Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Malaria remains a significant global health threat, with current subunit vaccines (RTS,S, R21) lacking robust CD8+ T-cell responses for long-term protection.
• Whole-organism vaccines (RAS) provide sterile protection but have limitations including burdensome production and multiple administration requirements.

Purpose of the Study:

• To develop an accelerated vaccination regimen combining self-replicating RNA and whole-organism vaccines to induce both humoral and T-cell responses for malaria protection.
• To evaluate the efficacy of a prime-and-trap strategy using a novel nanocarrier delivery system.

Main Methods:

• Developed a prime-and-trap strategy using self-replicating RNA encoding P. yoelii circumsporozoite (CS) protein delivered via LION™ nanocarrier, followed by whole-organism radiation-attenuated sporozoites (RAS).
• Administered the vaccine regimen in accelerated schedules (5-day or same-day) to mice.
• Assessed immune responses and protection against Plasmodium sporozoite challenge at different time points.

Main Results:

• The accelerated regimen, particularly the same-day immunization, induced strong immune responses.
• Same-day immunization in mice delayed blood patency by 2 days and achieved 90% sterile protection against a 3-week sporozoite challenge.
• Durable 70% sterile protection was observed against a 2-month sporozoite challenge with the same-day regimen.

Conclusions:

• The prime-and-trap strategy with an accelerated, dose-sparing regimen offers a promising approach for developing effective malaria vaccines.
• This approach maintains protective immunity via antibodies and T-cell responses, potentially overcoming limitations of current vaccine candidates.
• The findings support progression to late-stage preclinical and clinical testing for a novel malaria vaccine strategy.