<i>Plasmodium falciparum</i>
            Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies

Tripathi, Abhai K.; Oakley, Miranda S.; Verma, Nitin; Mlambo, Godfree; Zheng, Hong; Meredith, Scott; Essuman, Edward; Puri, Ankit; Skelton, Richard A.; Takeda, Kazuyo; Majam, Victoria; Quakyi, Isabella A.; Locke, Emily; Morin, Merribeth J.; Miura, Kazutoyo; Long, Carole A.; Kumar, Sanjai

doi:10.1126/scitranslmed.abg2112

Cited by 8 publications

(4 citation statements)

References 59 publications

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“…Both Pf 77 and Pf MDV-1 display less antigenic polymorphism and are known to induce naturally occurring antibodies in individuals living in endemic areas of Africa. These antigens are highly immunogenic and can induce transmission-reducing antibodies which may aid in the reduction of oocyst counts in Anopheles mosquito midgut ( 153 ).…”

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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“…MDV1 play a critical role in female gametocyte activation and accumulates in a few foci in the activated male gametocyte which are maintained until exflagellation. Additionally, Pf MDV1 generates naturally occurring antibodies in the adult population of Ghana, hinting that targeting these antigens could result in long-lasting immune responses (Tripathi et al 2021 ). Recently, researchers identified a new protein called microgamete surface protein (MiGS) which is expressed in both the sex gametocytes of P. falciparum but is upregulated specifically in male gametocytes.…”

Section: Genes Associated With Gametocyte Activationmentioning

confidence: 99%

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in Plasmodium falciparum: a review of current knowledge and future directions

Varijakshi,

Divya,

Ware

et al. 2023

3 Biotech

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Utilizing transcriptomics, promising methods for identifying unique genes associated with Plasmodium gametocyte development offer a potential avenue for novel candidate targets in transmission blocking vaccine development. In this review, we identified 40 publicly available transcriptomic datasets related to parasite factors linked with sexual stage transmission, from which we analyzed two RNA-Seq datasets to identify potential genes crucial for the transmission of P. falciparum from humans to mosquito vectors. Differential expression analysis revealed 3500 (2489 upregulated and 1011 downregulated) common genes differentially expressed throughout sexual stage development of P. falciparum occurring in both humans (gametocyte stage II, V) and mosquitoes (ookinete). Among which 1283 (914 upregulated and 369 downregulated) and 826 (719 upregulated and 107 downregulated) genes were specific to female and male gametocytes, respectively. Also, 830 potential transition associated genes were identified that may be involved in the adaptation and survival of the parasite in between human and mosquito stages. Additionally, we reviewed the functional aspects of important genes highly expressed throughout the sexual stage pathway and evaluated their suitability as vaccine candidates. The review provides researchers with insight into the importance of publicly available transcriptomic datasets for identifying critical and novel gametocyte markers that may aid in the development of rational transmission blocking strategies.

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“…Antibodies against specific epitopes of these antigens reduced transmission of P. falciparum parasites ( 10 – 14 ), supporting further investigation of these antigens as potential TBVs ( 15 ). Initiatives to identify ( 16 ) and characterize ( 17 , 18 ) novel TBV candidates have been stimulated by the availability of sexual stage specific transcriptome ( 19 ) and proteome datasets ( 20 , 21 ). These studies demonstrated that antigens enolase ( 17 ), Pf77 and PfMDV1 ( 18 ) induce antibodies with transmission reducing activity (TRA) in mice.…”

Section: Introductionmentioning

confidence: 99%

“…Initiatives to identify ( 16 ) and characterize ( 17 , 18 ) novel TBV candidates have been stimulated by the availability of sexual stage specific transcriptome ( 19 ) and proteome datasets ( 20 , 21 ). These studies demonstrated that antigens enolase ( 17 ), Pf77 and PfMDV1 ( 18 ) induce antibodies with transmission reducing activity (TRA) in mice. However, future studies are needed to determine whether the observed efficacy is reproducible and should include the optimization of protein expression and vaccine formulations.…”

Section: Introductionmentioning

confidence: 99%

Heterologous Expression and Evaluation of Novel Plasmodium falciparum Transmission Blocking Vaccine Candidates

Jong

Singh²,

Teelen³

et al. 2022

Front. Immunol.

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Malaria transmission blocking vaccines (TBV) aim to induce antibodies that can interrupt Plasmodium falciparum development in the mosquito midgut and thereby prevent onward malaria transmission. A limited number of TBV candidates have been identified and only three (Pfs25, Pfs230 and Pfs48/45) have entered clinical testing. While one of these candidates may emerge as a highly potent TBV candidate, it is premature to determine if they will generate sufficiently potent and sustained responses. It is therefore important to explore novel candidate antigens. We recently analyzed sera from naturally exposed individuals and found that the presence and/or intensity of antibodies against 12 novel putative surface expressed gametocyte antigens was associated with transmission reducing activity. In this study, protein fragments of these novel TBV candidates were designed and heterologously expressed in Drosophila melanogaster S2 cells and Lactococcus lactis. Eleven protein fragments, covering seven TBV candidates, were successfully produced. All tested antigens were recognized by antibodies from individuals living in malaria-endemic areas, indicating that native epitopes are present. All antigens induced antigen-specific antibody responses in mice. Two antigens induced antibodies that recognized a native protein in gametocyte extract, and antibodies elicited by four antigens recognized whole gametocytes. In particular, we found that antigen Pf3D7_0305300, a putative transporter, is abundantly expressed on the surface of gametocytes. However, none of the seven novel TBV candidates expressed here induced an antibody response that reduced parasite development in the mosquito midgut as assessed in the standard membrane feeding assay. Altogether, the antigen fragments used in this study did not prove to be promising transmission blocking vaccine constructs, but led to the identification of two gametocyte surface proteins that may provide new leads for studying gametocyte biology.

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Plasmodium falciparum Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies

Cited by 8 publications

References 59 publications

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Host-parasite interactions during Plasmodium infection: Implications for immunotherapies

Transcriptomic approaches for identifying potential transmission blocking vaccine candidates in Plasmodium falciparum: a review of current knowledge and future directions

Heterologous Expression and Evaluation of Novel Plasmodium falciparum Transmission Blocking Vaccine Candidates

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