Population genomics of post-vaccine changes in pneumococcal epidemiology

Abstract

Whole genome sequencing of 616 asymptomatically carried pneumococci was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates revealed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant pre-vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the fall in pneumococcal disease rates after the vaccine’s introduction.

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

“…An example of vaccine induced selective pressure and natural selection occurring simultaneously was observed in the post PCV7 era. 18 Croucher et al., points out that a number of successful lineages that were vaccine-type prior to PCV7 introduction will likely persist through variants that have acquired non-vaccine type capsules through natural transformation from vaccine pressure, i.e., serotype switching. 18 As was the circumstance after the introduction of PCV7, it is probable that non-vaccine type capsular switch variants will persist and emerge from the PCV13 vaccine program.…”

“…18 Croucher et al., points out that a number of successful lineages that were vaccine-type prior to PCV7 introduction will likely persist through variants that have acquired non-vaccine type capsules through natural transformation from vaccine pressure, i.e., serotype switching. 18 As was the circumstance after the introduction of PCV7, it is probable that non-vaccine type capsular switch variants will persist and emerge from the PCV13 vaccine program. Fortunately, the extent of serotype replacement and serotype switching on IPD and pneumonia rates has been minimal to this point.…”

“…24 There was a notable rise in strains 19A and 7F. 18 The proportion of IPD caused by 19A increased from 0% in 1991–1994 to 18% in 2001–2003. 30 Additionally, strains 3, 15, 22F and 33F increased in children under the age of five, however, these strains were also seen among adults.…”

“…This vaccine contained the CPS of seven highly virulent serotypes of S. pneumoniae covalently conjugated to the carrier protein, non-toxic diphtheria toxin mutant CRM197 (Table 1). 18 While this conjugate vaccine showed evidence of greater protection in children and herd effect among the population, 19 the effectiveness in adults was not well studied. 5 In 2010, a new conjugate vaccine was released in the United States, Prevnar® PCV13.…”

“…In 2006 it was reported that between 23–30% of children still carried pneumococci with no evidence of a decline in carriage prevalence. 18 , 23 Additionally, while PCV7 reduced the incidence of IPD by 97% for serotypes included in the vaccine in children under the age of five, infection from non-vaccine type serotypes increased by 22%. 5 This was also observed in the Netherlands, where IPD rates for non-vaccine serotypes increased by 13%.…”