Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

Das, Sreedam Chandra; Price, John F.; Gosling, Katharine M.; MacLennan, Nicola; Ataíde, Ricardo; Irani, Vashti; Atmosukarto, Ines I.; Anders, Robin F.; Richards, Jack S.; MacRaild, Christopher A.; Norton, Raymond S.

doi:10.1016/j.vaccine.2021.02.010

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…In another study, the engraftment of MSP2 proteins obtained from P. falciparum with liposomes and supplemented with TLR4/2 antigen resulted in a strong immune response in a murine model. Briefly, immunization of mice with this MSP2 vaccine formulation generated a protective antibody response against conserved C-terminal domains of MSP2 ( 133 ). Among MSPs, the MSP3 antigen has been reported as a highly immunogenic vaccine candidate which can induce protective immune responses.…”

Section: Vaccine Candidates Against Plasmodiummentioning

confidence: 99%

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

et al. 2023

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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.

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Section: Vaccine Candidates Against Plasmodiummentioning

confidence: 99%

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

et al. 2023

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Pathogenesis of Plasmodium falciparum

Noor

2024

Drug Targets for Plasmodium Falciparum: Historic to Future Perspectives

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Naturally acquired IgG responses to Plasmodium falciparum do not target the conserved termini of the malaria vaccine candidate Merozoite Surface Protein 2

Zerebinski,

Margerie,

Han

et al. 2024

Front. Immunol.

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IntroductionMalaria remains a significant burden, and a fully protective vaccine against Plasmodium falciparum is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen Merozoite Surface Protein 2 (MSP2) are associated with protection from P. falciparum malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to study the genetic diversity and immune responses towards antigens from clinical isolates with unprecedented detail. This study sought to better understand naturally acquired MSP2-specific antibody responses.MethodsIgG responses against recombinantly expressed full-length, central polymorphic regions, and peptides derived from the conserved termini of MSP2 variants sequenced from patient isolates, were tested in plasma from travelers with recent, acute malaria and from individuals living in an endemic area of Tanzania.ResultsIgG responses towards full MSP2 and truncated MSP2 antigens were variant specific. IgG antibodies in the plasma of first-time infected or previously exposed travelers did not recognize the conserved termini of expressed MSP2 variants by ELISA, but they bound 13-amino acid long linear epitopes from the termini in a custom-made peptide array. Alphafold3 modelling suggests extensive structural heterogeneity in the conserved termini upon antigen oligomerization. IgG from individuals living in an endemic region, many who were asymptomatically infected, did not recognize the conserved termini by ELISA.DiscussionOur results suggest that responses to the variable regions are critical for the development of naturally acquired immunity towards MSP2.

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Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

Cited by 3 publications

References 51 publications

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Pathogenesis of Plasmodium falciparum

Naturally acquired IgG responses to Plasmodium falciparum do not target the conserved termini of the malaria vaccine candidate Merozoite Surface Protein 2

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