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

• Published in: eLife Vol. 7
• Main Authors: Sherrard-Smith, Ellie, Sala, Katarzyna A, Betancourt, Michael, Upton, Leanna M, Angrisano, Fiona, Morin, Merribeth J, Ghani, Azra C, Churcher, Thomas S, Blagborough, Andrew M
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications, Ltd 19.06.2018; eLife Sciences Publications Ltd
• Subjects: Animals; Anopheles - parasitology; Anopheles stephensi; Antibodies, Blocking - administration & dosage; Antibodies, Monoclonal - administration & dosage; Antibodies, Protozoan - administration & dosage; Drug Synergism; Epidemiology and Global Health; Female; Humans; Malaria - immunology; Malaria - parasitology; Malaria - prevention & control; Malaria Vaccines - administration & dosage; Mice; Microbiology and Infectious Disease; Mosquito Vectors - parasitology; multigenerational population assay; Parasite Load; Plasmodium berghei; Plasmodium berghei - drug effects; Plasmodium berghei - immunology; pre-erythrocytic vaccine; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Salivary Glands - parasitology; Sporozoites - chemistry; Sporozoites - immunology; synergy; transmission-blocking vaccine; Trophozoites - chemistry; Trophozoites - immunology; global health; epidemiology; mouse; Anopheles stephensi; Plasmodium berghei; pre-erythrocytic vaccine; synergy; infectious disease; multigenerational population assay; microbiology; transmission-blocking vaccine
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.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 to 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.