A Novel Rabies Vaccine Based on a Recombinant Bovine Herpes Virus Type 1 Expressing Rabies Virus Glycoprotein

Zhao, Caiquan; Gao, Jie; Wang, Yongzhi; Ji, Lina; Qian, Hui; Hu, Wei; Yang, Yang

doi:10.3389/fmicb.2022.931043

“…This suggests a higher immunogenicity of RABV G as compared to vector proteins. Similar observations were made in studies using rabies recombinant vaccines based on bovine herpesvirus (BHV, [50]) and canine distemper virus (CDV [51]).…”

Section: Discussionsupporting

confidence: 73%

Immune response after oral immunization of goats and foxes with an NDV vectored rabies vaccine candidate

Murr,

Freuling,

Pérez-Bravo

et al. 2024

PLoS Negl Trop Dis

1

0

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Vaccination of the reservoir species is a key component in the global fight against rabies. For wildlife reservoir species and hard to reach spillover species (e. g. ruminant farm animals), oral vaccination is the only solution. In search for a novel potent and safe oral rabies vaccine, we generated a recombinant vector virus based on lentogenic Newcastle disease virus (NDV) strain Clone 30 that expresses the glycoprotein G of rabies virus (RABV) vaccine strain SAD L16 (rNDV_GRABV). Transgene expression and virus replication was verified in avian and mammalian cells. To test immunogenicity and viral shedding, in a proof-of-concept study six goats and foxes, representing herbivore and carnivore species susceptible to rabies, each received a single dose of rNDV_GRABV (108.5 TCID50/animal) by direct oral application. For comparison, three animals received the similar dose of the empty viral vector (rNDV). All animals remained clinically inconspicuous during the trial. Viral RNA could be isolated from oral and nasal swabs until four (goats) or seven days (foxes) post vaccination, while infectious NDV could not be re-isolated. After four weeks, three out of six rNDV_GRABV vaccinated foxes developed RABV binding and virus neutralizing antibodies. Five out of six rNDV_GRABV vaccinated goats displayed RABV G specific antibodies either detected by ELISA or RFFIT. Additionally, NDV and RABV specific T cell activity was demonstrated in some of the vaccinated animals by detecting antigen specific interferon γ secretion in lymphocytes isolated from pharyngeal lymph nodes. In conclusion, the NDV vectored rabies vaccine rNDV_GRABV was safe and immunogenic after a single oral application in goats and foxes, and highlight the potential of NDV as vector for oral vaccines in mammals.

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“…This suggests a higher immunogenicity of RABV G as compared to vector proteins. Similar observations were made in studies using rabies recombinant vaccines based on bovine herpesvirus (BHV, (44)) and canine distemper virus (CDV (45)).…”

Section: Discussionsupporting

confidence: 71%

Oral immunization of goats and foxes with a recombinant NDV vectored rabies vaccine

Murr,

Freuling,

Pérez-Bravo

et al. 2023

Preprint

0

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Vaccination of the reservoir species is a key component in the global fight against rabies. For wildlife reservoir species and hard to reach spillover species (e. g. ruminant farm animals), oral vaccination is the only solution. In search for a novel potent and safe oral rabies vaccine, we generated a recombinant vector virus based on lentogenic Newcastle disease virus (NDV) strain Clone 30 that expresses the glycoprotein G of rabies virus (RABV) vaccine strain SAD L16 (rNDV_GRABV). Transgene expression and virus replication was verified in avian and mammalian cells. To test immunogenicity and viral shedding, in a proof-of-concept study six goats and foxes, representing herbivore and carnivore species susceptible to rabies, each received a single dose of rNDV_GRABV (108.5 TCID50/animal) by direct oral application. For comparison, three animals received the similar dose of the empty viral vector (rNDV). All animals remained clinically inconspicuous during the trial. Viral RNA could be isolated from oral and nasal swabs until four (goats) or seven days (foxes) post vaccination, while infectious NDV could not be re-isolated. After four weeks, three out of six rNDV_GRABV vaccinated foxes developed RABV binding and virus neutralizing antibodies. Five out of six rNDV_GRABV vaccinated goats displayed RABV G specific antibodies either detected by ELISA or RFFIT. Additionally, NDV and RABV specific T cell activity was demonstrated in some of the vaccinated animals by detecting antigen specific interferon γ secretion in lymphocytes isolated from pharyngeal lymph nodes. In conclusion, the NDV vectored rabies vaccine rNDV_GRABV was safe and immunogenic after a single oral application in goats and foxes, and highlight the potential of NDV as vector for oral vaccines  in mammals.

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“…The protective immune responses generated by theCanine adenovirus 2 rabies virus glycoprotein (CAV2-RVG) through intramuscular, intranasal, and oral immunization in mice and dogs were quite appreciable [107,108]. Furthermore, other viral vectors, including Parapoxvirus Orf virus (ORFV) [109], vesicular stomatitis virus (VSV) [110,111], raccoon poxvirus (RCN) [112], single-cycle flavivirus [113], Newcastle disease virus (NDV) [114], and bovine herpes virus type I (BHV-1) [115] expressing rabies virus glycoprotein, effectively induce RVNAs and remain as potent vaccine candidates. Still, a common obstacle with the viral vectors is the host's preexisting immunity to certain vectors that could minimize the efficacy of the vaccine.…”

Section: Parenteral Viral Vector Rabies Vaccinesmentioning

confidence: 99%

Developments in Rabies Vaccines: The Path Traversed from Pasteur to the Modern Era of Immunization

Natesan

¹

,

Isloor

²

,

Balamurugan

³

et al. 2023

Vaccines

13

0

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Rabies is a disease of antiquity and has a history spanning millennia ever since the first interactions between humans and dogs. The alarming fatalities caused by this disease have triggered rabies prevention strategies since the first century BC. There have been numerous attempts over the past 100 years to develop rabies vaccineswith the goal of preventing rabies in both humans and animals. Thepre-Pasteurian vaccinologists, paved the way for the actual history of rabies vaccines with the development of first generation vaccines. Further improvements for less reactive and more immunogenic vaccines have led to the expansion of embryo vaccines, tissue culture vaccines, cell culture vaccines, modified live vaccines, inactivated vaccines, and adjuvanted vaccines. The adventof recombinant technology and reverse genetics have given insight into the rabies viral genome and facilitated genome manipulations, which in turn led to the emergence of next-generation rabies vaccines, such as recombinant vaccines, viral vector vaccines, genetically modified vaccines, and nucleic acid vaccines. These vaccines were very helpful in overcoming the drawbacks of conventional rabies vaccines with increased immunogenicity and clinical efficacies. The path traversed in the development of rabies vaccines from Pasteur to the modern era vaccines, though, faced numerous challenges;these pioneering works have formed the cornerstone for the generation of thecurrent successful vaccines to prevent rabies. In the future, advancements in the scientific technologies and research focus will definitely lay the path for much more sophisticated vaccine candidates for rabies elimination.

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A Novel Rabies Vaccine Based on a Recombinant Bovine Herpes Virus Type 1 Expressing Rabies Virus Glycoprotein

Cited by 5 publications

References 38 publications

Immune response after oral immunization of goats and foxes with an NDV vectored rabies vaccine candidate

Immune response after oral immunization of goats and foxes with an NDV vectored rabies vaccine candidate

Oral immunization of goats and foxes with a recombinant NDV vectored rabies vaccine

Developments in Rabies Vaccines: The Path Traversed from Pasteur to the Modern Era of Immunization

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