Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus

• Published in: Vaccine 2024-02, Vol.42 (4), p.828-839
• Main Authors: Guo, Weilu, Wang, Chuanhong, Song, Xu, Xu, Hong, Zhao, Shuqing, Gu, Jun, Zou, Zhikun, Li, Jing, Qian, Jiali, Zhang, Xue, Guo, Rongli, Li, Jizong, Li, Li, Hu, Zhaoyang, Ren, Lili, Fan, Baochao, Li, Bin
• Format: Article
• Language: English
• Subjects: Adjuvants; Amino acids; Animal husbandry; Antibodies; Antigens; Biotechnology; Blood; CD19 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Cell proliferation; Commercialization; Diarrhea; Economic impact; Epidemics; Epitopes; Full-length S protein; Hogs; Immunization; Immunoassays; Immunogenicity; Immunoglobulin A; Immunoglobulin G; Interleukin 4; Intestine; Leukocytes (mononuclear); Lymphocytes; Lymphocytes B; Lymphocytes T; Membranes; Natural killer cells; Neutralizing; PEDV; Peripheral blood mononuclear cells; Plasmids; Protection; Proteins; Subunit vaccines; Swine; Transmissible gastroenteritis; Trimeric; Trimers; Vaccines; Viruses; γ-Interferon
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2024.01.020

•Trimeric S, S1, COEs, and two adjuvants were selected to evaluate immune effects.•S/M103 elicited neutralizing antibodies, T cells, B cells, and NK cells in mice.•S/M103 induced high levels of neutralizing antibodies, IFN-γ, and IL-4 in piglets.•S/M103 provided protection against viral challenge in piglets. Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.