Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis

Al-Nazal, Hanan A; Cooper, Emily; Ho, Mei‐Fong; Eskandari, Sharareh; Majam, Victoria; Giddam, Ashwini Kumar; Hussein, Waleed M.; Islam, Tanjir; Skwarczynski, Mariusz; Tóth, István; Kumar, Sanjai; Zaid, Ali; Batzloff, Michael R.; Stanisic, Danielle I.; Good, Michael F.

doi:10.1016/j.chom.2021.04.008

Cited by 18 publications

(17 citation statements)

References 45 publications

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“…Importantly, the ability of M2 anchored into liposomes to greatly enhance humoral immune responses against a bacterial antigen has also been proven (unpublished data). Along the same line, we also demonstrated that the mannose–lipid conjugate M3 easily anchored into liposomes induced cellular immunity against malaria and babesia parasites [ 31 , 47 , 48 , 49 ]. Finally, we had also previously proven that the lapidated-cell-penetrating peptide KALA ( CPP ), upon anchoring to liposomes, triggered the production of opsonic antibodies against a co-anchored peptide antigen [ 32 ].…”

Section: Resultsmentioning

confidence: 61%

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

et al. 2023

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Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.

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Section: Resultsmentioning

confidence: 61%

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

et al. 2023

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“…In a B. microti murine model, intact RBC cellular membrane was shown to play an essential role in parasite-antigen-presenting cell (APC) interactions in the spleen and liver [ 33 ]. The efficacy of vaccines based on organisms contained within liposomal membranes, mimicking the structure of pRBCs, was demonstrated in a mouse model of malaria [ 34 ].…”

Section: Advances In B Microti Vaccine Developmentmentioning

confidence: 99%

“…Moreover, vaccination protected splenectomised mice, which suggests that it might be effective in asplenic individuals, one of the target groups of the future vaccine. Interestingly, vaccine-induced protection seemed to be dependent of CD4+ T cells and macrophage, with B cells and antiparasite antibodies showing little contribution [ 33 ]. Still, CD4+ T cells and macrophage-mediated response is insufficient to induce effective immunity; therefore, antibodies production stimulation is the most commonly proposed strategy for future vaccine development.…”

Section: Advances In B Microti Vaccine Developmentmentioning

confidence: 99%

Advances in Babesia Vaccine Development: An Overview

et al. 2023

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Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. Since the current preventive measures against babesiosis are insufficient, there is increasing pressure to develop a vaccine. In this review, we survey the achievements and recent advances in the creation of antibabesiosis vaccine. The scope of this review includes the development of a vaccine against B. microti, B. bovis, B. bigemina, B. orientalis and B. divergens. Here, we present different strategies in their progress and evaluation. Scientists worldwide are still trying to find new targets for a vaccine that would not only reduce symptoms among animals but also prevent the further spread of the disease. Molecular candidates for the production of a vaccine against various Babesia spp. are presented. Our study also describes the current prospects of vaccine evolution for successful Babesia parasites elimination.

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“…According to the results obtained with Bd37 and BmSA1 in two Babesia species, achieving a broad, multiplexed, serological assay might not be as difficult as expected. In addition to classic immunofluorescence assays using native antigens from in vitro cultures or infected animals, recombinant proteins have been successfully used in serological assays [68,69]. Some initial studies on B. divergens antigens have compared the immune response raised in different hosts and demonstrated a similar profile of recognized proteins [48].…”

Section: Use Of Major Babesia Antigens In the Management Of Human Babesiosis: Polymorphism And Cross-reactionsmentioning

confidence: 99%

Major Surface Antigens in Zoonotic Babesia

Delbecq

2022

Pathogens

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Human babesiosis results from a combination of tick tropism for humans, susceptibility of a host to sustain Babesia development, and contact with infected ticks. Climate modifications and increasing diagnostics have led to an expanded number of Babesia species responsible for human babesiosis, although, to date, most cases have been attributed to B. microti and B. divergens. These two species have been extensively studied, and in this review, we mostly focus on the antigens involved in host–parasite interactions. We present features of the major antigens, so-called Bd37 in B. divergens and BmSA1/GPI12 in B. microti, and highlight the roles of these antigens in both host cell invasion and immune response. A comparison of these antigens with the major antigens found in some other Apicomplexa species emphasizes the importance of glycosylphosphatidylinositol-anchored proteins in host–parasite relationships. GPI-anchor cleavage, which is a property of such antigens, leads to soluble and membrane-bound forms of these proteins, with potentially differential recognition by the host immune system. This mechanism is discussed as the structural basis for the protein-embedded immune escape mechanism. In conclusion, the potential consequences of such a mechanism on the management of both human and animal babesiosis is examined.

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Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis

Cited by 18 publications

References 45 publications

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

Advances in Babesia Vaccine Development: An Overview

Major Surface Antigens in Zoonotic Babesia

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