The early evolution of oral poliovirus vaccine is shaped by strong positive selection and tight transmission bottlenecks

Abstract

The evolution of circulating vaccine-derived polioviruses (cVDPV) from components of the live-attenuated oral poliovirus vaccine (OPV) presents a major challenge to global polio eradication. This process has largely been characterized by consensus sequencing of isolates collected from routine surveillance, and little is known about the early evolution of OPV within vaccinated hosts. These early events are critical steps in the progression of OPV to cVDPV. Here, we use whole genome, high depth of coverage sequencing to define the evolutionary trajectories of monovalent type 2 OPV in a cluster-randomized trial of polio vaccines in Matlab, Bangladesh. By sequencing 416 longitudinal samples from 219 mOPV2 recipients and 81 samples from 52 household contacts, we were able to examine the extent of convergent evolution in vaccine recipients and track the amount of viral diversity transmitted to new hosts. Using time-series data from a synchronized point of vaccine administration, we identify strong positive selection of reversion mutations at three known attenuating sites within two months post-vaccination. Beyond these three recognized gate-keeper mutations, we identify 19 mutations that exhibit significant parallelism across vaccine recipients, providing evidence for early positive selection not previously detected by phylogenetic inference. An analysis of shared genetic variants in samples from vaccinated individuals and their household contacts suggests a tight effective bottleneck during transmission. The absence of positively selected variants among household contacts across the cohort suggests that this tight bottleneck limits the transmission of these early adaptive mutations. Together, our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of novel OPV2 and other next generation approaches.

Outbreaks of Circulating Vaccine-Derived Poliovirus in the World Health Organization Western Pacific Region, 2000–2021

“…those of the parental OPV strains (16)(17)(18)(19)(20). The VDPVs are defined as OPV-derived variants with more than 1% nucleotide divergence in the viral capsid protein VP1 from the Sabin 1 and Sabin 3 strains and more than 0.6% nucleotide divergence from the Sabin 2 strain (21).…”

“…For cVDPV definition see http://polioeradication.org/wpcontent/uploads/2016/09/Reporting-and-Classification-of-VDPVs_Aug2016_EN.pdf (20)…”