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

Elife. 2018 Jun 19:7:e35213. doi: 10.7554/eLife.35213.

Abstract

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.

Keywords: Anopheles stephensi; Plasmodium berghei; epidemiology; global health; infectious disease; microbiology; mouse; multigenerational population assay; pre-erythrocytic vaccine; synergy; transmission-blocking vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / parasitology
  • Antibodies, Blocking / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Protozoan / administration & dosage*
  • Drug Synergism
  • Female
  • Humans
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control*
  • Malaria Vaccines / administration & dosage*
  • Mice
  • Mosquito Vectors / parasitology
  • Parasite Load
  • Plasmodium berghei / drug effects
  • Plasmodium berghei / immunology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Salivary Glands / parasitology
  • Sporozoites / chemistry
  • Sporozoites / immunology*
  • Trophozoites / chemistry
  • Trophozoites / immunology

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Protozoan
  • Malaria Vaccines
  • Pfs25 protein, Plasmodium falciparum
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan