First evaluation in humans of a chemically attenuated p. Falciparum whole parasite blood-stage vaccine (#77)
Malaria is a leading cause of morbidity and mortality attributable to infectious disease. The possibility of a malaria vaccine was first realized in the 1940s, yet a vaccine capable of inducing long-lasting immunity remains elusive. We have shown that a chemically attenuated whole parasite blood-stage vaccine, consisting of ring-stage malaria parasites attenuated with the cyclopropylpyrroloindole analogue Tafuramycin-A (TF-A), offers profound CD4 T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models. A clinical-grade P. falciparum 7G8 cell bank was used to manufacture and evaluate this vaccine approach in humans. Malaria-naïve volunteers were inoculated with a single dose of 3 x 107P. falciparum 7G8 parasitised erythrocytes treated with TF-A, to evaluate the safety and immunogenicity of chemically attenuated P. falciparum blood-stage parasites in humans. They were injected with either ring-stage parasites (n=8) or purified trophozoite-stage parasites (n=3). Parasite-specific antibody and T cell responses were measured. The inoculum was well tolerated. Species and strain transcending CD4 and CD8 Plasmodium-specific T cell responses were induced in recipients whereas Plasmodium-specific IgG was not detected. Production of IFN-γ and TNF was also observed. These studies demonstrate that a chemically attenuated whole parasite P. falciparum blood-stage vaccine can induce Plasmodium-specific T cell responses in malaria-naïve volunteers. These data support evaluating the efficacy of this vaccine approach in humans.