Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

Background Although vaccination is recommended for protection against invasive pneumococcal disease, the frequency of pneumococcal pneumonia is still high worldwide. In fact, no vaccines are effective for all pneumococcal serotypes. Fusion pneumococcal surface protein A (PspA) has been shown to induce a broad range of cross-reactivity with clinical isolates and afford cross-protection against pneumococcal challenge in mice. Furthermore, we developed prime-boost-type mucosal vaccines that induce both antigen-specific IgG in serum and antigen-specific IgA in targeted mucosal organs in previous studies. We investigated whether our prime-boost-type immunization with a fusion PspA was effective against pneumococcal infection in mice and cynomolgus macaques. Methods C57BL/6 mice were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan. Six weeks later, PspA was administered intranasally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some mice were given intranasal Streptococcus pneumoniae and the severity of infection was analyzed. Macaques were intramuscularly injected with fusion PspA combined with CpG oligodeoxynucleotides and/or curdlan at week 0 and week 4. Then, 13 or 41 weeks later, PspA was administered intratracheally. Blood and bronchoalveolar lavage fluid were collected and antigen-specific IgG and IgA titers were measured. Some macaques were intranasally administered S. pneumoniae and analyzed for the severity of pneumonia. Results Serum samples from mice and macaques injected with antigens in combination with CpG oligodeoxynucleotides and/or curdlan contained antigen-specific IgG. Bronchial samples contained antigen-specific IgA after the fusion PspA boosting. This immunization regimen effectively prevented S. pneumoniae infection. Conclusions Prime-boost-type immunization with a fusion PspA prevented S. pneumoniae infection in mice and macaques.

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Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

Cited by 2 publications

References 41 publications

High prevalence of 19A pneumococcal serotype carriage during the COVID-19 pandemic in Brazil

High prevalence of 19A pneumococcal serotype carriage during the COVID-19 pandemic in Brazil

Prime-boost-type PspA3 + 2 mucosal vaccine protects cynomolgus macaques from intratracheal challenge with pneumococci

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