Skip to main content
Log in

Experimental challenge of horses after prime-boost immunization with a modified live equid alphaherpesvirus 1 vaccine administered by two different routes

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The immune response and protective efficacy of a modified equid alphaherpesvirus 1 (EHV-1) vaccine administered by two different routes were tested in horses. Horses that received intramuscular (IM) priming and an intranasal (IN) booster with a 28-day interval (IM-IN group [n = 6]), IN priming and IM booster (IN-IM group [n = 5]), or no vaccination (control group [n = 6]) were challenged with EHV-1 strain 10-I-224 28 days after the second vaccination. Both vaccinated groups had significantly higher serum virus-neutralizing titers than the control group, with increased levels of serum IgGa, IgGb, and IgA antibodies (p < 0.05). The nasal antibody response was dominated by the IgGa and IgGb subclasses in both vaccinated groups, with no IgA antibody response. After challenge infection, three of six control horses were pyretic for 1-4 days post-inoculation (dpi), whereas none in the vaccinated groups were pyretic during this period. The number of horses that were pyretic at 5-10 dpi was 4 out of 6 for the controls, 3 out of 6 for the IM-IN group, and 2 out of 5 for the IN-IM group. Nasal virus replication in the IN-IM group (3-4 dpi) and IM-IN group (3 dpi) was significantly lower than in the control group (p < 0.05). All of the control horses showed viremia, whereas two horses in the IM-IN group and one in the IN-IM group did not. In conclusion, although IM-IN or IN-IM vaccination did not elicit a mucosal IgA response, it provided partial protection at a level similar to that of the conventional program, likely due to systemic antibodies and mucosal IgG subclass responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Patel JR, Heldens J (2005) Equine herpesviruses 1 (EHV-1) and 4 (EHV-4)—epidemiology, disease and immunoprophylaxis: a brief review. Vet J 170:14–23

    Article  CAS  Google Scholar 

  2. Goehring LS, Wagner B, Bigbie R, Hussey SB, Rao S, Morley PS, Lunn DP (2010) Control of EHV-1 viremia and nasal shedding by commercial vaccines. Vaccine 28:5203–5211

    Article  CAS  Google Scholar 

  3. Goodman LB, Wagner B, Flaminio MJBF, Sussman KH, Metzger SM, Holland R, Osterrieder N (2006) Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1). Vaccine 24:3636–3645

    Article  CAS  Google Scholar 

  4. Heldens JGM, Hannant D, Cullinane AA, Prendergast MJ, Mumford JA, Nelly M, Kydd JH, Weststrate MW, van den Hoven R (2001) Clinical and virological evaluation of the efficacy of an inactivated EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in foals and pregnant mares. Vaccine 19:4307–4317

    Article  CAS  Google Scholar 

  5. Bannai H, Tsujimura K, Kondo T, Nemoto M, Yamanaka T, Sugiura T, Maeda K, Matsumura T (2011) Induction of a Th-1-biased IgG subclass response against equine herpesvirus type 1 in horses previously infected with type 4 virus. J Vet Med Sci 73:535–539

    Article  Google Scholar 

  6. Breathnach CC, Yeargan MR, Sheoran AS, Allen GP (2001) The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens. Equine Vet J 33:651–657

    Article  CAS  Google Scholar 

  7. Patel JR, Bateman H, Williams J, Didlick S (2003) Derivation and characterisation of a live equid herpes virus-1 (EHV-1) vaccine to protect against abortion and respiratory disease due to EHV-1. Vet Microbiol 91:23–39

    Article  CAS  Google Scholar 

  8. Patel JR, Földi J, Bateman H, Williams J, Didlick S, Stark R (2003) Equid herpesvirus (EHV-1) live vaccine strain C147: efficacy against respiratory diseases following EHV types 1 and 4 challenges. Vet Microbiol 92:1–17

    Article  CAS  Google Scholar 

  9. Patel JR, Didlick S, Bateman H (2004) Efficacy of a live equine herpesvirus-1 (EHV-1) strain C147 vaccine in foals with maternally-derived antibody: protection against EHV-1 infection. Equine Vet J 36:447–451

    Article  CAS  Google Scholar 

  10. Slater JD, Gibson JS, Field HJ (1993) Pathogenicity of a thymidine kinase-deficient mutant of equine herpesvirus 1 in mice and specific pathogen-free foals. J Gen Virol 74:819–828

    Article  CAS  Google Scholar 

  11. Tewari D, Gibson JS, Slater JD, O’Neill T, Hannant D, Allen GP, Field HJ (1993) Modulation of the serological response of specific pathogen-free (EHV-free) foals to EHV-1 by previous infection with EHV-4 or a TK-deletion mutant of EHV-1. Arch Virol 132:101–120

    Article  CAS  Google Scholar 

  12. Bannai H, Nemoto M, Tsujimura K, Yamanaka T, Kokado H, Kondo T, Matsumura T (2018) Comparison of protective efficacies between intranasal and intramuscular vaccination of horses with a modified live equine herpesvirus type-1 vaccine. Vet Microbiol 222:18–24

    Article  CAS  Google Scholar 

  13. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B (2018) Deletion of the ORF2 of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity. BMC Vet Res 14:245

