Cryz S J
BERNA, Swiss Serum and Vaccine Institute Berne, Rehhagstrasse 79, CH-3018, Bern, Switzerland.
Vaccine. 1999 Oct 1;17 Suppl 2:S1-5. doi: 10.1016/s0264-410x(99)00228-5.
At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic, when administered by the intranasal route.
1898年瑞士伯尔尼血清与疫苗研究所（BERNA）成立之时，可用的疫苗或免疫球蛋白寥寥无几。这一简短清单包括霍乱、伤寒、鼠疫、天花和狂犬病疫苗以及马抗破伤风和白喉免疫球蛋白。此外，由于生产能力有限、安全性不确定且缺乏促进其使用的公共卫生基础设施，它们的使用受到限制。如今，有超过30种传染病有安全有效的疫苗，同时有人类高效价免疫球蛋白用于治疗或预防狂犬病、破伤风、呼吸道合胞病毒、巨细胞病毒、甲型肝炎、乙型肝炎和疱疹病毒（水痘带状疱疹病毒）感染。在其存在的100年里，BERNA通过引入导致更安全、更有效疫苗的新技术，在该领域的发展中发挥了关键作用。它是冻干无细菌污染天花疫苗研发的先驱。伤寒杆菌Ty21a伤寒疫苗株表明，针对肠道细菌病原体的口服免疫不仅可行，而且几乎不会伴随不良反应。这一发现推动了其他减毒活菌株的研发，这些菌株不仅可作为疫苗，还可作为疫苗抗原和基因治疗的载体。一个这样的例子是霍乱弧菌CVD 103-HgR，这是第一种通过重组DNA技术获得的供人类使用的活疫苗。后续研究表明，这两种疫苗株可以联合使用而不牺牲安全性或免疫原性，为联合口服疫苗奠定了基础。最近，一种名为病毒体的新型疫苗抗原递送系统已被用于构建甲型肝炎和流感疫苗。此类疫苗引起的局部不良反应比传统疫苗少，且免疫原性增强。病毒体配制的流感疫苗经鼻内给药时也已证明是安全且具有免疫原性的。
