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Order Martellivirales: Togaviridae
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The circumsporozoite protein (CSP) of the Plasmodium falciparum malaria parasite was used as a foreign antigen. The central NANP repeat region of CSP was chosen as the epitope to be exposed, since it was characterized as the major surface antigen displayed during the infective stage of malaria. In fact, the epitope was highly conserved among different strains of P. falciparum and was considered an immunodominant B cell epitope (Crompton et al. 2010). The five NANP repeats, namely the stretch GNP(NANP)5NAG, was inserted into the cloning sites of the αVLP (αVLP-NANP) and E3αVLP(E3αVLP-NANP) genes. The Dual-NANP carried the NANP repeat epitope in both insertion sites, thus displaying 480 copies of the five NANP repeats per each VLP.
Vectorial Capacity
Published in Jacques Derek Charlwood, The Ecology of Malaria Vectors, 2019
The method most widely used today is the ELISA technique developed by Wirtz and Burkot. In the ELISA Plasmodium, circumsporozoite protein (CSP) acts as the antigen. Mosquitoes are ground up (either in pools or individually) in phosphate buffered saline (PBS) and added to ELISA plates that are treated with antibodies to the protein. On incubation, the CSP binds to the antibody. A further antibody that turns blue when a peroxidase is added is also incubated and a colour change produced in positive wells. The process is shown in Figure 7.26.
Rationale and technique of malaria control
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
David A Warrell, Herbert M Gilles
Pre-erythrocytic stage vaccines are designed to prevent the parasite’s infective sporozoite stage from entering or developing within the liver cells. This would prevent infection in non-immunes. Four vaccines based on the circumsporozoite protein are in various stages of studies and trials in Africa, the USA and Europe.
Preclinical advances and the immunophysiology of a new therapeutic Chagas disease vaccine
Published in Expert Review of Vaccines, 2022
Kathryn M. Jones, Cristina Poveda, Leroy Versteeg, Maria Elena Bottazzi, Peter J. Hotez
Over 100 years of research has been dedicated to developing vaccines to prevent or treat Chagas disease, yet no vaccine has achieved licensure for human use to date. However, recent advancements predict that vaccines against parasitic diseases, and Chagas disease specifically, will become a reality imminently. In 2021, the World Health Organization recommended the use of the RTS,S/ASO1 malaria vaccine in children in sub-Saharan Africa [232]. The RTS,S/ASO1 vaccine comprised a fusion recombinant protein containing Plasmodium falciparum circumsporozoite protein (CSP) antigen and the GlaxoSmithKline ASO1 adjuvant system, consisting of the TLR4 agonist monophosphoryl lipid A (MPL), liposomes, and the saponin QS-21 [233]. This advancement shows the feasibility of utilizing antiparasitic vaccines as a public health tool to reduce global burdens of disease and providing a framework for widespread implementation of such a vaccine with existing infection control tools. Ultimately, this work is paving the way for use of vaccines against other parasitic diseases such as Chagas disease.
Structural vaccinology of malaria transmission-blocking vaccines
Published in Expert Review of Vaccines, 2021
Malaria vaccine development has been hindered by the complexity of the multi-stage parasite life cycle, as well as an incomplete understanding of host-pathogen interactions that should be targeted for effective vaccination [1]. RTS,S/AS01, the most clinically advanced malaria vaccine, is based on the parasite circumsporozoite protein (CSP) [1,2]. RTS,S/AS01 has been shown to significantly reduce malaria and life-threatening severe malaria in young African children, although its partial efficacy and longevity are suboptimal [1]. Many other potential vaccines currently in development can be broadly categorized as (1) pre-erythrocytic vaccines that aim to prevent infection such as RTS,S/AS01, (2) asexual blood stage vaccines that aim to prevent clinical manifestations of disease, and (3) sexual stage vaccines that aim to prevent parasite transmission by the mosquito host [3].
Human challenge models: tools to accelerate the development of malaria vaccines
Published in Expert Review of Vaccines, 2019
Martha M. Cooper, Claire Loiseau, James S. McCarthy, Denise L. Doolan
Plasmodium species parasites are genetically diverse [61] (a substantial focus of the MalariaGen project [62]). Since leading vaccine candidates are mostly based on polymorphic antigens with the vaccine target representing only a single variant strain, and immunity to malaria is often strain-specific [4], this represents a fundamental challenge to the development of an effective vaccine [63,64]. Indeed, the suboptimal efficacy of the most advanced malaria vaccine candidate MosquirixTM/RTS,S has been associated with genetic diversity of the target circumsporozoite protein (CSP) [65,66]. The P. falciparum strains used in CHMI have to date been almost exclusively 3D7 (or its parental strain NF54). These strains have been continuously cultured in the laboratory for over 30 years [31] and are very well characterised; indeed, 3D7 is the basis of the genome, transcriptome and proteome of P. falciparum [67–69] and most vaccine candidates [19,70–73]. However, the 3D7 strain is often not the most prevalent strain in malaria-endemic areas. Evidence of strain-transcending immunity has been reported in some studies [74], indicating that cross-strain protection may be achieved. The ability to test candidate vaccines against different strains in CHMI would be an informative and ideally a critical step in the vaccine development pipeline, enabling candidates that induce a level of strain-transcending immunity to be prioritised for development.