There are a number of specific characteristics to be considered when developing and manufacturing vaccines. This article discusses specific requirements to be fulfilled for three attenuated live bacterial vaccines (LBVs) including Mycobacterium bovis BCG vaccine against tuberculosis, Salmonella typhi Ty21a vaccine against typhoid fever, and Vibrio cholerae CVD 103-HgR vaccine against cholera. Special characteristics for these vaccines comprise the appropriate level of attenuation, the balance between safety and immunogenicity, the genetic stability of the organisms combined with environmental risk assessment, the challenge of old-fashioned upstream and downstream methods in combination with quality control of the final product, and the release requirements.
To date, vaccines based on three different technologies are registered for human use: (1) whole inactivated vaccines containing entire killed bacteria or viruses, (2) subunit vaccines, containing only the relevant antigens of the pathogens in a highly purified form, and (3) live attenuated vaccines. The quality and safety requirements are even higher for live attenuated vaccines than for the killed and subunit vaccines. In this article, we will describe how vaccine developers and manufacturers solve the challenges related to manufacturing live attenuated vaccines.
Live Attenuated Vaccines
Live attenuated vaccines are among the most widely used vaccination technologies. Attenuated vaccines consist of bacterial or viral strains, which are weakened by stable mutations that allow the bacteria or viruses to infect humans only transiently. This transient infection elicits immune responses, while the vaccine strains are designed in such a way that they will not cause the symptoms of natural infection by the wildtype pathogen. There are a number of advantages of live attenuated vaccines in comparison to killed and subunit vaccines: (a) they mimic natural infection, therefore eliciting immune responses that are highly specific, effective, and long-lasting (b) they can prevent infection by the pathogen, not just disease symptoms, (c) in comparison to highly purified subunit vaccines, they are relatively cheap to produce and administer, and do not require sophisticated downstream processing or formulation with adjuvants, and (d) several live attenuated vaccines can be administered orally, which has a higher acceptance and better safety profile than injection with syringe and needle, and mimics natural infection better.