Dual Injection Ebola Virus Glycoprotein Synthetic DNA Vaccines Are Protective

A simple intradermalanti-Ebola DNA vaccine may generate strong immunogenicity and induce long-term immune responses in nonhuman primates.

A simple intradermally administered anti-Ebola DNA vaccine may generate strong immunogenicity and induce long-term immune response in nonhuman primates, according to a study recently published in the Journal of Infectious Diseases.

Although there have been significant breakthroughs in the Ebola virus disease vaccine development field, there remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses. In addition, there is a need for a preventive vaccine that is deliverable to highly vulnerable populations that include children, immune-compromised individuals, and pregnant women. A synthetic DNA vaccine may be a reasonable candidate because it is non-live, nonviral, and able to drive humoral and T-cell immunity along with establishing a long-term immunologic memory. Therefore, this study designed a novel synthetic anti-Ebola virus glycoprotein DNA vaccine as a strategy to expand protective breadth against diverse Ebola virus strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal Ebola virus-Makona challenge in nonhuman primates.

The anti-Ebola virus glycoprotein DNA vaccination was delivered in a multiple-injection regimen by intramuscular administration and in a 2-injection regimen by intradermal administration, followed by electroporation. Intradermal-electroporation delivery is an alternate route for vaccine administration that is immunogenic and potentially dose sparing, which are potential advantages for vaccine delivery in an outbreak setting and for more sensitive populations. Long-term immunogenicity was monitored in nonhuman primates for >1 year before they received a final boost immunization to evaluate long-term memory recall responses. Nonhuman primates were challenged on day 20 postimmunization with 1000 50% tissue culture infective dose of Ebola virus/H.sapiens-tc/GIN/2014/Makona-C07. Oral, nasal, and rectal swabs were collected from nonhuman primates and virus was quantitated.

Results showed that multiple-injection regimens of the anti-Ebola virus glycoprotein DNA vaccine delivered by intramuscular administration followed by electroporation were 100% protective against the lethal Ebola virus-Makona challenge. Of note, when the anti-Ebola virus glycoprotein DNA vaccine was by 2 injections delivered intradermally followed by electroporation, a strong immunogenicity was generated and was also 100% protective against the lethal Ebola virus-Makona challenge. Further, although reports of long-term immunogenicity following DNA or other experimental vaccine administration are lacking, results showed that the anti-Ebola virus glycoprotein DNA vaccine induced long-term immune responses in the nonhuman primates. The response was detectable for at least 1 year after final vaccination and generated a strong recall response after final boost. After immunization, there was a robust induction of glycoprotein-specific antibody responses and the establishment of cytokine-producing, antigen-specific memory T-cell responses.

Overall, the study authors concluded that, “DNA vaccines can be delivered way in advance, as preexposure prophylaxis to those living in at-risk regions, first responders, military personnel, and travelers [and t]his vaccine could be studied as a simple serology-independent boost for previously vaccinated persons, including those who have received recombinant vesicular stomatitis virus — anti-Zaire ebolavirus or recombinant viral vectors, to prevent loss of seropositivity to anti-Ebola virus glycoprotein, and possibly extend a longer window of immunity.”

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Patel A, Reuschel EL, Kraynyak KA, et al. Protective efficacy and long-term immunogenicity in cynomolgus macaques by Ebola virus glycoprotein synthetic DNA vaccines [published online October 10, 2018] J Infect Dis. doi: 10.1093/infdis/jiy537