Abstract
Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested that, although sedation induced acute stress, experimental housing conditions did not induce traumatic levels of chronic stress. Acute behavioral and physiological responses to sedation were strongly correlated with immune responses to vaccination. These results suggest that oral vaccination holds great promise as a tool for the conservation of apes and other endangered tropical wildlife. They also imply that vaccine and drug trials on other captive species need to better account for the effects of stress on immune response.
Highlights
In 2014 the world was gripped by fears of an Ebola virus (EBOV) pandemic
Filorab1’s immunogenicity and lack of side-effects in captive chimpanzees bode well for its use to protect wild chimpanzees and gorillas endangered by EBOV
Filorab[1] produced immune responses comparable to those observed in the only previous EBOV vaccine trial on captive chimpanzees using a virus-like particle (VLP) vaccine[22] but did so with only one dose rather than the three doses given in the VLP study
Summary
In 2014 the world was gripped by fears of an Ebola virus (EBOV) pandemic. Few people realized that Ebola had already inflicted pandemic scale mortality on our closest relatives, killing about one third of the world’s gorillas and countless chimpanzees (Fig. 1)[1,2]. Our first step was to conduct trials on oral delivery of an EBOV vaccine to captive chimpanzees. We started with a captive trial because host evolutionary similarity is strongly correlated with disease susceptibility and vaccine effectiveness[7]: an effect implied in the fact that several early vaccines that were protective against Ebola challenge in mice were not protective in macaques[8]. We report results from a trial of the filorab[1] vaccine, which inserts the gene encoding the EBOV glycoprotein (GP) into the replication competent but highly attenuated SAD B19-based RABV vaccine[9].We vaccinated ten chimpanzees at the University of Louisiana Lafayette’s New Iberia Research Center with 1.5 × 108 focus forming units of vaccine, six orally and four intramuscularly (IM). To evaluate immunogenicity we performed enzyme-linked immunosorbant assays (ELISA) of antibodies specific to EBOV GP and RABV as well as assays of serum neutralizing activity against RABV and EBOV GP pseudo-typed vesicular stomatitis virus (VSV-EBOV)
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