Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

Abstract

Significance In 2010, a large outbreak of poliomyelitis involving 445 laboratory-confirmed cases occurred in the Republic of Congo. The 47% case-fatality rate was unusually high. Outbreak severity was attributed to low immunization coverage but vaccine-mediated immunity against the outbreak virus was never investigated. We isolated the poliovirus type 1 responsible for the outbreak and located its evolutionary origins to Southeast Asia. Fatal cases showed evidence for previous vaccination against polioviruses and the outbreak virus was refractive against neutralization by monoclonal and vaccine-derived antibodies. This pointed to immune escape contributing to the severity of the outbreak. Sustained vaccination regimens in polio-free regions, together with clinical and environmental poliovirus surveillance will be necessary to combat antigenetically variant polioviruses in the poliomyelitis eradication endgame.

Why does drug resistance readily evolve but vaccine resistance does not?

“…[10,20–23]), although the public health consequences of these evolutionary trajectories have often been unclear (e.g. [10,22,24–26]).…”

Characterization of Poliovirus Neutralization Escape Mutants of Single-Domain Antibody Fragments (VHHs)

“…The VP1 V47L and VP4 I62T substitutions even occur as single-amino-acid substitutions; thus, they are fully responsible for the resistant phenotype of variants 8A_1 and 21E_5, respectively. Mutants resistant to conventional antibodies tend to mutate in epitopes that are more exposed on the surface of the capsid, e.g., in the loop regions at the 5-fold axis of symmetry (BC and EF loops of VP1) or the loops surrounding the canyon (EF loop of VP2 and GH loop of VP1) (27)(28)(29)(30)(31)(32)(33)(34)(35). The dimensions of conventional antibodies (approximately 10 times those of VHHs) usually allow them to recognize only these epitopes on the capsid that are easily accessible; therefore, escape mutations are clustered in defined regions that are consistent with the area of the antigen binding site at the tip of each Fab.…”

Molecular epidemiology and phylogenetics of human enteroviruses: Is there a forest behind the trees?

“…The seroprevalence may, or may, not increase after an outbreak . At the individual level, the presence of antibodies of a specific type may not be sufficient to prevent the disease . The expansion and extinction of enterovirus genetic variants occur within the same type and are therefore more likely to be driven by intrinsic population dynamic patterns than by herd immunity.…”

“…42,85 At the individual level, the presence of antibodies of a specific type may not be sufficient to prevent the disease. 86 The expansion and extinction of enterovirus genetic variants occur within the same type 32 and are therefore more likely to be driven by intrinsic population dynamic patterns than by herd immunity. The main factor driving such "intrinsic" expansion/ extinction can be seasonality of infection.…”