BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1(-/-) Mice from Monkeypoxvirus Lethal...

Area of Science:

• Virology
• Vaccinology
• Biotechnology

Background:

• Monkeypox virus (MPXV) causes human monkeypox (MPX), an emerging zoonotic disease in Africa with potential for human-to-human transmission.
• Declining smallpox vaccination coverage leaves populations vulnerable to MPXV.
• Lack of approved MPX therapies and safety concerns with current vaccines necessitate novel prophylactic strategies.

Purpose of the Study:

• To evaluate a new vaccination strategy using recombinant bovine herpesvirus 4 (BoHV-4) vectors expressing MPXV glycoproteins.
• To assess the protective efficacy of these BoHV-4 vectors against a lethal MPXV challenge in a mouse model.

Main Methods:

• Construction of three recombinant BoHV-4 vectors (BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4-A-EF1α-M1RgD106ΔTK, and BoHV-4-A-EF1α-B6RgD106ΔTK) expressing MPXV glycoproteins (A29L, M1R, B6R) via recombineering.
• Demonstration of transgene expression and safety assessment of the recombinant BoHV-4 vectors following intraperitoneal administration in STAT1 knockout mice.
• Evaluation of protection against lethal MPXV challenge using individual vectors or combinations.

Main Results:

• All three recombinant BoHV-4 vectors were successfully constructed and demonstrated transgene expression.
• The recombinant BoHV-4 vectors were found to be safe, with no adverse events observed in mice.
• BoHV-4-A-EF1α-M1RgD106ΔTK alone provided 100% protection, while a combination of vectors achieved 80% protection against MPXV-induced mortality and morbidity in STAT1(-/-) mice.

Conclusions:

• Recombinant BoHV-4 vectors expressing MPXV glycoproteins are effective in protecting against lethal MPXV challenge.
• BoHV-4 serves as a promising vaccine-vector platform for developing MPXV prophylaxis.
• This study highlights the potential of BoHV-4 based vaccines for controlling MPXV outbreaks.