Figure 1
Figure 1. Experimental design and sequence of plasma infusions and follow-up of chimpanzees. Experiment I assessed the infectivity of plasma that tested HCV RNA negative by licensed diagnostic assays and was obtained in the days just before ramp-up viremia. (A) Fifty milliliters of pre–ramp-up phase plasma from each of 5 commercial apheresis donors was infused sequentially during a single experimental procedure into chimp X355. (B) When transmission was linked to 1 donor by phylogenetic sequencing, 50-mL plasma samples from each of 4 earlier donations from that implicated donor were transfused to a second animal (X331) at 9-week intervals. Both animals were followed for virologic, serologic, and cell-mediated immune responses to assess evidence of HCV infection. Experiment II examined the infectivity of samples from 5 donors who had intermittent low-level HCV RNA (“blips”) detected during the eclipse phase of HCV infection by infusions into chimp X331. (C) Phase 1: Infusion of a pool of 250 mL (50 mL of plasma/donor from donations collected subsequent to blips) of HCV RNA-negative plasma from the eclipse phase. (D) Phase 2: 50-mL plasma samples from blip viremic units from the eclipse phase from the same 5 donors were sequentially infused at 6-week intervals. Phase 1 and phase 2 infusions did not transmit HCV infection to the recipient animal (chimp X331). (E) Phase 3: To confirm this chimp's susceptibility to HCV infection, 50-mL plasma samples from each of 3 progressively higher titer HCV RNA-positive donations collected during the early ramp-up phase of infection from one of these 5 donors were infused at 8-week intervals. In experiment III, chimp X355 who had spontaneously recovered from HCV infection and lost anti-HCV as well as virus, was rechallenged 3 years later to determine whether prior infection conferred protection against reinfection. (F1) Infusion of 50 mL of plasma containing an estimated 80 HCV RNA copies (1.6 copies/mL) from the previous infecting donation. (F2) Rechallenge with 50 mL of plasma containing an estimated 300 000 HCV RNA copies (6000 copies/mL) from a subsequent early ramp-up–phase donation from the same donor.

Experimental design and sequence of plasma infusions and follow-up of chimpanzees. Experiment I assessed the infectivity of plasma that tested HCV RNA negative by licensed diagnostic assays and was obtained in the days just before ramp-up viremia. (A) Fifty milliliters of pre–ramp-up phase plasma from each of 5 commercial apheresis donors was infused sequentially during a single experimental procedure into chimp X355. (B) When transmission was linked to 1 donor by phylogenetic sequencing, 50-mL plasma samples from each of 4 earlier donations from that implicated donor were transfused to a second animal (X331) at 9-week intervals. Both animals were followed for virologic, serologic, and cell-mediated immune responses to assess evidence of HCV infection. Experiment II examined the infectivity of samples from 5 donors who had intermittent low-level HCV RNA (“blips”) detected during the eclipse phase of HCV infection by infusions into chimp X331. (C) Phase 1: Infusion of a pool of 250 mL (50 mL of plasma/donor from donations collected subsequent to blips) of HCV RNA-negative plasma from the eclipse phase. (D) Phase 2: 50-mL plasma samples from blip viremic units from the eclipse phase from the same 5 donors were sequentially infused at 6-week intervals. Phase 1 and phase 2 infusions did not transmit HCV infection to the recipient animal (chimp X331). (E) Phase 3: To confirm this chimp's susceptibility to HCV infection, 50-mL plasma samples from each of 3 progressively higher titer HCV RNA-positive donations collected during the early ramp-up phase of infection from one of these 5 donors were infused at 8-week intervals. In experiment III, chimp X355 who had spontaneously recovered from HCV infection and lost anti-HCV as well as virus, was rechallenged 3 years later to determine whether prior infection conferred protection against reinfection. (F1) Infusion of 50 mL of plasma containing an estimated 80 HCV RNA copies (1.6 copies/mL) from the previous infecting donation. (F2) Rechallenge with 50 mL of plasma containing an estimated 300 000 HCV RNA copies (6000 copies/mL) from a subsequent early ramp-up–phase donation from the same donor.

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