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Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb.

Qiu X, Audet J, Wong G, Fernando L, Bello A, Pillet S, Alimonti JB, Kobinger GP - Sci Rep (2013)

Bottom Line: Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans.The survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune responses.The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks.

View Article: PubMed Central - PubMed

Affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.

ABSTRACT
Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV-infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune responses. In order to evaluate whether the immune response induced in NHPs during the ZMAb treatment and EBOV challenge is sufficient to protect survivors against a subsequent exposure, animals that survived the initial challenge were rechallenged at 10 or 13 weeks after the initial challenge. The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks. The data indicate that a robust immune response was generated during the successful treatment of EBOV-infected NHPs with EBOV, which resulted in sustained protection against a second lethal exposure.

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Related in: MedlinePlus

Clinical parameters.Changes in various clinical parameters over the course of the second experiment, Group A is the rechallenged group while group B is the naïve control group. (A) Daily clinical score for each individual animal; (B) temperature; (C) white blood cell count (WBC); (D) platelet count (PLT); (E) alkaline phosphatase levels (ALP); (F) alanine aminotransferase levels (ALT); (G) amylase levels (AMY); and (H) % change in weight.
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f3: Clinical parameters.Changes in various clinical parameters over the course of the second experiment, Group A is the rechallenged group while group B is the naïve control group. (A) Daily clinical score for each individual animal; (B) temperature; (C) white blood cell count (WBC); (D) platelet count (PLT); (E) alkaline phosphatase levels (ALP); (F) alanine aminotransferase levels (ALT); (G) amylase levels (AMY); and (H) % change in weight.

Mentions: In a subsequent experiment24, 8 cynomolgus macaques were challenged with EBOV and treated using Ad-IFN and ZMAb starting at 48 or 72 hours post-infection, followed by two administrations of ZMAb 72 hours apart and were monitored for 28 days. Six animals survived, one animal in each treatment group died along with two control animals, one receiving a PBS treatment and one receiving normal mouse IgG. The survivors were rechallenged 13 weeks after the initial infection along with two naïve cynomolgus macaque controls (Figure 2A). Four of the 6 animals survived the rechallenge (Figure 2B; p = 0.0039) with low to undetectable viremia (Figure 2C, Supplementary Table 1). The surviving animals experienced no clinical signs of disease (Figure 3A, summarised in Table 1) or fever (Figure 3B). Platelet and white blood cell counts were stable throughout the experiment (Figures 3C and 3D, respectively) and there were no changes in liver enzyme activity (Figures 3E and 3F) or levels of amylase (Figure 3G). In contrast, both controls and animal A6 exhibited decreased platelet counts, white blood cell counts (for B2 and A6), and amylase activity as well as increased liver enzyme activity. Animal A5 was found dead on day 7, therefore blood chemistry and a complete blood count could not be evaluated. All the survivors gained weight throughout the experiment while the animals that succumbed to the infection experienced weight loss (Figure 3H).


Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb.

Qiu X, Audet J, Wong G, Fernando L, Bello A, Pillet S, Alimonti JB, Kobinger GP - Sci Rep (2013)

Clinical parameters.Changes in various clinical parameters over the course of the second experiment, Group A is the rechallenged group while group B is the naïve control group. (A) Daily clinical score for each individual animal; (B) temperature; (C) white blood cell count (WBC); (D) platelet count (PLT); (E) alkaline phosphatase levels (ALP); (F) alanine aminotransferase levels (ALT); (G) amylase levels (AMY); and (H) % change in weight.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842534&req=5

f3: Clinical parameters.Changes in various clinical parameters over the course of the second experiment, Group A is the rechallenged group while group B is the naïve control group. (A) Daily clinical score for each individual animal; (B) temperature; (C) white blood cell count (WBC); (D) platelet count (PLT); (E) alkaline phosphatase levels (ALP); (F) alanine aminotransferase levels (ALT); (G) amylase levels (AMY); and (H) % change in weight.
Mentions: In a subsequent experiment24, 8 cynomolgus macaques were challenged with EBOV and treated using Ad-IFN and ZMAb starting at 48 or 72 hours post-infection, followed by two administrations of ZMAb 72 hours apart and were monitored for 28 days. Six animals survived, one animal in each treatment group died along with two control animals, one receiving a PBS treatment and one receiving normal mouse IgG. The survivors were rechallenged 13 weeks after the initial infection along with two naïve cynomolgus macaque controls (Figure 2A). Four of the 6 animals survived the rechallenge (Figure 2B; p = 0.0039) with low to undetectable viremia (Figure 2C, Supplementary Table 1). The surviving animals experienced no clinical signs of disease (Figure 3A, summarised in Table 1) or fever (Figure 3B). Platelet and white blood cell counts were stable throughout the experiment (Figures 3C and 3D, respectively) and there were no changes in liver enzyme activity (Figures 3E and 3F) or levels of amylase (Figure 3G). In contrast, both controls and animal A6 exhibited decreased platelet counts, white blood cell counts (for B2 and A6), and amylase activity as well as increased liver enzyme activity. Animal A5 was found dead on day 7, therefore blood chemistry and a complete blood count could not be evaluated. All the survivors gained weight throughout the experiment while the animals that succumbed to the infection experienced weight loss (Figure 3H).

Bottom Line: Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans.The survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune responses.The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks.

View Article: PubMed Central - PubMed

Affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.

ABSTRACT
Ebola virus (EBOV) is one of the most lethal filoviruses, with mortality rates of up to 90% in humans. Previously, we demonstrated 100% and 50% survival of EBOV-infected cynomologus macaques with a combination of 3 EBOV-GP-specific monoclonal antibodies (ZMAb) administered at 24 or 48 hours post-exposure, respectively. The survivors demonstrated EBOV-GP-specific humoral and cell-mediated immune responses. In order to evaluate whether the immune response induced in NHPs during the ZMAb treatment and EBOV challenge is sufficient to protect survivors against a subsequent exposure, animals that survived the initial challenge were rechallenged at 10 or 13 weeks after the initial challenge. The animals rechallenged at 10 weeks all survived whereas 4 of 6 animals survived a rechallenge at 13 weeks. The data indicate that a robust immune response was generated during the successful treatment of EBOV-infected NHPs with EBOV, which resulted in sustained protection against a second lethal exposure.

Show MeSH
Related in: MedlinePlus