An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i>
Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage <i>Plasmodium</i> parasites, we completed a proof-of-concept study using the <i>P. yoelii</i> mouse model of malaria and two mRNA-based vaccines. Both encoded <i>Py</i>MSP1<sub>...
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MDPI AG
2025-06-01
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| author | Amy C. Ott Patrick J. Loll James M. Burns |
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| description | Background and Objectives: To evaluate the mRNA vaccine platform for blood-stage <i>Plasmodium</i> parasites, we completed a proof-of-concept study using the <i>P. yoelii</i> mouse model of malaria and two mRNA-based vaccines. Both encoded <i>Py</i>MSP1<sub>19</sub> fused to <i>Py</i>MSP8 (<i>Py</i>MSP1/8). One was designed for secretion of the encoded protein (<i>Py</i>MSP1/8-sec); the other encoded membrane-bound antigen (<i>Py</i>MSP1/8-mem). Methods: Secretion of <i>Py</i>MSP1/8-sec and membrane localization of <i>Py</i>MSP1/8-mem were verified in mRNA-transfected cells. As recombinant <i>Py</i>MSP1/8 (r<i>Py</i>MSP1/8) is known to protect mice against lethal <i>P. yoelii</i> 17XL infection, we first compared immunogenicity and efficacy of the <i>Py</i>MSP1/8-sec mRNA vaccine versus the recombinant formulation in outbred mice. Animals were immunized three times followed by challenge with a lethal dose of <i>P. yoelii</i> 17XL-parasitized RBCs (pRBCs). Similar immunization and challenge experiments were conducted to compare <i>Py</i>MSP1/8-sec versus <i>Py</i>MSP1/8-mem mRNA vaccines. Results: Immunogenicity of the <i>Py</i>MSP1/8-sec mRNA vaccine was superior to the recombinant formulation, inducing higher antibody titers against both vaccine components. Following challenge with <i>P. yoelii</i> 17XL pRBCs, all <i>Py</i>MSP1/8-sec-immunized animals survived, with 50% of these showing no detectible pRBCs in circulation (<0.01%). In addition, mean peak parasitemia in <i>Py</i>MSP1/8-sec mRNA-immunized mice was significantly lower than that in the r<i>Py</i>MSP1/8 vaccine group. Both <i>Py</i>MSP1/8-sec and <i>Py</i>MSP1/8-mem were protective against <i>P. yoelii</i> 17XL challenge, with <i>Py</i>MSP1/8-mem immunization providing a significantly higher level of protection than <i>Py</i>MSP1/8-sec immunization considering the number of animals with no detectable pRBCs in circulation and the mean peak parasitemia in animals with detectable parasitemia. Conclusions: mRNA vaccines were highly immunogenic and potently protective against blood-stage malaria, outperforming a similar recombinant-based vaccine. The membrane-bound antigen was more effective at inducing protective antibody responses, highlighting the need to consider antigen localization for mRNA vaccine design. |
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| spelling | doaj-art-e3ddf0fff43b4920be57e5f7785a5cd42025-07-25T13:38:19ZengMDPI AGVaccines2076-393X2025-06-0113770210.3390/vaccines13070702An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i>Amy C. Ott0Patrick J. Loll1James M. Burns2Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA 19129, USADepartment of Biochemistry and Molecular Biology, Drexel University College of Medicine, 215 North 15th St., Philadelphia, PA 19102, USACenter for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA 19129, USABackground and Objectives: To evaluate the mRNA vaccine platform for blood-stage <i>Plasmodium</i> parasites, we completed a proof-of-concept study using the <i>P. yoelii</i> mouse model of malaria and two mRNA-based vaccines. Both encoded <i>Py</i>MSP1<sub>19</sub> fused to <i>Py</i>MSP8 (<i>Py</i>MSP1/8). One was designed for secretion of the encoded protein (<i>Py</i>MSP1/8-sec); the other encoded membrane-bound antigen (<i>Py</i>MSP1/8-mem). Methods: Secretion of <i>Py</i>MSP1/8-sec and membrane localization of <i>Py</i>MSP1/8-mem were verified in mRNA-transfected cells. As recombinant <i>Py</i>MSP1/8 (r<i>Py</i>MSP1/8) is known to protect mice against lethal <i>P. yoelii</i> 17XL infection, we first compared immunogenicity and efficacy of the <i>Py</i>MSP1/8-sec mRNA vaccine versus the recombinant formulation in outbred mice. Animals were immunized three times followed by challenge with a lethal dose of <i>P. yoelii</i> 17XL-parasitized RBCs (pRBCs). Similar immunization and challenge experiments were conducted to compare <i>Py</i>MSP1/8-sec versus <i>Py</i>MSP1/8-mem mRNA vaccines. Results: Immunogenicity of the <i>Py</i>MSP1/8-sec mRNA vaccine was superior to the recombinant formulation, inducing higher antibody titers against both vaccine components. Following challenge with <i>P. yoelii</i> 17XL pRBCs, all <i>Py</i>MSP1/8-sec-immunized animals survived, with 50% of these showing no detectible pRBCs in circulation (<0.01%). In addition, mean peak parasitemia in <i>Py</i>MSP1/8-sec mRNA-immunized mice was significantly lower than that in the r<i>Py</i>MSP1/8 vaccine group. Both <i>Py</i>MSP1/8-sec and <i>Py</i>MSP1/8-mem were protective against <i>P. yoelii</i> 17XL challenge, with <i>Py</i>MSP1/8-mem immunization providing a significantly higher level of protection than <i>Py</i>MSP1/8-sec immunization considering the number of animals with no detectable pRBCs in circulation and the mean peak parasitemia in animals with detectable parasitemia. Conclusions: mRNA vaccines were highly immunogenic and potently protective against blood-stage malaria, outperforming a similar recombinant-based vaccine. The membrane-bound antigen was more effective at inducing protective antibody responses, highlighting the need to consider antigen localization for mRNA vaccine design.https://www.mdpi.com/2076-393X/13/7/702malaria<i>Plasmodium</i><i>Plasmodium yoelii</i>vaccinesmRNAblood-stage malaria |
| spellingShingle | Amy C. Ott Patrick J. Loll James M. Burns An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> Vaccines malaria <i>Plasmodium</i> <i>Plasmodium yoelii</i> vaccines mRNA blood-stage malaria |
| title | An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> |
| title_full | An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> |
| title_fullStr | An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> |
| title_full_unstemmed | An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> |
| title_short | An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal <i>Plasmodium yoelii</i> |
| title_sort | mrna vaccine expressing blood stage malaria antigens induces complete protection against lethal i plasmodium yoelii i |
| topic | malaria <i>Plasmodium</i> <i>Plasmodium yoelii</i> vaccines mRNA blood-stage malaria |
| url | https://www.mdpi.com/2076-393X/13/7/702 |
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