Poster Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

A controlled infection immunisation (CII) strategy for a malaria vaccine   (#104)

Reshma J. Nevagi 1 , Tanjir Islam 2 , Emily Cooper 1 , Geoff Birrell 3 , Mariusz Skwarczynski 2 , Istvan Toth 2 4 5 , Danielle I. Stanisic 1 , Michael F. Good 1
  1. Institute for Glycomics, Griffith University, Southport, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia Campus, Brisbane, QLD, Australia
  3. Australian Defence Force Malaria & Infectious Disease Institute, Enoggera, QLD, Australia
  4. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
  5. Institute for Molecular Bioscience, The University of Queensland, St Lucia Campus, Brisbane, QLD, Australia

In 2020, there were 241 million malaria cases and 627,000 malaria-associated deaths [1]. Historically, malaria vaccine research has focused on parasite-derived recombinant proteins. When tested in field studies, these sub-unit vaccines, have shown limited efficacy due to antigenic polymorphism and the genetic diversity of malaria parasites. The approved sub-unit vaccine, MosquirixTM, has only moderate efficacy (<40%) with a limited duration of protection [2]. Therefore, a more effective vaccine is required.

We are developing a whole parasite vaccine strategy, Controlled Infection Immunisation (CII). This involves injecting infectious blood-stage malaria parasites and curtailing the infection with an anti-malarial drug while parasite levels are low and not harmful. CII allows exposure of the immune system to a broad repertoire of parasite antigens, thus enabling induction of protective immunity. Previous CII studies have administered the anti-malarial drug after a delayed period and as a multi-dose regimen [3]. For CII to be a safe vaccination approach, the anti-malarial drug should be administered on the same day as the parasites and as a single dose. Therefore, we are focused on developing novel anti-malarial drug formulations to enable single-dose drug administration.  The formulation must allow the drug to persist at parasiticidal concentrations until all parasites are killed and avoid peak-related toxicity.

A novel anti-malarial drug formulation has been optimised and exhibited sustained-release (SR) kinetics in vitro. Examination of in vivo drug release kinetics in mice showed a lower peak plasma concentration when compared with the standard anti-malarial drug formulation. When this novel SR formulation was evaluated in the context of CII with the rodent parasite, P. yoelii YM, parasitemias were not as well controlled as those in mice that received CII with the standard formulation. Future studies will evaluate tissue distribution profile of the anti-malarial drug to inform optimisation of this SR formulation to maximise parasite control.

  1. World Health Organisation, World Malaria Report, 2021.
  2. M.B. Laurens, RTS,S/AS01 vaccine (Mosquirix™): an overview, Human Vaccines & Immunotherapeutics, 2020, 16(3), 480-489.
  3. D. J. Pombo, G. Lawrence, C. Hirunpetcharat, C. Rzepczyk, M. Bryden, N. Cloonan et al. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. The Lancet. 2002, 360, 610-617.