Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in...

Area of Science:

• Immunology
• Vaccinology
• Parasitology

Background:

• Malaria transmission-blocking vaccine candidates targeting Pfs25 and Pfs230 antigens have progressed to clinical trials.
• Previous studies showed Exoprotein A (EPA) conjugates elicited functional immunity in humans but with limited durability.
• Non-human primates better model human immune responses to these malaria vaccine candidates than mice.

Purpose of the Study:

• To evaluate the efficacy of a novel liposomal adjuvant, ALFQ (TLR4 agonist and QS21), in enhancing the immunogenicity of Pfs25-EPA and Pfs230D1-EPA malaria vaccine candidates.
• To assess the durability of functional activity induced by these conjugates in Rhesus macaques.

Main Methods:

• Rhesus macaques were vaccinated with Pfs25-EPA and Pfs230D1-EPA conjugates formulated with the ALFQ adjuvant.
• Immunogenicity was assessed by measuring antibody responses, avidity, and IgG subclass levels.
• Functional activity was evaluated through standard malaria transmission-blocking assays.

Main Results:

• Two vaccinations with both conjugates induced strong antibody responses and functional activity, which declined rapidly.
• A third vaccination of Pfs230D1-EPA with ALFQ resulted in functional activity lasting at least 9 months.
• Antibody avidity increased with vaccination and strongly correlated with functional activity; Th1/Th2 IgG subclasses also correlated with activity.

Conclusions:

• The ALFQ adjuvant enhances the immunogenicity and functional activity of Pfs25-EPA and Pfs230D1-EPA malaria vaccine candidates in Rhesus macaques.
• A third dose of Pfs230D1-EPA is crucial for achieving durable functional immunity.
• Antibody avidity and IgG subclass profiles are key indicators of vaccine efficacy for malaria transmission-blocking vaccines.