Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density

• Main Authors: Ellie Sherrard-Smith, Katarzyna A Sala, Michael Betancourt, Leanna M Upton, Fiona Angrisano, Merribeth J Morin, Azra C Ghani, Thomas S Churcher, Andrew M Blagborough
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2018-06-01
• Series: eLife
• Subjects: Anopheles stephensi; Plasmodium berghei; transmission-blocking vaccine; synergy; multigenerational population assay; pre-erythrocytic vaccine
• Online Access: https://elifesciences.org/articles/35213

Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7–94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1–87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts.