AUTHOR=Tesfaye Adehanom Baraki , Han Rui , Tao Zhengyu , You Liuchao , Zhu Jiayao , Gao Pengcheng , Fu Lei , Chu Yuefeng TITLE=Review of advanced research on swine Actinobacillus pleuropneumoniae vaccine development strategy JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1645610 DOI=10.3389/fimmu.2025.1645610 ISSN=1664-3224 ABSTRACT=Actinobacillus pleuropneumoniae (App) infection is a major respiratory disease that causes severe economic losses. It is highly infectious and exhibits multiple serotypes, which complicates prevention and control. This review discusses the new-generation vaccine development strategies and the role of virulence factors—such as App toxins, capsular polysaccharide (CPS), lipopolysaccharide (LPS), and outer membrane proteins (OMPs)—in vaccine design. Traditional vaccines offer limited cross-protection, whereas live attenuated vaccines, subunit vaccines, and toxin-based vaccines show promising improvements in efficacy and safety. Current and near-generation subunit and toxin vaccines mainly focus on conserved antigens, incorporating App toxins, OMPs ApfA, and GALT, which significantly enhance cross-protection and safety. Other approaches, including DNA vaccines and combined multivalent vaccines targeting highly prevalent App serotypes and integrating antigens from other pathogens, represent a modern strategy aimed at enhancing cross-serotype protection, minimizing side effects, and enabling differentiating infected from vaccinated animal (DIVA) capability.