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PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
Chen-Fang Hsu1,2,3,4, Chen-Hao Hsiao5,6, Shun-Fu Tseng7
1Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan.
Insights
A novel pneumococcal protein A (PrtA) vaccine candidate, when administered intranasally with curdlan adjuvant, failed to protect mice against Streptococcus pneumoniae infection. Despite eliciting immune responses, PrtA immunization did not prevent pneumonia or bacteremia in a murine model.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Streptococcus pneumoniae causes severe lung infections and bacteremia.
- Current polysaccharide vaccines offer limited serotype coverage.
- Developing a conserved protein vaccine for S. pneumoniae is a global priority.
Purpose of the Study:
- To evaluate the protective efficacy of intranasal immunization with a pneumococcal surface protein A (PrtA) fragment combined with curdlan adjuvant.
- To assess the resulting T-cell and antibody responses against S. pneumoniae.
Main Methods:
- BALB/c mice were immunized intranasally with a PrtA fragment and curdlan adjuvant.
- Immune responses, including T-cell and antibody production, were measured.
- Protective efficacy was evaluated in murine models of acute pneumococcal pneumonia and bacteremia.
Main Results:
- Intranasal PrtA immunization induced antigen-specific IL-17A and IFN-γ responses.
- Elevated PrtA-specific IgG and IgA titers were observed in sera, with moderate IgA in bronchoalveolar lavage fluid.
- Antisera facilitated opsonophagocytosis of S. pneumoniae by macrophages, but with limited potency; protection against pneumonia and bacteremia was not achieved.
Conclusions:
- Recombinant PrtA combined with curdlan adjuvant elicits antigen-specific antibodies and IL-17A responses.
- This immunization strategy failed to protect mice against S. pneumoniae-induced pneumonia and bacteremia.
Background:
Streptococcus pneumoniae is a respiratory pathogen causing severe lung infection that may lead to complications such as bacteremia. Current polysaccharide vaccines have limited serotype coverage and therefore cannot provide maximal and long-term protection. Global efforts are being made to develop a conserved protein vaccine candidate. PrtA, a pneumococcal surface protein, was identified by screening a pneumococcal genomic expression library using convalescent patient serum. The prtA gene is prevalent and conserved among S. pneumoniae strains. Its protective efficacy, however, has not been described. Mucosal immunization could sensitize both local and systemic immunity, which would be an ideal scenario for preventing S. pneumoniae infection.
Methods:
We immunized BALB/c mice intranasally with a combination of a PrtA fragment (amino acids 144-1041) and Th17 potentiated adjuvant, curdlan. We then measured the T-cell and antibody responses. The protective efficacy conferred to the immunized mice was further evaluated using a murine model of acute pneumococcal pneumonia and pneumococcal bacteremia.
Results:
There was a profound antigen-specific IL-17A and IFN-γ response in PrtA-immunized mice compared with that of adjuvant control group. Even though PrtA-specific IgG and IgA titer in sera was elevated in immunized mice, only a moderate IgA response was observed in the bronchoalveolar lavage fluid. The PrtA-immunized antisera facilitated the activated murine macrophage, RAW264.7, to opsonophagocytose S. pneumoniae D39 strain; however, PrtA-specific immunoglobulins bound to pneumococcal surfaces with a limited potency. Finally, PrtA-induced immune reactions failed to protect mice against S. pneumoniae-induced acute pneumonia and bacterial propagation through the blood.
Conclusions:
Immunization with recombinant PrtA combined with curdlan produced antigen-specific antibodies and elicited IL-17A response. However, it failed to protect the mice against S. pneumoniae-induced infection.
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