Journal
VACCINE
Volume 41, Issue 28, Pages 4170-4182Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2023.05.031
Keywords
Streptococcus pneumoniae; PspA; Vaccines; Bordetella CyaA; Delivery systems; Animal models
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Streptococcus pneumoniae is a common pathogen causing important human diseases. Current vaccines have limited efficacy and can only protect against specific serotypes. Pneumococcal Surface Protein A (PspA) is an important vaccine candidate due to its role in evading the host immune system. Researchers have tested a delivery system based on the Bordetella pertussis adenylate cyclase toxin to induce immune responses against PspA in mice.
Streptococcus pneumoniae is a common agent of important human diseases such as otitis media, pneumo-nia, meningitis and sepsis. Current available vaccines that target capsular polysaccharides induce protec-tion against invasive disease and nasopharyngeal colonization in children, yet their efficacy is limited to the serotypes included in the formulations. The virulence factor Pneumococcal Surface Protein A (PspA) interacts with host immune system and helps the bacteria to evade phagocytosis. Due to its essential role in virulence, PspA is an important vaccine candidate. Here we have tested a delivery system based on the adenylate cyclase toxin of Bordetella pertussis (CyaA) to induce immune responses against PspA in mice. CyaA was engineered to express fragments of the N-terminal region of PspAs from clades 2 and 4 (A2 and A4) and the resulting proteins were used in immunization experiments in mice. The recombinant CyaA-A2 and CyaA-A4 proteins were able to induce high levels of anti-PspA antibodies that reacted with pneu-mococcal strains expressing either PspA2 or PspA4. Moreover, reactivity of the antibodies against pneu-mococcal strains that express PspAs from clades 3 and 5 (PspA3 and PspA5) was also observed. A formulation containing CyaA-A2 and CyaA-A4 was able to protect mice against invasive pneumococcal challenges with isolates that express PspA2, PspA4 or PspA5. Moreover, a CyaA-A2-A4 fusion protein induced antibodies at similar levels and with similar reactivity as the formulation containing both pro-teins, and protected mice against the invasive challenge. Our results indicate that CyaA-PspA proteins are good candidates to induce broad protection against pneumococcal isolates. & COPY; 2023 Elsevier Ltd. All rights reserved.
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