Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine...

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• A Plasmodium falciparum sporozoite (PfSPZ) vaccine has demonstrated safety in over 1500 individuals across various age groups and locations.
• Previous trials indicated lower vaccine efficacy (VE) of 20% in Tanzanian adults using a 5-dose regimen of 2.7 × 105 PfSPZ.
• Controlled Human Malaria Infection (CHMI) models are crucial for evaluating vaccine candidates against malaria.

Purpose of the Study:

• To optimize the dosage of PfSPZ Vaccine to enhance vaccine efficacy in Tanzania.
• To evaluate the impact of increased PfSPZ doses and reduced administration frequency on malaria vaccine effectiveness.

Main Methods:

• A double-blind, placebo-controlled trial was conducted in Tanzania.
• Participants received 3 doses of PfSPZ Vaccine at 8-week intervals, with doses adjusted to 9 × 105 or 1.8 × 106 PfSPZ.
• Vaccine efficacy was assessed via CHMI and by measuring time to parasitemia after controlled infection.

Main Results:

• The group receiving 9 × 105 PfSPZ achieved 100% vaccine efficacy against CHMI at 3 and 11 weeks post-vaccination.
• The group receiving 1.8 × 106 PfSPZ showed a significantly lower VE of 33% against CHMI.
• While antibody and T-cell responses were higher in the 1.8 × 106 PfSPZ group, the 9 × 105 PfSPZ dose demonstrated superior protection against malaria infection.

Conclusions:

• Increasing the PfSPZ Vaccine dose to 9 × 105 PfSPZ per dose significantly improved VE to 100% in Tanzanian adults.
• A higher dose of 1.8 × 106 PfSPZ per dose was associated with reduced vaccine efficacy, suggesting a potential dose-ceiling effect.
• Optimal dosing is critical for maximizing the effectiveness of the PfSPZ malaria vaccine in high-transmission areas.