Vaccine technology specific considerations
In the field of vaccinology, new technological platforms have emerged, each with specific challenges for development. Two classical vaccine products stay close to the original pathogen, either as an inactivated or a modified live version that causes no disease. There are several examples of attenuated and inactivated vaccines against viral diseases (e.g. MMR and IPV), whereas there are fewer examples for bacterial pathogens. BCG is a rare example of marketed live attenuated vaccine and whole-cell pertussis is one of the few inactivated vaccines. For TB, recombinant BCG and live attenuated M. tuberculosis candidates are in advanced stages of clinical development.
Subunit vaccines combine pathogen-specific antigens with an adjuvant as a supportive immunostimulant. Examples are the Hepatitis B subunit vaccine, bacterial toxoid vaccines e.g. Tetanus and Diphtheria, and conjugate vaccines e.g. pneumococcal vaccines. For TB, single recombinant polypeptide antigens and multiple, fused proteins combined with liposomes and Toll-like Receptor specific adjuvants, are in advanced stages of clinical development.
The recombinant viral vector vaccines use a replicating or non-replicating (abortive) viral vector as a carrier for antigens of a pathogen and production of the antigens is induced in cells infected with the viral vector. They aim to induce a specific adaptive response against the pathogen specific antigen structures, while also providing some innate immune stimulation. An example are the recently licensed adenovirus vector-based COVID-19 vaccines. For TB, several candidate vaccines based on viral vectors, including Modified Vaccinia Ankara (MVA) and adenoviruses, are in early stages of clinical development.
The DNA/RNA vaccines contain the genetic information of a pathogen specific antigen which is then produced by target cells inoculated with the DNA or mRNA. Progress has been made in the delivery of DNA (electroporation) and of mRNA formulated into lipid nanoparticles (LNP). Examples are the licensed mRNA vaccines for COVID-19. For TB, nucleic acid-based candidate vaccines have yet to enter clinical development stages.