The Early Evolution of Oral Poliovirus Vaccine Is Shaped by Strong Positive Selection and Tight Transmission Bottlenecks

Abstract

Summary The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

“…Specimen viral load is important when measuring intrahost diversity. We and others have shown that samples with low viral loads are prone to false positive iSNV and lower sensitivity [22,23,30]. A strength of our study is that we experimentally validated the accuracy of our variant calling by sequencing defined populations.…”

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

“…Specimen viral load is important when measuring intrahost diversity. We and others have shown that samples with low viral loads are prone to false positive iSNV and lower sensitivity 22 , 23 , 29 . A strength of our study is that we experimentally validated the accuracy of our variant calling by sequencing defined populations.…”

The Molecular Evolution of Type 2 Vaccine-Derived Polioviruses in Individuals with Primary Immunodeficiency Diseases

“…After the initial replication period of the OPV strains, the subsequent mutations would accumulate at a nearly uniform rate of 1 to 2% nucleotide changes per year [ 32 , 50 , 51 ]. Due to a strong positive selection in vaccinees immunized with type 2 OPV, the so-called gatekeeper mutations from the attenuated Sabin 2 strain, including three mutations at A481G, U2909C (VP1-I143T), and U398C, are rapidly selected and fixed in the first several weeks post-vaccination [ 35 , 52 , 53 ]. Those gatekeeper mutations may contribute to the virus replication fitness in the human intestine and higher initial evolution rates of iVDPV and cVDPV immediately after the OPV administration.…”

“…Historically, poliovirus quasi-species were analyzed by the conventional plaque cloning and Sanger sequencing of virus isolates. Recently, next-generation sequencing (NGS) technologies were applied to study viral quasi-species and the molecular evolution of various RNA viruses, including those of the OPV strains and cVDPVs, but not for those from iVDPV cases [ 25 , 52 , 53 ]. In the future, more comprehensive and quantitative analyses on the genetic diversity of the quasi-species of iVDPV variants in infected individuals, compared to those in cVDPV and OPV strains, using NGS will be required.…”

“…Recently, Valesano et al found that most OPV2-derived variants with the gatekeeper mutations that appeared in OPV recipients rapidly could not survive during virus transmission to the close contacts of the recipients due to the tight transmission bottleneck. This finding suggests distinct mechanisms of molecular evolution between viral replication in the hosts and during community transmission [ 52 ]. More detailed and comprehensive genetic characterization, taking the previously mentioned points on the molecular characteristics of iVDPV2 into account, is in progress to elucidate the relationship and molecular evolution of cVDPV2 and iVDPV2 in the Philippines.…”