Ebola virus (EBOV) is a highly infectious filovirus causing a severe hemorrhagic fever in humans with fatality rates approaching 90%. We used the live attenuated recombinant vaccine vector vesicular stomatitis virus (VSV) to create a vaccine for EBOV. Ten cynomolgus macaques were immunized either intramuscularly (IM), orally (OR), or intranasally (IN) with VSVΔG/ZEBOVGP 28 days before receiving a lethal challenge of Zaire ebolavirus (ZEBOV). There were no signs of illness in the vaccinated animals, and no loss of lymphocytes typically seen during infection. ZEBOVGP-specific humoral and cell mediated immune responses (CMIR) were generated by all immunization routes. Surprisingly, in general, the IN route generated more potent humoral responses, while the IM route generated early IL-2 and IFN-γ CMIR. We demonstrate that a single dose of the VSVΔG/ZEBOVGP vaccine delivered by any of the three routes induces cellular and humoral immune responses and protects non-human primates against a lethal challenge of ZEBOV.
The 2013–2016 Ebola virus disease (EVD) was the first time that the spread of the virus reached epidemic status. There are no licensed vaccines; however the most advanced candidate rVSV-ZEBOV vaccine, is a live-attenuated vesicular stomatitis virus encoding the Ebola virus glycoprotein (GP), and has demonstrated efficacy in a ring-vaccination trial. However, several EVD viral vector vaccine trials have reported adverse events that could limit administration to certain populations. The establishment of robust anamnestic responses has yet to be fully understood with these candidates and may be limited by potential anti-vector immunity. We designed EVD DNA vaccines as an alternative platform with a remarkable safety profile that is serology independent, allowing for possible repeat vector administration. We designed 3 novel synthetic Zaire Ebola virus (EBOV) GP DNA sequences which were tested alone or as multivalent formulations delivered by in vivo intramuscular (IM) or intradermal (ID) electroporation (EP). The EBOV-GP DNA vaccines were highly protective against lethal EBOV-Makona challenge in cynomolgus macaques, with 100% protection in NHPs receiving vaccine by ID-EP delivery and 75% protection in NHPs receiving 2 doses IM-EP. Vaccinated NHPs had no detectable viremia following challenge. Animals (n=4–5/group) injected with different IM-EP or ID-EP DNA regimens were followed to monitor long-term immunogenicity. NHPs have durable total IgG antibody titers and T cells responses to EBOV GP antigen, including polyfunctional CD4 and CD8 T cells and responses in memory subset populations. Together, the data strong support EBOV-GP DNA vaccine delivery for protection and the generation of robust memory immune responses.
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