ABSTRACT

Vaccines are among the most successful and cost-effective public health interventions ever devised. Up until the 1980s, most viral vaccines were based on attenuated or inactivated pathogens. While these traditional vaccine technologies enabled the production of vaccines for many diseases, both approaches have limitations that are signicant barriers to vaccine development and implementation in the current regulatory climate. Attenuated vaccines have the potential to revert to more virulent forms and are also contraindicated in immunodecient individuals. The process of pathogen inactivation, particularly when using chemical agents, may alter the structure of the virus, affecting the quality of the immune response, as exemplied by the inactivated RSV vaccine candidate introduced in the 1960s that made vaccinated individuals more susceptible to disease-related pathology [1]. The advent of recombinant techniques allowed the preparation of subunit vaccines that consist of isolated antigens. Subunit vaccines generally have good safety proles, but vaccines based on individual proteins or peptides are far less effective than whole virus preparations. In particular, subunit vaccines generally do not have the highly multivalent, repetitive structure that is characteristic of highly immunogenic antigens. Thus, subunit vaccines are typically poorly immunogenic; they require more frequent and larger doses of antigen in combination with potent adjuvants. In addition, the immune responses elicited by subunit vaccines are typically

short lived, meaning that booster immunizations are often required in order to maintain optimal protection.