First evaluation in humans of a chemically attenuated <em>p. Falciparum</em> whole parasite blood-stage vaccine — ASN Events

First evaluation in humans of a chemically attenuated p. Falciparum whole parasite blood-stage vaccine (#77)

Danielle I Stanisic 1 , James Fink 2 , Xue Liu 1 , Sarah Coghill 2 , Lana Sundac 2 , Johanna Mayer 2 , Letitia Gore 2 , Ingrid Rodriguez 1 , Jolien Pingnet 1 , Nicole Willemsen 1 , Sai De 1 , Jessica Powell 1 , Moses Lee 3 , John Gerrard 2 , Michael F Good 1
  1. Griffith University, Gold Coast Campus, Southport, QLD, Australia
  2. Gold Coast University Hospital, Southport, QLD, Australia
  3. Georgia State University, Georgia, USA

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.

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