Spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Abstract

Competitive interactions between pathogen strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures, however, this has rarely been measured due to inadequate data and analytical tools. Bordetella pertussis (B. pertussis), responsible for 160,000 deaths annually1, provides a rare natural experiment as many countries have switched from whole cell vaccines to acellular vaccines, which have very different immunogenic properties2,3. Here we use 3,344 sequences from 23 countries and build phylogenetic models to reveal that B. pertussis has substantial diversity within communities, with the relative fitness of local genotypes changing in response to switches in vaccine policy. We demonstrate that the number of transmission chains circulating within subnational regions is strongly associated with host population size. It takes 5-10 years for individual lineages to be homogeneously distributed throughout Europe or the United States. Increased fitness of pertactin-deficient strains following implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of national vaccine policies in shifting local diversity of a pathogen that still poses a large burden on global public health.

Evaluation of Whole-Cell and Acellular Pertussis Vaccines in the Context of Long-Term Herd Immunity

“…In agreement with this hypothesis, a genomic analysis of B. pertussis strains carried out in the United Kingdom showed that genes encoding for aP vaccine antigens have been found to evolve at a faster pace than genes encoding for other B. pertussis surface proteins [ 104 , 105 ]. Furthermore, a study was recently carried out on more than 3300 strains from 23 countries, which showed that, on average, there are more than 28 transmission chains circulating within a subnational region [ 106 ]. This study allowed us to detect that it took 5 to 10 years for B. pertussis to distribute homogeneously throughout Europe, with the same period of time required for the United States.…”

“…This study allowed us to detect that it took 5 to 10 years for B. pertussis to distribute homogeneously throughout Europe, with the same period of time required for the United States. The increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness may otherwise explain long-term genotype dynamics [ 106 ]. These findings highlight the role of vaccine policy in changing the local diversity of a pathogen that is responsible for 160,000 deaths a year.…”