HYBRID EVENT: You can participate in person at Paris, France or Virtually from your home or work.

6th Edition of World Congress on Infectious Diseases

June 24-26, 2024 | Paris, France

June 24 -26, 2024 | Paris, France
Infection 2024

Cristina Meehan

Speaker at Infectious Diseases Conferences - Cristina Meehan
National Institutes of Health, NIAID, United States
Title : The next frontier in malaria prevention: Pfs230D1 transmission-blocking vaccine’s novel surrogate assay of efficacy


In 2023, malaria impacted 247 million individuals across 85 countries, resulting in 619,000 global deaths. The international focus to develop a higher efficacy malaria vaccine is a top priority, yet the complex parasite lifecycle poses a significant challenge to vaccine development. With the urgent call for cutting-edge vaccine strategies, innovative approaches such as transmission-blocking vaccines (TBV) have garnered considerable attention. Pfs230D1 (the leading TBV) specifically targets parasite gamete surface proteins in the mosquito midgut, preventing gamete fusion by complement-dependent lysis, thus inhibiting further transmission of malaria from mosquito to human in the community. As Pfs230D1 advances to Phase 3 clinical trials, a growing need for pioneering assays capable of measuring functional antibody responses and predicting vaccine efficacy is paramount.

Thus here, we utilized human monoclonal antibodies from Mali volunteers who received Pfs230D1-EPA to establish a novel competitive ELISA (CE) measuring functional antibody responses (FAR). Analysis of 186 serum samples from NCT02942277 demonstrated the CE assay's ability to characterize FAR and identifying the most efficacious dosing regimen. Total IgG CE analysis showed higher FAR in the full dose arm (546.3 ± 427.8 units) than the fractional dose arm (258.4 ± 212.1, p<0.001). IgG1 CE analysis displayed higher FAR in the full dose arm (51.1 ± 17.2) compared to the fractional dose arm (44.2 ± 20.8, p=0.1139). Correlation of CE assays to pre-existing mosquito assays revealed positive correlations (0.63 for IgG1 and 0.44 for total IgG), demonstrating the potential for these assays to serve as surrogate measures of vaccine efficacy. Furthermore, linear regression of total IgG responses suggested that a one-unit increase in FAR content increased the odds of blocking transmission by 0.006. These findings lay the groundwork for standardized assays to evaluate vaccine efficacy and durability (including IgG isotypes and complement specific FAR) during Phase 3 clinical trials.


Will be Updated Soon...