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Immunogenicity of a 30-valent M protein mRNA group A Streptococcus vaccine
Meredith B Finn1, Thomas A Penfound2, Sanaz Salehi2
1Moderna, Inc., 325 Binney St., Cambridge, MA 02142, USA.
Background:
Group A Streptococcus (Strep A) causes both uncomplicated and severe invasive infections, as well as the post-infection complications acute rheumatic fever and rheumatic heart disease. Despite the high global burden of disease resulting from Strep A infections, there is not a licensed vaccine. A 30-valent M protein-based vaccine has previously been shown to be immunogenic in animal models and in a Phase I clinical trial (NCT02564237). Here, we assessed the immunogenicity of a 30-valent messenger (m)RNA vaccine designed to express the same M peptide targets as the 30-valent protein vaccine and compared it with the protein vaccine.
Methods:
Female New Zealand white rabbits were immunized with one of four vaccine formulations (3 doses of each formulation at days 1, 28, and 56): soluble mRNA (100 μg/animal), C-terminal transmembrane mRNA (100 μg/animal), protein vaccine (400 μg/animal), or a non-translatable RNA control (100 μg/animal). Serum was collected one day prior to the first dose and on days 42 and 70. Rabbit serum samples were assayed for antibody levels against synthetic M peptides by ELISA. HL-60 opsonophagocytic killing (OPK) assays were performed to assess functional antibody levels.
Results:
Serum IgG levels were similar for the mRNA and protein vaccines. The CtTM version of the mRNA vaccine elicited slightly higher antibody levels than the mRNA designed to express soluble proteins. OPK activity was similar for the mRNA and protein vaccines, regardless of M type.
Conclusions:
The total antibody responses and functional antibody levels elicited by the 30-valent mRNA Strep A vaccines were similar to those observed following immunization with the analogous protein vaccine. The mRNA vaccine platform provides potential advantages to protein-based vaccines including inherent adjuvant activity, increased production efficiency, lower cost, and the potential to rapidly change epitopes/peptides, all of which are important considerations related to multivalent Strep A vaccine development.
Insights
A new 30-valent messenger RNA (mRNA) vaccine for Group A Streptococcus (Strep A) showed similar immunogenicity to a protein-based vaccine. This mRNA vaccine platform offers potential advantages for developing a much-needed Strep A vaccine.
Area of Science:
- Vaccinology
- Microbiology
- Immunology
Background:
- Group A Streptococcus (Strep A) causes significant global disease, including acute rheumatic fever and rheumatic heart disease.
- Currently, no licensed Strep A vaccine is available, despite the high disease burden.
- A previous 30-valent M protein vaccine demonstrated immunogenicity in preclinical and early clinical studies.
Purpose of the Study:
- To assess the immunogenicity of a 30-valent mRNA Strep A vaccine.
- To compare the immunogenicity of the mRNA vaccine with a 30-valent protein vaccine.
Main Methods:
- New Zealand white rabbits were immunized with four formulations: soluble mRNA, C-terminal transmembrane mRNA, protein vaccine, or RNA control.
- Three doses were administered on days 1, 28, and 56.
- Serum IgG levels and functional antibody levels (opsonophagocytic killing assays) were measured on days 42 and 70.
Main Results:
- Both mRNA and protein vaccines induced similar serum IgG levels.
- The C-terminal transmembrane mRNA formulation showed slightly higher antibody levels compared to the soluble mRNA formulation.
- Opsonophagocytic killing activity was comparable between mRNA and protein vaccines across different M types.
Conclusions:
- The 30-valent mRNA Strep A vaccines elicited comparable total and functional antibody responses to the analogous protein vaccine.
- The mRNA platform presents potential benefits over protein vaccines, including inherent adjuvant properties, improved production efficiency, reduced cost, and adaptability for epitope changes.
- These advantages are significant for the development of multivalent Strep A vaccines.
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