Evaluation of two lead malaria transmission blocking vaccine candidate antibodies in natural parasite-vector combinations

Abstract

Transmission blocking vaccines (TBV) which aim to control malaria by inhibiting human-to-mosquito transmission show considerable promise though their utility against naturally circulating parasites remains unknown. The efficacy of two lead candidates targeting Pfs25 and Pfs230 antigens to prevent onwards transmission of naturally occurring parasites to a local mosquito strain is assessed using direct membrane feeding assays and murine antibodies in Burkina Faso. The transmission blocking activity of both candidates depends on the level of parasite exposure (as assessed by the mean number of oocysts in control mosquitoes) and antibody titers. A mathematical framework is devised to allow the efficacy of different candidates to be directly compared and determine the minimal antibody titers required to halt transmission in different settings. The increased efficacy with diminishing parasite exposure indicates that the efficacy of vaccines targeting either Pfs25 or Pfs230 may increase as malaria transmission declines. This has important implications for late-stage candidate selection and assessing how they can support the drive for malaria elimination.

High Plasmodium infection intensity in naturally infected malaria vectors in Africa

“…Results of standard and direct membrane feeding assays (SMFA and DMFA, respectively) are often challenged because the parasite exposure generated is seen as artificially high compared to natural parasite exposure(24). However, the parasite exposure we observed in high transmission area falls into a similar range as recent SMFA studies(18,41,42). Transmission-blocking interventions that show a dose-response to parasite exposure, such as transmission-blocking vaccines, might initially show lower efficacy when deployed in high-transmission areas.…”

“…Variation in host natural immunity between locations could also affect this relationship so more data in various epidemiological settings would be needed to corroborate the relationship. If confirmed, a human Plasmodium prevalence-mosquito natural parasite exposure curve could help predict initial and long-term TBV efficacy before clinical trial or deployment, as well as the minimum antibody titer necessary to achieve blockade(18). The World Health Organization has recently stressed the need to target control in high burden countries such as Burkina Faso(43).…”

“…Vaccines which interrupt malaria parasite transmission by targeting sexual and sporogonic stages of the parasite are referred to as transmission-blocking vaccines. The efficacy of these vaccine candidates in reducing the number of infected mosquitoes shows a dose response to parasite exposure(16–18) which depends primarily on the number of mature gametocytes in the blood, though many other factors are known to contribute. These include gametocyte maturity, parasite clone diversity, host blood component and environmental conditions (18–23).…”

“…The efficacy of these vaccine candidates in reducing the number of infected mosquitoes shows a dose response to parasite exposure(16–18) which depends primarily on the number of mature gametocytes in the blood, though many other factors are known to contribute. These include gametocyte maturity, parasite clone diversity, host blood component and environmental conditions (18–23). Parasite exposure therefore represents the realised infectiousness of a human host assuming that the mosquito survives long enough for all oocysts to develop.…”

Detection of Plasmodium berghei infected Anopheles stephensi using near-infrared spectroscopy

“…There is increasing interest in quantifying the number/density of parasites in a mosquito and not just whether it is infected or not. Evidence indicates that highly infected mosquitoes are more infectious [10], and that parasite intensity might influence the efficacy of transmission blocking and pre-erythrocytic vaccines [10,11].…”