Chundru Dhiraj, Bhattrai Shailes, Timilsina Madhusudan, Lillehoj Hyun, Sun Zhifeng, Ghanem Mostafa, Li Charles
Department of Veterinary Medicine, Virginia-Maryland College of Veterinary Medicine, Maryland Campus, College Park, MD 20740, USA.
Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service-US Department of Agriculture, Beltsville, MD 20705, USA.
Microorganisms. 2025 May 16;13(5):1147. doi: 10.3390/microorganisms13051147.
Necrotic enteritis (NE), caused by pathogenic , poses a significant threat to global poultry health, with estimated annual losses exceeding USD 6 billion. The rising incidence of NE has been associated with the reduced use of antibiotic growth promoters, underscoring the urgent need for alternative control measures such as vaccination. Collagen adhesin protein (CNA), a key virulence factor in NE pathogenesis, represents a promising vaccine target. The US Food and Drug Administration has begun phasing out animal testing requirements for biologics and monoclonal antibody drugs. In this study, a computational multi-epitope vaccine (MEV) targeting CNA was designed by integrating predicted Cluster of Differentiation (CD)4 helper T lymphocyte (Th), CD8 cytotoxic T lymphocyte (CTL), and B-cell epitopes. Bioinformatics tools were used to identify immunogenic, antigenic, and non-allergenic epitopes assembled into a 115-amino-acid peptide vaccine construct. The candidate demonstrated strong stability and solubility. In silico immune simulation predicted robust immune responses, including elevated IgG and IgM antibody levels, plasma cell proliferation, Th memory formation, and CTL activation, comparable to responses elicited by a full-length CNA. These findings support the potential of the designed peptide as one of the multiple effective NE vaccine components, offering a promising alternative to antibiotic-based approaches in poultry disease management.
坏死性肠炎（NE）由致病性因素引起，对全球家禽健康构成重大威胁，估计每年损失超过60亿美元。NE发病率的上升与抗生素生长促进剂使用的减少有关，这突出表明迫切需要诸如疫苗接种等替代控制措施。胶原蛋白粘附蛋白（CNA）是NE发病机制中的关键毒力因子，是一个有前景的疫苗靶点。美国食品药品监督管理局已开始逐步取消对生物制品和单克隆抗体药物的动物试验要求。在本研究中，通过整合预测的分化簇（CD）4辅助性T淋巴细胞（Th）、CD8细胞毒性T淋巴细胞（CTL）和B细胞表位，设计了一种靶向CNA的计算多表位疫苗（MEV）。利用生物信息学工具鉴定出免疫原性、抗原性和非致敏性表位，组装成一个115个氨基酸的肽疫苗构建体。该候选物表现出很强的稳定性和溶解性。计算机免疫模拟预测了强烈的免疫反应，包括IgG和IgM抗体水平升高、浆细胞增殖、Th记忆形成和CTL激活，与全长CNA引发的反应相当。这些发现支持了所设计肽作为多种有效的NE疫苗成分之一的潜力，为家禽疾病管理中基于抗生素的方法提供了一个有前景的替代方案。
