Asymptomatic immunodeficiency-associated vaccine-derived poliovirus infections in two UK children

Figures

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  Fig. 1. Schematic timeline of key events and microbial detections, from birth to the post-transplant period. Key clinical and microbiological events are shown for A Child 1 and B Child 2. IPV inactivated polio vaccine, OPV oral polio vaccine, IVIG intravenous immunoglobulin, VDPV vaccine-derived poliovirus.

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  Fig. 2. Correlation between intravenous immunoglobulin, haematopoetic stem cell transplant and shedding of infectious poliovirus. The relationship over time between Ig trough level (blue line), IVIg dose (red line), HSCT (black arrow), poliovirus isolation in stool (grey shading) and URT (grey and white hashed shading) is presented for A Child 1 and B Child 2. Source data are provided as a Source Data file. HSCT hematopoietic stem cell transplant, URT upper respiratory tract, Ig immunoglobulin.

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  Fig. 3. Estimation of the date of OPV exposure from sequence divergence. The figure represents the number of mutations from Sabin 1 and 3 vaccine strains (GenBank IDs AY184219 and AY184221). Data were adjusted to a linear function for the accumulation of nucleotide substitutions (Y = 0.2708*X − 11764, R2 = 93% for iVDPV1 and Y = 0.2328*X − 10032, R2 = 92% for iVDPV3). The date of initial Sabin 1 (A) and Sabin 3 (B) infection that led to the iVDPV1 and iVDPV3 cases was estimated by simple linear regression extrapolating the line for the evolution rate of nucleotide substitutions backward to 0 genome substitutions. Source data are provided as a Source Data file. OPV oral polio vaccine, iVDPV immunodeficiency-associated vaccine-derived poliovirus.

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  Fig. 4. Neurovirulence of iVDPV poliovirus strains in transgenic mice. A Transgenic mice expressing the poliovirus receptor (minimum n = 8 biologically independent mice per dilution) were inoculated intraspinally with stocks of representative iVDPV1, iVDPV3, Sabin 1 and Sabin 3 isolates, in duplicate. A, B The PD50 was calculated using the Spearman–Karber method. Data are presented as PD50 values ± 95% confidence intervals. Source data are provided as a Source Data file. CCID50 50% cell culture infectious dose, PD50 50% paralytic dose.