A Cell-Adapted Live-Attenuated Vaccine Candidate Protects Pigs against the Homologous Strain VNUA-ASFV-05L1, a Representative Strain of the Contemporary Pandemic African Swine Fever Virus
Quang Lam Truong,
Lihua Wang,
Tuan Anh Nguyen,
Hoa Thi Nguyen,
Son Danh Tran,
Anh Thi Vu,
Anh Dao Le,
Van Giap Nguyen,
Phuong Thi Hoang,
Yen Thi Nguyen,
Thi Luyen Le,
Thang Nguyen Van,
Thi My Le Huynh,
Huong Thi Lan Lai,
Rachel Madera,
Yuzhen Li,
Jishu Shi,
Lan Thi Nguyen
Affiliations
Quang Lam Truong
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Lihua Wang
Center on Vaccine Evaluation and Alternatives for Antimicrobials, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Tuan Anh Nguyen
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Hoa Thi Nguyen
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Son Danh Tran
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Anh Thi Vu
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Anh Dao Le
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Van Giap Nguyen
Department of Veterinary Microbiology and Infectious Diseases, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Phuong Thi Hoang
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Yen Thi Nguyen
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Thi Luyen Le
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Thang Nguyen Van
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Thi My Le Huynh
Department of Veterinary Microbiology and Infectious Diseases, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Huong Thi Lan Lai
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
Rachel Madera
Center on Vaccine Evaluation and Alternatives for Antimicrobials, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Yuzhen Li
Center on Vaccine Evaluation and Alternatives for Antimicrobials, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Jishu Shi
Center on Vaccine Evaluation and Alternatives for Antimicrobials, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Lan Thi Nguyen
Key Laboratory of Veterinary Biotechnology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Gia Lam, Ha Noi 12406, Vietnam
African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 102 HAD50, to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 102 to 105 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.
