Evaluation in nonhuman primates of vaccines against Ebola virus

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.

Figure

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.