Coated Bacterial Vaccine Platform Overcomes Weak Antigen Immunogenicity: A Functional Approach to GnRH-Based Immunocastration

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Abstract
Immunocastration, a non-surgical strategy based on active immunization against gonadotropin-releasing hormone (GnRH), effectively suppresses steroidogenesis and spermatogenesis. However, peptide vaccines targeting poorly immunogenic antigens such as GnRH often fail to elicit robust adaptive immune responses, requiring adjuvants or carrier proteins. Previously, we introduced Coated Bacterial Vaccines (CBVs), a platform that uses chemically inactivated Gram-positive bacteria to display recombinant antigens fused to the SlpA carboxy-terminal domain (dSLPA) on their surface. This system leverages natural pathogen-associated molecular patterns (PAMPs) to enhance immunogenicity without additional adjuvants. In this work, we extended the application of the CBVs platform to enhance the immune response against a poorly immunogenic GnRH-based peptide vaccine. GnRH-CBVs were formulated using inactivated Bacillus subtilis var. natto coated with a recombinant GnRH tandem-repeat–dSLPA fusion protein and administered to male BALB/c mice. A chitosan-adjuvanted GnRH-dSLPA formulation served as a positive control. GnRH-CBVs induced a strong Th2-biased humoral response, characterized by predominant IgG1 levels comparable to those achieved with chitosan. The resulting antibodies effectively neutralized endogenous GnRH, reducing steroidogenesis and spermatogenesis and inducing marked testicular histological alterations. These findings support CBVs as a promising strategy to enhance peptide vaccine immunogenicity for veterinary immunocastration.
Funding Information
  • National Agency for the Promotion of Research ANPCyT (PICT 2019-3123)
  • National Agency for the Promotion of Research ANPCyT (PICT 2019-2402)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (PIBAA-CONICET 2022)
  • Biogénesis Bagó S.A. (R&D Agreement RD-EX-2024-23226366)

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