Polymeric epitope-based vaccine induces protective immunity against group A Streptococcus

Autor: Shuxiong Chen, Victoria Ozberk, Gayathri Sam, Zennia Jean C. Gonzaga, Ainslie Calcutt, Manisha Pandey, Michael F. Good, Bernd H. A. Rehm
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: npj Vaccines, Vol 8, Iss 1, Pp 1-11 (2023)
Druh dokumentu: article
ISSN: 2059-0105
38568543
DOI: 10.1038/s41541-023-00695-x
Popis: Abstract Group A Streptococcus (Strep A) is a life-threatening human pathogen with no licensed vaccine. Here, we used a biopolymer particle (BP) approach to display repeats of Strep A vaccine candidate peptides p*17 and K4S2 derived from M and non-M protein, respectively. BPs densely displaying both peptides (BP-p*17-S2) were successfully assembled in one-step inside an engineered endotoxin-free Escherichia coli strain. Purified BP-p*17-S2 showed a spherical core-shell morphology with a biopolymer core and peptide shell. Upon formulation with aluminum hydroxide as adjuvant, BP-p*17-S2 exhibited a mean diameter of 2.9 µm and a positive surface charge of 22 mV. No cytotoxicity was detected when tested against HEK-293 cells. Stability studies showed that BP-p*17-S2 is ambient-temperature stable. Immunized mice showed no adverse reactions, while producing high titers of peptide specific antibodies and cytokines. This immune response could be correlated with protective immunity in an animal model of infection, i.e. intranasal challenge of mice with Strep A, where a significant reduction of >100-fold of pathogen burden in nose-associated lymphoid tissue, lung, and spleen was obtained. The cost-effective scalable manufacture of ambient-temperature stable BPs coated with Strep A peptides combined with their immunogenic properties offer an attractive alternative strategy to current Strep A vaccine development.
Databáze: Directory of Open Access Journals
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