The p15 protein is a promising immunogen for developing protective immunity against African swine fever virus
image: The structure of p15 in complex with neutralizing antibody
Credit: Qi Yu, Wangjun Fu, Zhenjiang Zhang, Dening Liang, Lulu Wang, Yuanmao Zhu, Encheng Sun, Fang Li, Zhigao Bu, Yutao Chen, Xiangxi Wang, Dongming Zhao
The main text describes the production and characterization of monoclonal antibodies against p15, the structural analysis of the p15-4E2 complex, and the construction and evaluation of p15-VLPs. Researchers used ELISA, ELISpot, and cryo-electron microscopy (cryo-EM) to study the immune responses and structural details. Pigs were immunized with p15 or p15-VLPs and challenged with ASFV to assess protection.
Key findings from the study include:
- Neutralizing Antibody Identification: A high-affinity monoclonal antibody, 4E2, was identified against p15, exhibiting potent neutralizing activity in vitro. The antibody binds to a specific epitope on p15, primarily interacting with the a4 helix and B-sheet tail of the p15 monomer.
- Structural Insights: The structure of the p15-4E2 complex was determined at 3.75 Å resolution, revealing the precise nature of the p15 epitope. The complex retains the α-helical packed head formed by the five N-terminal α-helices of p15.
- VLP Construction and Evaluation: Two types of p15-VLPs (p15-I3 and p15-I53-50AB) were constructed and shown to efficiently assemble into target icosahedral structures. Pigs immunized with p15-VLPs exhibited higher antibody responses compared to those immunized with individual p15.
- Protective Efficacy: Immunization with p15 or p15-VLPs provided effective protection against a moderately virulent ASFV strain, with all immunized pigs surviving the challenge and showing reduced viral loads in blood and tissues.
This study demonstrates that the p15 protein is a promising immunogen for developing ASF vaccines. The identification of a high-affinity neutralizing antibody, 4E2, and the structural analysis of the p15-4E2 complex provide valuable insights into the biological properties of p15. The construction and evaluation of p15-VLPs further support the potential of p15 as a vaccine candidate. However, single-use of p15 may not be sufficient against highly virulent strains, highlighting the need for coordinated immune responses against multiple critical viral proteins. The work entitled “ The p15 Protein is a Promising Immunogen for Developing Protective Immunity Against African Swine Fever Virus” was published on Protein & Cell (published on Apr. 15, 2025).