    Article  Google Scholar 

  14. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B (2019) An equine herpesvirus type 1 (EHV-1) Ab4 open reading frame 2 deletion mutant provides immunity and protection from EHV-1 infection and disease. J Virol 93:e01011-e1019

    Article  CAS  Google Scholar 

  15. Lapuente D, Fuchs J, Willar J, Antao AV, Eberlein V, Uhlig N, Issmail L, Schmidt A, Oltmanns F, Peter AS, Mueller-Schmucker S, Irrgang P, Fraedrich K, Cara A, Hoffmann M, Pohlmann S, Ensser A, Pertl C, Willert T, Thirion C, Grunwald T, Uberla K, Tenbusch M (2021) Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization. Nat Commun 12:6871

    Article  CAS  Google Scholar 

  16. Mantis NJ, Kozlowski PA, Mielcarz DW, Weissenhorn W, Neutra MR (2001) Immunization of mice with recombinant gp41 in a systemic prime/mucosal boost protocol induces HIV-1-specific serum IgG and secretory IgA antibodies. Vaccine 19:3990–4001

    Article  CAS  Google Scholar 

  17. Yuan L, Azevedo MSP, Gonzalez AM, Jeong K, Nguyen TV, Lewis P, Iosef C, Herrmann JE, Saif L (2005) Mucosal and systemic antibody responses and protection induced by a prime/boost rotavirus-DNA vaccine in a gnotobiotic pig model. Vaccine 23:3925–3936

    Article  CAS  Google Scholar 

  18. Crouch CF, Daly J, Henley W, Hannant D, Wilkins J, Francis MJ (2005) The use of a systemic prime/mucosal boost strategy with an equine influenza ISCOM vaccine to induce protective immunity in horses. Vet Immunol Immunopathol 108:345–355

    Article  CAS  Google Scholar 

  19. Hannant D, Easeman R, Mumford JA (1998) Equine mucosal immune system: Intranasal vaccination with inactivated equine influenza virus protects from infection. In: Wernery U, Wade JF, Mumford JA, Kaaden OR (eds) Equine infectious diseases VIII. R&W Publications, Newmarket, pp 50–56

    Google Scholar 

  20. Matsumura T, Sugiura T, Imagawa H, Fukunaga Y, Kamada M (1992) Epizootiological aspects of type 1 and type 4 equine herpesvirus infections among horse populations. J Vet Med Sci 54:207–211

    Article  CAS  Google Scholar 

  21. Kawakami Y, Nakano K, Kume T, Hiramune T, Murase N (1970) Abortion by equine rhinopneumonitis virus in Hidaka, Hokkaido district in Japan. Bull Natl Inst Anim Health 61:9–16 (in Japanese)

    Google Scholar 

  22. Andoh K, Takasugi M, Mahmoud HYAH, Hattori S, Terada Y, Noguchi K, Shimoda H, Bannai H, Tsujimura K, Matsumura T, Kondo T, Maeda K (2013) Identification of a major immunogenic region of equine herpesvirus-1 glycoprotein E and its application to enzyme-linked immunosorbent assay. Vet Microbiol 164:18–26

    Article  CAS  Google Scholar 

  23. Bannai H, Nemoto M, Tsujimura K, Yamanaka T, Maeda K, Kondo T (2016) Improvement of an enzyme-linked immunosorbent assay for equine herpesvirus type 4 by using a synthetic-peptide 24-mer repeat sequence of glycoprotein G as an antigen. J Vet Med Sci 78:309–311

    Article  CAS  Google Scholar 

  24. Bannai H, Nemoto M, Tsujimura K, Yamanaka T, Kondo T, Matsumura T (2013) Development of a focus-reduction neutralizing test for detecting equine herpesvirus type-1-neutralizing antibodies. J Vet Med Sci 75:1209–1212

    Article  Google Scholar 

  25. Bannai H, Tsujimura K, Nemoto M, Ohta M, Yamanaka T, Kokado H, Matsumura T (2019) Epizootiological investigation of equine herpesvirus type 1 infection among Japanese racehorses before and after the replacement of an inactivated vaccine with a modified live vaccine. BMC Vet Res 15:280

    Article  Google Scholar 

Download references

Acknowledgments

We thank Akira Kokubun, Akiko Kasagawa, Akiko Suganuma, Miwa Tanaka, Kaoru Watanabe, and Kayo Iino at the Equine Research Institute for providing technical assistance.

Funding

This study was funded by the Japan Racing Association (Tokyo, Japan).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: HB and KT. Investigation: HB, YK, MN and KT. Methodology: MN, MO and KT. Project administration: MO and KT. Supervision: HB. Writing—original draft: HB and YK; Writing—review and editing: HB, YK, MN, MO and KT.

Corresponding author

Correspondence to Hiroshi Bannai.

Ethics declarations

Conflict of interest

The authors have no relevant or non-financial interests to disclose.

Ethical approval

The ethics of this study were approved by the Ethics and Research Promotion Committee of the Equine Research Institute of the Japan Racing Association (approval number 2018-3263-07).

Additional information

Handling Editor: Ana Cristina Bratanich.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 14 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bannai, H., Kambayashi, Y., Nemoto, M. et al. Experimental challenge of horses after prime-boost immunization with a modified live equid alphaherpesvirus 1 vaccine administered by two different routes. Arch Virol 168, 27 (2023). https://doi.org/10.1007/s00705-022-05638-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00705-022-05638-w

Navigation