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Evaluation in nonhuman primates of vaccines against Ebola virus.

Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB - Emerging Infect. Dis. (2002)

Bottom Line: No vaccines or treatments are available for human use.None of these strategies successfully protected nonhuman primates from robust challenge with EBOV.The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.

View Article: PubMed Central - PubMed

Affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. tom.geisbert@amedd.army.mil

ABSTRACT
Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV glycoprotein; liposomes containing lipid A and inactivated EBOV; and a concentrated, inactivated whole-virion preparation. None of these strategies successfully protected nonhuman primates from robust challenge with EBOV. The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.

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Sections of spleen from Ebola virus (EBOV)-infected animals. Top left, BALB/c mouse, note absence of polymerized fibrin (phosphotungstic acid [PTA] hematoxylin, original magnification X400). Field representative of five of five mice tested. Top right: guinea pig. Note discreet foci of polymerized fibrin (arrows) (PTA hematoxylin, original magnification X400). This field shows infrequent fibrin deposits; most fields in five of five animals examined showed no evidence of polymerized fibrin. Lower left: cynomolgus monkey. Note deposition of polymerized fibrin in red pulp (PTA hematoxylin, original magnification X400). Field representative of 25 of 25 monkeys. Lower right: cynomolgus monkey. Electron micrograph showing abundant fibrin deposits in red pulp (original magnification X5,300). Field representative of 11 of 11 monkeys examined.
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Figure 1: Sections of spleen from Ebola virus (EBOV)-infected animals. Top left, BALB/c mouse, note absence of polymerized fibrin (phosphotungstic acid [PTA] hematoxylin, original magnification X400). Field representative of five of five mice tested. Top right: guinea pig. Note discreet foci of polymerized fibrin (arrows) (PTA hematoxylin, original magnification X400). This field shows infrequent fibrin deposits; most fields in five of five animals examined showed no evidence of polymerized fibrin. Lower left: cynomolgus monkey. Note deposition of polymerized fibrin in red pulp (PTA hematoxylin, original magnification X400). Field representative of 25 of 25 monkeys. Lower right: cynomolgus monkey. Electron micrograph showing abundant fibrin deposits in red pulp (original magnification X5,300). Field representative of 11 of 11 monkeys examined.

Mentions: We also evaluated retrospectively EBOV-infected rodent tissues in parallel. Although sites of infection and morphologic changes between guinea pigs, mice, and nonhuman primates had many similarities, the lack of fibrin thrombi in spleen and visceral vasculature was particularly striking in the EBOV-infected mice (Figure). Fibrin deposition was seen in guinea pigs as reported (20), but fibrin deposits and thrombi were considerably less prevalent compared with deposits in nonhuman primates (Figure). Lymphocyte apoptosis was also less frequently observed by electron microscopy in rodent lymphatic tissues than in nonhuman primates. EBOV was demonstrated in liver, spleen, kidney, lung, adrenal gland, and lymph nodes of all necropsied monkeys by immunohistochemistry, electron microscopy, or virus infectivity titration.


Evaluation in nonhuman primates of vaccines against Ebola virus.

Geisbert TW, Pushko P, Anderson K, Smith J, Davis KJ, Jahrling PB - Emerging Infect. Dis. (2002)

Sections of spleen from Ebola virus (EBOV)-infected animals. Top left, BALB/c mouse, note absence of polymerized fibrin (phosphotungstic acid [PTA] hematoxylin, original magnification X400). Field representative of five of five mice tested. Top right: guinea pig. Note discreet foci of polymerized fibrin (arrows) (PTA hematoxylin, original magnification X400). This field shows infrequent fibrin deposits; most fields in five of five animals examined showed no evidence of polymerized fibrin. Lower left: cynomolgus monkey. Note deposition of polymerized fibrin in red pulp (PTA hematoxylin, original magnification X400). Field representative of 25 of 25 monkeys. Lower right: cynomolgus monkey. Electron micrograph showing abundant fibrin deposits in red pulp (original magnification X5,300). Field representative of 11 of 11 monkeys examined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369765&req=5

Figure 1: Sections of spleen from Ebola virus (EBOV)-infected animals. Top left, BALB/c mouse, note absence of polymerized fibrin (phosphotungstic acid [PTA] hematoxylin, original magnification X400). Field representative of five of five mice tested. Top right: guinea pig. Note discreet foci of polymerized fibrin (arrows) (PTA hematoxylin, original magnification X400). This field shows infrequent fibrin deposits; most fields in five of five animals examined showed no evidence of polymerized fibrin. Lower left: cynomolgus monkey. Note deposition of polymerized fibrin in red pulp (PTA hematoxylin, original magnification X400). Field representative of 25 of 25 monkeys. Lower right: cynomolgus monkey. Electron micrograph showing abundant fibrin deposits in red pulp (original magnification X5,300). Field representative of 11 of 11 monkeys examined.
Mentions: We also evaluated retrospectively EBOV-infected rodent tissues in parallel. Although sites of infection and morphologic changes between guinea pigs, mice, and nonhuman primates had many similarities, the lack of fibrin thrombi in spleen and visceral vasculature was particularly striking in the EBOV-infected mice (Figure). Fibrin deposition was seen in guinea pigs as reported (20), but fibrin deposits and thrombi were considerably less prevalent compared with deposits in nonhuman primates (Figure). Lymphocyte apoptosis was also less frequently observed by electron microscopy in rodent lymphatic tissues than in nonhuman primates. EBOV was demonstrated in liver, spleen, kidney, lung, adrenal gland, and lymph nodes of all necropsied monkeys by immunohistochemistry, electron microscopy, or virus infectivity titration.

Bottom Line: No vaccines or treatments are available for human use.None of these strategies successfully protected nonhuman primates from robust challenge with EBOV.The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.

View Article: PubMed Central - PubMed

Affiliation: U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. tom.geisbert@amedd.army.mil

ABSTRACT
Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV glycoprotein; liposomes containing lipid A and inactivated EBOV; and a concentrated, inactivated whole-virion preparation. None of these strategies successfully protected nonhuman primates from robust challenge with EBOV. The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.

Show MeSH
Related in: MedlinePlus