We previously described the generation of a novel Ebola virus (EBOV) vaccine based on inactivated rabies virus (RABV) containing EBOV glycoprotein (GP) incorporated in the RABV virion. Our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (NHPs). Protection against viral challenge depended largely on the quality of the humoral immune response against EBOV GP.Here we present the extension and improvement of this vaccine by increasing the amount of GP incorporation into virions via GP codon-optimization as well as the addition of Sudan virus (SUDV) and Marburg virus (MARV) GP containing virions. Immunogenicity studies in mice indicate similar immune responses for both SUDV GP and MARV GP compared to EBOV GP. Immunizing mice with multiple antigens resulted in immune responses similar to immunization with a single antigen. Moreover, immunization of NHP with the new inactivated RABV EBOV vaccine resulted in high titer neutralizing antibody levels and 100% protection against lethal EBOV challenge when applied with adjuvant.Our results indicate that an inactivated polyvalent vaccine against RABV filoviruses is achievable. Finally, the novel vaccines are produced on approved VERO cells and a clinical grade RABV/EBOV vaccine for human trials has been produced.
SAD B19 is an attenuated vaccine virus for oral vaccination of carnivores against rabies. The safety of SAD B19 was investigated in 16 animal species by different routes of administration. During the observation period all animals given the vaccine virus, irrespective of the route of administration, did not show any clinical signs of rabies, with the exception of certain rodent species. In these animals a low residual pathogenicity was observed, however transmission of the vaccine virus to control animals was not demonstrable. No vaccine virus could be detected in the saliva of the six mammal species examined. Furthermore, the genetical stability was shown for SAD B19 through passaging in neural tissue of dogs, foxes and mice. From the results presented here on innocuity and stability, it can be concluded that SAD B19 rabies vaccine is suitable for oral vaccination campaigns for carnivores against rabies.
The immunogenic properties of an E1-deleted, human adenovirus type 5 (Ad5) vaccine virus with activity against rabies were examined in mice, foxes and dogs using different routes of administration. NMRI mice received 10 5n8 , 10 5n3 , 10
Safety of the modified live rabies virus vaccine, SAD B19, was studied in striped skunks (Mephitis mephitis). Seven skunks received 10(7.9) foci formatting units by direct oral administration. In four cages, a vaccinated animal was placed with a control animal, the other three vaccinated skunks were housed individually. Saliva and nasal swabs were collected 1, 2, 4, 24, 48, and 72 hr post-vaccination. From all vaccinated and control animals (n = 11) blood samples were collected 0, 28, 56, 84, and 296 days post-vaccination. Three of seven vaccinated skunks seroconverted. None of the control animals had detectable levels of rabies virus neutralizing antibodies. Also no vaccine virus was isolated from the nasal and saliva swabs collected from any animal. Thus, SAD B19 was innocuous for skunks in our study after direct oral administration at field concentration.
A comparative study of immunogenicity and efficacy of the oral rabies virus vaccine SAD P5/88 in raccoon dogs and foxes was conducted. The raccoon dogs received 10(6.9) (n = 6), 10(6.3) (n = 6) or 10(5.7) FFU SAD P5/88 (n = 5) by direct oral application, and subsequently all animals seroconverted. The foxes received 10(7.2) (n = 4), 10(6.2) (n = 4), 10(5.2) (n = 4) and 10(4.2) FFU SAD P5/88 (n = 5) by the same route. On days 106 and 196 post vaccination 10 raccoon dogs and 16 foxes were challenged with a relevant street virus, respectively. All 10 raccoon dogs vaccinated with 10(6.3) (n = 5) or 10(5.7) FFU SAD P5/88 (n = 5) survived the challenge, whereas all control animals (n = 5) died of rabies. Two foxes vaccinated with 10(4.2) FFU and one fox vaccinated with 10(5.2) FFU died of rabies on day 7, 17 and 12 post infection, respectively. Also all control foxes succumbed to rabies. Our findings demonstrate that SAD P5/88 is not only an effective vaccine for oral vaccination of foxes but also for that of raccoon dogs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.