Reflections on early malaria vaccine studies, the first successful human malaria vaccination, and beyond

Abstract

Advances towards protective vaccines against malaria were made feasible by the development of a rodent model of mammalian malaria that allowed production of all stages of the malaria parasite for study. Investigations with sporozoites (the stage transmitted by mosquitoes in their saliva) demonstrated that immunization with radiation-attenuated sporozoites could produce a solid, sterile immunity, first shown in studies with mice and later with human volunteers. Protective immune mechanisms involve anti-sporozoite antibodies that immobilize sporozoites injected into the skin by mosquitoes, followed by CD4+ and CD8+ T-cells acting against liver stage parasites produced by sporozoites that have escaped antibody-based immunity and invaded hepatocytes. Two alternative approaches now being used in human trials are immunization with intact, attenuated sporozoites vs. immunization with "sub-unit" vaccines based on immunogenic components of sporozoites or liver stage parasites. In addition to immunization against these pre-erythrocytic stages, encouraging progress is being made on immunization against blood stage parasites and on immunization for production of transmission-blocking antibodies. There is reason to be optimistic that one or more of the approaches will work on a large scale, and that a multi-stage vaccine may be able to combine several of these approaches in a sequential immunological assault against the malaria parasite as it progresses through its stages.

Malaria Parasite-Synthesized Heme Is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection

“…Irradiated sporozoites serve as a malaria vaccine candidate [4]. There are several current efforts to design and stabilize irradiated sporozoites for large-scale clinical trials [34]–[36].…”

“…Sporadic resistance is also seen in P. vivax [1]. Emerging resistance to the artemisinin-based combination therapies [2] and the absence of an effective vaccine highlight an urgent need to develop new drug targets and vaccine candidates [3], [4]. The de novo heme-biosynthetic pathway of the malaria parasite offers potential drug targets and new vaccine candidates.…”

The Extraordinary Evolutionary History of the Reticuloendotheliosis Viruses

“…In 1935, Émile Brumpt of the Pasteur Institute had identified Plasmodium gallinaceum , a parasite causing malarial disease in poultry, during an excursion to Ceylon (now Sri Lanka) [45]. However, P. gallinaceum could not be introduced to the United States due to strict quarantine regulations against importation of poultry pathogens [46]. Reasoning that other avian species from the same geographic region might harbor a similar parasite, Coggeshall screened some South East Asian bird species that had been introduced to the New York Zoological Park in the 1920s by ornithologist Lee Saunders Crandall [47].…”

Arrested Plasmodium liver stages as experimental anti-malaria vaccines

“…Complementary vaccine approaches aim at targeting the pathogenic blood stages and transmission stages. review review intravenous injection of radiation-attenuated sporozoites (γ-spz or RAS) in mice [24][25][26][27][28][29][30] (Fig. 1).…”