Can vaccines control bacterial virulence and pathogenicity? : the advantage of fitness over virulence.

Some vaccines, such as diphtheria toxoid and acellular pertussis vaccines (aPVs), may favor the emergence of less pathogenic strains of the respective bacteria they target. This review discusses the impact of the wide use of aPV on phenotype evolutions and their beneficial consequences in the light of the diphtheria toxoid immunization program experience and structuring evidence review in a causal analysis following Bradford Hill's causality criteria. All aPVs contain the pertussis toxin (PT), the main virulence factor of , alone or with one adhesin (filamentous hemagglutinin (FHA)), two adhesins (FHA and pertactin (PRN)) or four adhesins (FHA, PRN and two fimbriae (Fim 2/3)). In countries where the coverage of aPVs containing PRN is high, PRN negative isolates are increasing in prevalence, but isolates nonproducing the other antigens are rarely reported. We hypothesize that the selective pressure at play with PRN should exist against all aVP antigens, although detection biases may hinder its detection for other antigens, especially PT. PT being responsible for clinically frank cases of the disease, the opportunity to collect PT negative isolates is far lower than to collect PRN negative isolates which have a limited clinical impact. The replacement of the current by far less pathogenic isolates no longer producing the factors contained in aPVs should be expected as a consequence of the wide aPV use.