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 major global health threat, with current vaccines offering limited efficacy.
• Existing subunit vaccines target pre-erythrocytic stages but fail to induce durable T cell immunity.
• Whole-organism vaccines provide sterilizing protection but face challenges in administration and production.

Approach:

• Developed an accelerated prime-and-trap vaccination regimen using self-replicating RNA encoding P. yoelii circumsporozoite protein (CS) delivered via LION™ nanocarrier.
• Combined RNA priming with whole-organism radiation-attenuated sporozoites (RAS) as a trapping dose.
• Utilized a P. yoelii mouse model to evaluate the efficacy of this novel accelerated regimen.

Key Points:

• The prime-and-trap strategy elicits both high antibody titers and liver-resident memory CD8+ T cells (Trm).
• This approach aims to overcome limitations of current malaria vaccines, enhancing both efficacy and long-term protection.
• The regimen demonstrated sterile protection against malaria in the P. yoelii mouse model.

Conclusions:

• The accelerated prime-and-trap vaccination regimen offers a promising new approach to malaria vaccine development.
• This strategy presents a viable path for dose-sparing, same-day malaria vaccines.
• Further preclinical and clinical testing is warranted to translate these findings into human application.