MOLECULAR EVOLUTION OF IMMUNODEFICIENCY-ASSOCIATED VDPV TYPE 2 CASE FROM ARGENTINA

LEMA C; TORRES C (AUTORA PARA CORRESPONDENCIA); PASINOVICH M; BULLARD K; SCHMIDT A; CASTRO C; BURNS C; FREIRE MC; JORBA J

Congreso; EUROPIC 2022; 2022

We studied the genomic evolution of eleven type 2 immunodeficient vaccine-derived poliovirus (iVDPV2) isolates obtained over a 352-day period from a non-paralytic patient from Argentina with X-Linked agammaglobulinemia. The patient received two doses of trivalent oral poliovirus vaccine (tOPV) in November 2015 and February 2016. iVDPV excretion apparently ceased after the first day of treatment with the antiviral pocapavir. The iVDPV isolates were characterized by limited divergence from parental Sabin 2 strain with a range of estimated nucleotide similarity between 99.49% and 99.59% of total open reading frame positions. The two key determinants for the attenuation of Sabin 2 were reverted and represented early evolutionary events. Seven amino acid changes were detected in the capsid region; none mapped to known neutralizing antigenic sites or to the VP1 hypervariable region. Inferred phylogenetic trees yielded similar topologies among distinct genomic regions and were consistent with the detection of a single evolutionary lineage from parental Sabin 2 strain and with stepwise accumulation of substitutions compatible with sampling time. Results from molecular phylogenies inferred under distinct clock models and using different genomic regions yielded date estimates of OPV2 origin compatible with establishment of infection from the first dose of tOPV. The date of the common ancestral node to all iVDPV2s was estimated to be about 4 days before detection of the first VDPV2. Understanding intra-patient evolution of a prolonged iVDPV excretor is important in the context of endgame strategies to achieve the goal of polio eradication.