BERNA: a century of immunobiological innovation.

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.