of any injectable vaccine cannot be guaranteed, the adverse side effects to vaccines can be minimized by practicing existing scientific knowledge. Adverse side effects to tetanus and diphtheria toxoids have been known for many years and there have been ways to minimize these reactions. These procedures did not get wide acceptance, because the current partially purified tetanus and diphtheria vaccines meet the regulatory requirements and the manufacturers are reluctant to change the established procedures of production due to the amount of work involved in the regulatory issues under the current Good Manufacturing Practices (GMP). Due to the recent epidemic of diphtheria in the independent states of the former Soviet Union, and its potential for spread to other European Countries, vaccination campaigns with tetanus and diphtheria vaccines received a new boost with several international agencies. In this report, we review the causes for adverse reactions to tetanus and diphtheria vaccines and offer practical suggestions for minimizing these reactions. The major issues in minimizing adverse reactions to these vaccines include: (1) purifying the toxins before detoxification as the reactogenic accessory antigens get covalently bound to the toxins during detoxification; (2) either using well-tolerated adjuvants which do not elicit the production of antigenic specific IgE antibodies responsible for adverse reactions or by using non-adjuvanted highly immunogenic polymerized antigens; (3) checking the status of immunity by recently developed rapid serological methods or by the Schick skin-test for diphtheria to avoid allergic or Arthus-type reactions. These approaches are applicable to industrial scales and would result in a pure, less reactogenic and better characterized toxoids antigens which would be more suitable for combined vaccines comprising highly purified acellular pertussis components, polysaccharide-protein conjugates and other antigens.
常规疫苗的不良反应是大规模疫苗接种运动的障碍。尽管无法保证任何注射用疫苗的绝对安全性，但通过运用现有科学知识可将疫苗的不良副作用降至最低。破伤风和白喉类毒素的不良副作用已为人所知多年，并且已有将这些反应降至最低的方法。这些程序未得到广泛接受，因为当前部分纯化的破伤风和白喉疫苗符合监管要求，而且由于现行良好生产规范（GMP）下监管问题涉及的工作量，制造商不愿改变既定的生产程序。由于前苏联独立国家近期爆发白喉疫情及其向其他欧洲国家传播的可能性，破伤风和白喉疫苗的接种运动在几个国际机构的推动下得到了新的助力。在本报告中，我们回顾了破伤风和白喉疫苗不良反应的原因，并提供了将这些反应降至最低的实用建议。将这些疫苗不良反应降至最低的主要问题包括：（1）在解毒前纯化毒素，因为反应原性辅助抗原在解毒过程中会与毒素共价结合；（2）要么使用耐受性良好、不会引发导致不良反应的抗原特异性IgE抗体产生的佐剂，要么使用无佐剂的高免疫原性聚合抗原；（3）通过最近开发的快速血清学方法或白喉锡克皮肤试验检查免疫状态，以避免过敏或阿瑟斯型反应。这些方法适用于工业规模，将产生更纯、反应原性更低且特性更明确的类毒素抗原，更适合包含高度纯化的无细胞百日咳成分、多糖 - 蛋白质偶联物和其他抗原的联合疫苗。
