Enhanced Broad-Spectrum Efficacy of an L2-Based mRNA Vaccine Targeting HPV Types 6, 11, 16, 18, with Cross-Protection Against Multiple Additional High-Risk Types
Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and develop...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/12/11/1239 |
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| Summary: | Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and developed a multivalent L2-based mRNA vaccine encoding L2 aa 2-130, which includes all known neutralizing epitopes from four prevalent HPV types (HPV-6, -11, -16, and -18). We evaluated its immunogenicity in a mouse model and compared the efficacy of a commercially available mRNA delivery reagent with a custom-synthesized lipid nanoparticle (LNP) formulation. Results: We identified that a construct containing E01 (a 5′-untranslated region) and SL2.7 (a poly(A) polymerase recruitment sequence) significantly increased protein expression. The L2-based mRNA vaccine induced robust and long-lasting humoral immune responses, with significant titers of cross-reactive serum IgG antibodies against L2 epitopes. Notably, the vaccine elicited cross-neutralizing antibodies and conferred cross-protective immunity not only against vaccine-targeted HPV types but also against non-vaccine HPV types, following intravaginal challenge in mice. We also found that LNP delivered mRNA more effectively in vivo. Conclusions: The L2-based mRNA vaccine developed in this study shows significant potential for broad-spectrum protection against multiple HPV types. This approach offers a promising strategy for reducing the global burden of HPV-associated cancers. |
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| ISSN: | 2076-393X |