A protein-based smallpox vaccine protects non-human primates from a lethal monkeypox virus challenge

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Orthopoxvirus infections, including smallpox and monkeypox, pose significant public health concerns.
• Existing vaccines have limitations, necessitating the development of safer and more effective alternatives.
• Subunit vaccines present a promising avenue for improved safety profiles.

Purpose of the Study:

• To evaluate the efficacy of a novel subunit smallpox vaccine against orthopoxvirus challenge.
• To assess the role of CpG adjuvant in enhancing vaccine-induced protection.
• To investigate the immunological correlates of protection.

Main Methods:

• A subunit vaccine composed of vaccinia virus membrane proteins (A33, B5, L1, A27) was formulated with aluminum hydroxide (alum) ± CpG adjuvant.
• Non-human primates were immunized with the subunit vaccine.
• Immunized animals were subsequently challenged with a lethal intravenous dose of monkeypox virus.
• Humoral immune responses, including antibody homogeneity and IgG subclass distribution, were analyzed.

Main Results:

• Alum-adjuvanted vaccines conferred partial protection against monkeypox virus challenge.
• The addition of CpG adjuvant to the subunit vaccine resulted in full protection.
• CpG-adjuvanted vaccine elicited a more homogeneous antibody response and stronger IgG1 levels.
• Protection was associated with robust cellular and humoral immune responses.

Conclusions:

• A subunit vaccine incorporating vaccinia virus membrane proteins and CpG adjuvant is highly effective against orthopoxvirus infection.
• CpG adjuvant significantly enhances the protective efficacy of the subunit vaccine.
• This novel subunit vaccine represents a safer and potent alternative to live vaccinia virus vaccines for smallpox and orthopoxvirus prevention.