Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine

Verena Te Kamp; Virginia Friedrichs; Conrad M. Freuling; Ad Vos; Madlin Potratz; Antonia Klein; Luca M. Zaeck; Elisa Eggerbauer; Peter Schuster; Christian Kaiser; Steffen Ortmann; Antje Kretzschmar; Katharina Bobe; Michael R. Knittler; Anca Dorhoi; Stefan Finke; Thomas Müller

doi:10.3390/vaccines9010049

Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine

Verena Te Kamp, Virginia Friedrichs, Conrad M. Freuling, Ad Vos, Madlin Potratz, Antonia Klein, Luca M. Zaeck, Elisa Eggerbauer, Peter Schuster, Christian Kaiser, Steffen Ortmann, Antje Kretzschmar, Katharina Bobe, Michael R. Knittler, Anca Dorhoi, Stefan Finke, Thomas Müller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre-and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

Original language	English
Article number	49
Pages (from-to)	1-14
Number of pages	14
Journal	Vaccines
Volume	9
Issue number	1
DOIs	https://doi.org/10.3390/vaccines9010049
Publication status	Published - 14 Jan 2021
Externally published	Yes

Bibliographical note

Funding Information:
Funding: The project was funded in the frame of a research cooperation with IDT Biologika GmbH (now Ceva Santé Animale, France) into mechanisms of oral rabies vaccination. Parts of the project were supported by an intramural collaborative research grant at the Friedrich-Loeffler-Institut.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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Comparable Long-Term Rabies Immunity in Foxes after IntraMuscular and Oral Application Using a Third-Generation Oral Rabies Virus VaccineFinal published version, 821 KBLicence: CC BY

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Kamp, V. T., Friedrichs, V., Freuling, C. M., Vos, A., Potratz, M., Klein, A., Zaeck, L. M., Eggerbauer, E., Schuster, P., Kaiser, C., Ortmann, S., Kretzschmar, A., Bobe, K., Knittler, M. R., Dorhoi, A., Finke, S., & Müller, T. (2021). Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine. Vaccines, 9(1), 1-14. Article 49. https://doi.org/10.3390/vaccines9010049

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title = "Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine",

abstract = "The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre-and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.",

author = "Kamp, {Verena Te} and Virginia Friedrichs and Freuling, {Conrad M.} and Ad Vos and Madlin Potratz and Antonia Klein and Zaeck, {Luca M.} and Elisa Eggerbauer and Peter Schuster and Christian Kaiser and Steffen Ortmann and Antje Kretzschmar and Katharina Bobe and Knittler, {Michael R.} and Anca Dorhoi and Stefan Finke and Thomas M{\"u}ller",

note = "Funding Information: Funding: The project was funded in the frame of a research cooperation with IDT Biologika GmbH (now Ceva Sant{\'e} Animale, France) into mechanisms of oral rabies vaccination. Parts of the project were supported by an intramural collaborative research grant at the Friedrich-Loeffler-Institut. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jan,

day = "14",

doi = "10.3390/vaccines9010049",

language = "English",

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Kamp, VT, Friedrichs, V, Freuling, CM, Vos, A, Potratz, M, Klein, A, Zaeck, LM, Eggerbauer, E, Schuster, P, Kaiser, C, Ortmann, S, Kretzschmar, A, Bobe, K, Knittler, MR, Dorhoi, A, Finke, S & Müller, T 2021, 'Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine', Vaccines, vol. 9, no. 1, 49, pp. 1-14. https://doi.org/10.3390/vaccines9010049

TY - JOUR

T1 - Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine

AU - Kamp, Verena Te

AU - Friedrichs, Virginia

AU - Freuling, Conrad M.

AU - Vos, Ad

AU - Potratz, Madlin

AU - Klein, Antonia

AU - Zaeck, Luca M.

AU - Eggerbauer, Elisa

AU - Schuster, Peter

AU - Kaiser, Christian

AU - Ortmann, Steffen

AU - Kretzschmar, Antje

AU - Bobe, Katharina

AU - Knittler, Michael R.

AU - Dorhoi, Anca

AU - Finke, Stefan

AU - Müller, Thomas

N1 - Funding Information: Funding: The project was funded in the frame of a research cooperation with IDT Biologika GmbH (now Ceva Santé Animale, France) into mechanisms of oral rabies vaccination. Parts of the project were supported by an intramural collaborative research grant at the Friedrich-Loeffler-Institut. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/1/14

Y1 - 2021/1/14

N2 - The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre-and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

AB - The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre-and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

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ER -

Comparable long-term rabies immunity in foxes after intramuscular and oral application using a third-generation oral rabies virus vaccine

Abstract

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