Shalash Ahmed O, Wang Wanyi, Xia Yihui, Hussein Waleed M, Bashiri Sahra, D'Occhio Michael J, Stephenson Rachel J, Skwarczynski Mariusz, Toth Istvan
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
Vaccine. 2025 Apr 19;53:127092. doi: 10.1016/j.vaccine.2025.127092. Epub 2025 Apr 4.
Immunocontraceptive vaccines targeting gonadotropin-releasing hormone (GnRH) are in high demand for controlling population growth and managing the temperament of both wild and domesticated animals. Achieving adequate efficacy, especially with a single-dose immunization, requires potent vaccines and adjuvants. However, commercial vaccines face challenges: some, like Gonacon®, have regulatory issues with veterinary authorities, while others, like Bopriva®, lack potency and require multiple booster doses. Thus, there is a critical need for highly effective vaccines with robust adjuvants suitable for easy, less invasive single-dose administration. Recent studies have shown that peptide vaccines adjuvanted with 15-mer polyleucine (L) or poly(methyl acrylate) (PMA) demonstrate potent immunogenicity, comparable to complete Freund's adjuvant (CFA), after a single dose against Streptococcus pyogenes. Our research aims to evaluate the performance of these promising vaccine adjuvant as single-dose contraceptive vaccines in mice, compared to well-established commercial and experimental adjuvants, such as AddaVax®, Incomplete Freunds Adjuvant (IFA), and CFA. To develop a vaccine with sufficient HLA coverage for cattle immunocontraception, we evaluated a peptide vaccine incorporating three cattle-compatible helper T cell epitopes. We evaluated the immunogenicity of constructs in mice to that of a construct with the universal mouse-compatible PADRE (P) helper T cell epitope. Various vaccines were prepared to investigate: (A) the impact of incorporating cattle-compatible helper T cells on immunogenicity, and (B) the effectiveness of different adjuvant systems compared to CFA. The vaccines were administered subcutaneously to C57BL/6 mice, and serological assays revealed that the L/Quil A-based vaccine system was highly immunogenic, with performance comparable to CFA without the need for reactogenic mycobacterial components. Our vaccines significantly reduced serum progesterone levels in mice, making the L/Quil A system a strong candidate for single-dose anti-fertility application, followed by PMA, and AddaVax® adjuvanted GnRH.
针对促性腺激素释放激素（GnRH）的免疫避孕疫苗在控制人口增长以及管理野生动物和家畜性情方面有很高的需求。要实现足够的效力，尤其是单剂量免疫时，需要强效疫苗和佐剂。然而，商业疫苗面临挑战：一些疫苗，如Gonacon®，在兽医当局存在监管问题，而其他疫苗，如Bopriva®，效力不足且需要多次加强剂量。因此，迫切需要具有强效佐剂的高效疫苗，适合简便、侵入性较小的单剂量给药。最近的研究表明，用15聚亮氨酸（L）或聚丙烯酸甲酯（PMA）佐剂的肽疫苗在单剂量接种抗化脓性链球菌后显示出与完全弗氏佐剂（CFA）相当的强效免疫原性。我们的研究旨在评估这些有前景的疫苗佐剂作为单剂量避孕疫苗在小鼠中的性能，并与成熟的商业和实验佐剂（如AddaVax®、不完全弗氏佐剂（IFA）和CFA）进行比较。为开发一种对牛免疫避孕具有足够HLA覆盖的疫苗，我们评估了一种包含三个牛兼容辅助性T细胞表位的肽疫苗。我们在小鼠中评估构建体的免疫原性，并与具有通用小鼠兼容PADRE（P）辅助性T细胞表位的构建体进行比较。制备了各种疫苗以研究：（A）加入牛兼容辅助性T细胞对免疫原性的影响，以及（B）与CFA相比不同佐剂系统的有效性。将疫苗皮下注射给C57BL/6小鼠，血清学检测表明基于L/Quil A的疫苗系统具有高度免疫原性，其性能与CFA相当，且无需产生反应原性的分枝杆菌成分。我们的疫苗显著降低了小鼠血清孕酮水平，使L/Quil A系统成为单剂量抗生育应用的有力候选者，其次是PMA和AddaVax®佐剂的GnRH。
