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Vaccine2019; 37(10); 1299-1306; doi: 10.1016/j.vaccine.2019.01.053

Serum antibody immunoreactivity and safety of native porcine and recombinant zona pellucida vaccines formulated with a non-Freund’s adjuvant in horses.

Abstract: Commercial and regulatory limitations associated with native porcine zona pellucida (pZP) vaccines formulated with Freund's adjuvants may be overcome by developing effective recombinant ZP vaccines (reZP) and identifying alternative adjuvant formulations. A two-part preparatory study used 15 geldings and identified potentially effective alternative adjuvant formulations based on anti-pZP antibody response following treatment with pZP formulated with Addavax (AddaVax ™, Invivogen), Quil A (Quil-A® Adjuvant, Invivogen), Quil A and Poly (I:C) (HMW VacciGrade™, Invivogen), Pet Gel A (Montanide™ Pet Gel A, Seppic) and Pet Gel A and Poly (I:C). Injection site reactions, rectal temperature and respiratory and heart rates were also monitored for three days post-treatment. Suitable anti-pZP antibody titres were seen in response to Pet Gel A and Pet Gel A and Poly (I:C). Subsequently in 31 mares, following administration of pZP, reZP and a combination of pZP and reZP proteins prepared in Pet Gel A and Poly (I:C), both serum anti-pZP and -reZP antibody responses were monitored. In addition, safety was assessed for up to seven days post-treatment by inspection and palpation of gluteal intramuscular injection sites and measurement of rectal temperature. The measured antibody titres in all treatment groups differed significantly to an adjuvant control group (P  0.05). Side effects were mild and transient in nature. This represents the first application of a reZP vaccine formulated with non-Freund's adjuvants evoking a similar antibody titre response to native pZP vaccination in mares.
Publication Date: 2019-02-04 PubMed ID: 30733089DOI: 10.1016/j.vaccine.2019.01.053Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores alternatives to traditionally used adjuvants in vaccines for horses, specifically looking at native porcine zona pellucida (pZP) and recombinant ZP (reZP) vaccines. The study found that a newly tested reZP vaccine formulated with an alternative adjuvant produced similar immune responses to traditional pZP vaccines with limited side-effects, marking the first time these results have been achieved in mares.

Objective of the Research

The main objective of the research was to find an alternative to the Freund’s adjuvants that are commonly used in native porcine zona pellucida (pZP) vaccines due to limitations associated with their commercial and regulatory use. The focus was on developing effective recombinant ZP (reZP) vaccines and testing adjuvant formulations that could evoke similar immune response as the traditionally used pZP vaccines.

Methodology

  • The researchers conducted a two-part study involving 15 geldings and 31 mares. In the initial stage, numerous alternative adjuvant formulations such as Addavax, Quil A, Quil A and Poly (I:C), Pet Gel A, and Pet Gel A and Poly (I:C) were tested on geldings. The horses’ anti-pZP antibody response, injection site reactions, rectal temperature, and heart and respiratory rates were monitored post-treatment.
  • In the second part of the study, the researchers administered pZP, reZP, and a combination of both, prepared in Pet Gel A and Poly (I:C) to 31 mares. Post inoculation, they monitored the serum anti-pZP and -reZP antibody responses. They also assessed the safety of the treatment by inspecting the injection sites and measuring rectal temperature for a week post-treatment.

Results

  • The researchers found that Pet Gel A and Pet Gel A and Poly (I:C) elicited suitable anti-pZP antibody responses in the first phase of the experiment.
  • In the second phase, all treatment groups (pZP, reZP, and the combination) elicited a significant antibody response compared to an adjuvant control group.
  • The temporal changes in both anti-pZP and -reZP antibody titres in all the groups were similar to patterns reported in other species vaccinated with pZP formulated with Freund’s adjuvants.
  • There was no significant difference in anti-pZP antibody titres between the groups treated with pZP and reZP.
  • The side effects observed were mild and temporary, suggesting the alternative was safe for use.

Conclusions

The researchers concluded that a reZP vaccine formulated with non-Freund’s adjuvants can elicit a similar immune response to native pZP vaccination. This is the first time this effect has been found in mares, which indicates a possible alternative to the traditionally used Freund’s adjuvants in pZP vaccines for horses, overcoming commercial and regulatory constraints.

