Th1 immune response to <i>Plasmodium falciparum</i> recombinant thrombospondin‐related adhesive protein (TRAP) antigen is enhanced by TLR3‐specific adjuvant, poly(I:C) in <scp>BALB</scp>/c mice

Mehrizi, Akram Abouie; Torzani, M. Ameri; Zakeri, Sedigheh; Zadeh, A. Jafary; Babaeekhou, Laleh

doi:10.1111/pim.12538

Cited by 10 publications

(3 citation statements)

References 95 publications

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“…There were statistically significant differences regarding cytokines in the 50-peptide mixture, specifically for IL-2 ( p = 0.0132), but p -values were not significant for IFN-γ ( p = 0.7521), TNF ( p = 0.3659), IL-6 ( p = 0.6502), IL-5( p = 0.3512), or IL-4 ( p = 0.4553). This data clearly suggested T-cell stimulation in proliferation assays and a Th1 subset activating Ab production ( Figure 12 ) ( 66 , 67 ).…”

Section: Resultsmentioning

confidence: 72%

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

Patarroyo

Pabón

et al. 2022

Front. Immunol.

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Fifty ~20–amino acid (aa)–long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus’ main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing β-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRβ1* (HLA-DRβ1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRβ1* molecules), predicted to cover 77.5% to 83.1% of the world’s population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

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Section: Resultsmentioning

confidence: 72%

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

Patarroyo

Pabón

et al. 2022

Front. Immunol.

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“…In one study, BALB/c mice were immunized with recombinant P. falciparum TRAP ( Pf TRAP) along with poly (I:C) adjuvant. Vaccination with Pf TRAP induced Th1 immune response and high titers of protective IgG antibodies ( 109 ). In another study, a vaccine formulation was prepared by fusion of P. berghei CSP and TRAP antigen along with Addavax adjuvant.…”

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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“…Thus, the different patterns in the immunological response generated by the effect of the adjuvants could directly influence the protective effect of each formulation, mainly because they have different mechanisms of action ( 10 ). Poly (I:C) is a synthetic double-stranded RNA (dsRNA) designed to act like a natural ligand of TLR3 receptor, and known to elicit long-lived antibodies with strong Th1 responses against P. falciparum antigen ( 11 ). On the other hand, Montanide ISA 720 is an oil-based emulsion dispersion that activates innate inflammatory responses and recruits antigen-presenting cells (APCs), enhancing the persistency of the antigen at the injection site, which favors the antigen delivery to immune cells but could also cause high reactogenicity ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720

et al. 2022

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Adjuvants are essential for vaccine development, especially subunit-based vaccines such as those containing recombinant proteins. Increasing the knowledge of the immune response mechanisms generated by adjuvants should facilitate the formulation of vaccines in the future. The present work describes the immune phenotypes induced by Poly (I:C) and Montanide ISA 720 in the context of mice immunization with a recombinant protein based on the Plasmodium vivax circumsporozoite protein (PvCSP) sequence. Mice immunized with the recombinant protein plus Montanide ISA 720 showed an overall more robust humoral response, inducing antibodies with greater avidity to the antigen. A general trend for mixed Th1/Th2 inflammatory cytokine profile was increased in Montanide-adjuvanted mice, while a balanced profile was observed in Poly (I:C)-adjuvanted mice. Montanide ISA 720 induced a gene signature in B lymphocytes characteristic of heme biosynthesis, suggesting increased differentiation to Plasma Cells. On the other hand, Poly (I:C) provoked more perturbations in T cell transcriptome. These results extend the understanding of the modulation of specific immune responses induced by different classes of adjuvants, and could support the optimization of subunit-based vaccines.

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Th1 immune response to Plasmodium falciparum recombinant thrombospondin‐related adhesive protein (TRAP) antigen is enhanced by TLR3‐specific adjuvant, poly(I:C) in BALB/c mice

Cited by 10 publications

References 95 publications

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World’s Population

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720

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