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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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/7/702 |
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| Summary: | 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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| ISSN: | 2076-393X |