Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Smallpox eradication via vaccination has been achieved, but bioterrorism threats necessitate renewed vaccination efforts.
• Outbreaks of monkeypox and other zoonotic orthopoxviruses highlight ongoing public health concerns.
• Traditional vaccinia virus vaccines pose health risks due to their live virus nature.

Purpose of the Study:

• To evaluate the efficacy of a DNA subunit vaccine against monkeypox virus challenge.
• To determine if a DNA vaccine targeting specific vaccinia virus genes can provide protection.

Main Methods:

• Rhesus macaques were vaccinated with a DNA vaccine encoding four vaccinia virus genes (L1R, A27L, A33R, B5R) or a single gene (L1R).
• Vaccinated animals were subsequently challenged with a lethal dose of monkeypox virus.
• Protection was assessed by monitoring disease severity and survival rates.

Main Results:

• Macaques vaccinated with the four-gene DNA vaccine were protected from severe disease following monkeypox virus challenge.
• Animals vaccinated with the single L1R gene vaccine experienced severe disease but survived.
• This study demonstrates the feasibility of a subunit vaccine approach for smallpox and monkeypox.

Conclusions:

• A DNA subunit vaccine targeting multiple vaccinia virus genes offers significant protection against monkeypox.
• This approach represents a potentially safer alternative to live vaccinia virus vaccines.
• Further development of subunit vaccines could mitigate risks associated with orthopoxvirus infections.