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. 2024 Sep 17;42(22):126205.
doi: 10.1016/j.vaccine.2024.126205. Epub 2024 Aug 13.

Immunogenicity of a 30-valent M protein mRNA group A Streptococcus vaccine

Meredith B Finn  1 , Thomas A Penfound  2 , Sanaz Salehi  2 , Clinton O Ogega  1 , Christina Dold  1 , Obadiah Plante  3 , James B Dale  4
Affiliations

Immunogenicity of a 30-valent M protein mRNA group A Streptococcus vaccine

Meredith B Finn et al. Vaccine. .

Abstract

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.

Keywords: Group A Streptococcus; M-protein; Multivalent; Vaccine; mRNA.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MBF, COO, CD, and OP are employees of Moderna, Inc. and may hold stock or stock options. JBD is the inventor of certain technologies related to the development of group A streptococcal vaccines. The technology is owned by the University of Tennessee Research Foundation.

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