Cite This Article

APA
Nolan MB, Schulman ML, Botha AE, Human AM, Roth R, Crampton MC, Bertschinger HJ. (2019). Serum antibody immunoreactivity and safety of native porcine and recombinant zona pellucida vaccines formulated with a non-Freund’s adjuvant in horses. Vaccine, 37(10), 1299-1306. https://doi.org/10.1016/j.vaccine.2019.01.053

Publication

ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 37
Issue: 10
Pages: 1299-1306
PII: S0264-410X(19)30129-X

Researcher Affiliations

Nolan, Margaret B
  • Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa; Veterinary Population Management Laboratory, Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Electronic address: margaret.nolan@up.ac.za.
Schulman, Martin L
  • Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa; Veterinary Population Management Laboratory, Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Electronic address: martin.schulman@up.ac.za.
Botha, Alma E
  • Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Electronic address: ester.botha@up.ac.za.
Human, Anne-Marie
  • Veterinary Population Management Laboratory, Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Electronic address: annemarie.human@up.ac.za.
Roth, Robyn
  • Biomanufacturing Technologies, Biosciences, Council for Scientific and Industrial Research, Pretoria, South Africa. Electronic address: rroth@csir.co.za.
Crampton, Michael C
  • Biomanufacturing Technologies, Biosciences, Council for Scientific and Industrial Research, Pretoria, South Africa. Electronic address: mcrampton@csir.co.za.
Bertschinger, Henk J
  • Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa; Veterinary Population Management Laboratory, Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa. Electronic address: henkbert@tiscali.co.za.

MeSH Terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Animals
  • Antibody Formation
  • Horses / immunology
  • Male
  • Swine
  • Vaccines, Contraceptive / administration & dosage
  • Vaccines, Contraceptive / immunology
  • Zona Pellucida / immunology

Citations

This article has been cited 6 times.
  1. Carnet F, Perrin-Cocon L, Paillot R, Lotteau V, Pronost S, Vidalain PO. An inventory of adjuvants used for vaccination in horses: the past, the present and the future.. Vet Res 2023 Mar 2;54(1):18.
    doi: 10.1186/s13567-023-01151-3pubmed: 36864517google scholar: lookup
  2. French H, Segabinazzi L, Middlebrooks B, Peterson E, Schulman M, Roth R, Crampton M, Conan A, Marchi S, Gilbert T, Knobel D, Bertschinger H. Efficacy and Safety of Native and Recombinant Zona Pellucida Immunocontraceptive Vaccines Formulated with Non-Freund's Adjuvants in Donkeys.. Vaccines (Basel) 2022 Nov 24;10(12).
    doi: 10.3390/vaccines10121999pubmed: 36560409google scholar: lookup
  3. Aurich C, Kaps M. Suppression of reproductive behaviour and gonadal function in female horses-An update.. Reprod Domest Anim 2022 Sep;57 Suppl 4(Suppl 4):4-12.
    doi: 10.1111/rda.14129pubmed: 35467049google scholar: lookup
  4. Peterson EW, Segabinazzi LGTM, Gilbert RO, Bergfelt DR, French HM. Evaluation of Stress Accompanying Immunocontraceptive Vaccination in Donkeys.. Animals (Basel) 2022 Feb 13;12(4).
    doi: 10.3390/ani12040457pubmed: 35203165google scholar: lookup
  5. Tatematsu KI, Ikeda M, Wakabayashi Y, Yamamura T, Kikuchi K, Noguchi J, Sezutsu H. Silkworm recombinant bovine zona pellucida protein 4 (bZP4) as a potential female immunocontraceptive antigen; impaired sperm-oocyte interaction and ovarian dysfunction.. J Reprod Dev 2021 Dec 14;67(6):402-406.
    doi: 10.1262/jrd.2021-103pubmed: 34670878google scholar: lookup
  6. Wu X, Yang Y, Kling C, Seigler L, Gallardo-Romero NF, Martin BE, Smith TG, Olson VA. Inactivated Rabies Virus-Vectored Immunocontraceptive Vaccine in a Thermo-Responsive Hydrogel Induces High and Persistent Antibodies against Rabies, but Insufficient Antibodies against Gonadotropin-Releasing Hormone for Contraception.. Vaccines (Basel) 2019 Jul 25;7(3).
    doi: 10.3390/vaccines7030073pubmed: 31349649google scholar: lookup