Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Abstract

Malaria is a global infectious disease that remains a leading cause of morbidity and mortality in the developing world. Multiple environmental and host and parasite factors govern the clinical outcomes of malaria. The host immune response against the Plasmodium parasite is heterogenous and stage-specific both in the human host and mosquito vector. The Plasmodium parasite virulence is predominantly associated with its ability to evade the host’s immune response. Despite the availability of drug-based therapies, Plasmodium parasites can acquire drug resistance due to high antigenic variations and allelic polymorphisms. The lack of licensed vaccines against Plasmodium infection necessitates the development of effective, safe and successful therapeutics. To design an effective vaccine, it is important to study the immune evasion strategies and stage-specific Plasmodium proteins, which are targets of the host immune response. This review provides an overview of the host immune defense mechanisms and parasite immune evasion strategies during Plasmodium infection. Furthermore, we also summarize and discuss the current progress in various anti-malarial vaccine approaches, along with antibody-based therapy involving monoclonal antibodies, and research advancements in host-directed therapy, which can together open new avenues for developing novel immunotherapies against malaria infection and transmission.

A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites

“…The human mAb, CIS43LS, which targets PfCSP, protected human volunteers against challenge with P. falciparum when administered subcutaneously at low doses 54 . Although the major focus of current immunotherapy studies has been the sporozoite antigen CSP, if one aim is to reduce morbidity and mortality, immunotherapy with antibodies targeting asexual blood-stage antigens should be considered as a complement to chemotherapy 55 . AMA1 is an attractive candidate for this approach as it is expressed in both asexual and sexual stages of the parasite life cycle.…”

State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis

“…Indeed, a better biological profile was exhibited by the indole isosteres 1b and 1c , for which a superior SI was noted (Table 1 ). In the following step, the indole diamidines were tested in vivo using a mouse model which recapitulated the acute hemolymphatic phase of African trypanosomiasis; interestingly, the 2-[ 5 -(furan-2-yl)thiophen-2-yl]indole derivative ( 1c ) demonstrated to cure all T.b.r. infected mice at a dose minor than that of pentamidine.…”

“…RTS, S/AS01 (Mosquirix™) is the first licensed malaria vaccine for P. falciparum to be widely recommended by WHO for children at risk; a two years immunization pilot program in Ghana, Kenya, and Malawi [ 3 ] has given positive results in terms of safety and efficacy, lowering the disease severity and the hospitalization rate of pediatric population with malaria infection. However, some concerns have arisen due to the short life time of immunity induced by the vaccine as well as the high production costs [ 4 , 5 ]. Another vaccine candidate (R21/Matrix-M) has entered a phase 3 clinical trial ( ClinicalTrials.gov Identifier: NCT04704830), and if it is approved, it would be an additional resource for the global supply.…”

Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies

“…However, in the current scenario of increased emergence of multidrug resistance, interest in developing mAbs for therapeutic applications is rapidly gaining momentum. Currently, mAbs are the fastest-growing category of therapeutics entering clinical studies worldwide and have shown promise against HIV, influenza, malaria, Ebola, and SARS-CoV-2 ( 2 , 3 ). Particularly, mAbs have shown remarkable promise in the management of solid tumors and in the use of immunotherapy to treat a broad range of cancers, including lymphomas and breast, cervical, and gastric cancers, among others.…”