ABSTRACT
Successful bacterial vaccines are composed of either killed or attenuated whole bacteria, detoxified exotoxins, or polysaccharides (and polysaccharide-protein conjugates). A newer vaccine development approach uses bacterial surface proteins as purified subunits, albeit in combination with a detoxified exotoxin. Acellular pertussis vaccines, the first example of this strategy of exploiting surface protein subunits, may contain, in addition to pertussis toxin (PT), the Bordetella pertussis pertactin (PRN), filamentous hemagglutinin (FHA), and fimbriae (FIM). Other nonencapsulated pathogenic bacteria such as nontypable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (M. cat) are potential targets for using surface components other than capsular polysaccharides as vaccine components. However, in terms of immune evasion, there is a major difference between B. pertussis and NTHi/M. cat. Bordetella exhibits rather limited antigenic variability in its various surface components and exotoxins such as PRN, FHA, FIM and pertussis toxin (PT), and adenylate cyclase (AC). B. pertussis may evade host immune responses by the immunomodulating effects of PT and AC. Both NTHi and M. cat use the antigenic variability of surface and secreted components to evade the human immune response. This hampers the identification of candidate antigens and complicates vaccine development. Although oral immunization with killed NTHi of adults with a history of chronic recurrences of respiratory NTHi infectious diseases has shown an impact on NTHi carriage and subsequent diseases [1-3], the duration of this effect is not known. However, these findings have demonstrated the
feasibility of immunization for protecting against NTHi infection. With respect to the potential of immune escape, it can be postulated that a multicomponent vaccine targeting a few components associated with essential biological functions would be needed for successful immunization. Such a multicomponent product can be either killed or live attenuated bacteria, or a multicomponent subunit. In the case of whole bacteria, it would be beneficial to genetically delete highly variable and nonprotective antigens and to up-regulate (minor) conserved, biologically essential, and protective components. Another option could be the use of outer membrane vesicles extracted from such manipulated bacteria.
