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Published on: January 17, 2014
Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to
Giuliana S Oliveira1, Johanna Rivera2, Tasson C Rodrigues1
1Bacteriology Laboratory, Instituto Butantan, São Paulo, Brazil.
Background:
Streptococcus pneumoniae (pneumococcus) is a common cause of respiratory and invasive infections in humans. PCV13, a pneumococcal conjugate vaccine used globally, is highly effective against diseases caused by pneumococcal serotypes included in its formulation. However, one of them, the serotype 3 (ST3) is still being relatively commonly isolated from patients, suggesting an escape from vaccine-induced immunity. The thick capsule produced by ST3 facilitates bacterial evasion from the immune system. Additionally, host immune responses may influence the outcome of ST3 infection. Here we evaluated the influence of inflammation in the adaptive immune responses and protection induced by PCV13 against ST3, using two outbred mice lines that were phenotypically selected for high (AIRmax) and low (AIRmin) inflammatory responses.
Methods:
AIRmin and AIRmax mice were immunized with PCV13. Inbred BALB/c mice were used as reference for vaccine efficacy. Induction of IgG against polysaccharides (PS) from pneumococcal serotype 1 (ST1) and ST3 were evaluated by ELISA. Protection was tested against invasive infections with ST1 and ST3 pneumococcal strains. Sera were compared by IgG binding to pneumococcal surface, induction of pneumococcal agglutination and opsonophagocytosis. The phagocytic capacity of mice-derived neutrophils was also evaluated.
Results:
Immunization of AIRmin, AIRmax and BALB/c mice with PCV13 induced IgG against PS from ST1 and ST3 pneumococci. Despite vaccination, AIRmin mice were not protected against fatal infection with ST3. Sera from AIRmin mice immunized with PCV13 presented lower levels of anti-PS3 IgG, with reduced capacity to bind to pneumococcal surface. Reduced capacity to induce opsonophagocytosis of ST3 pneumococci in vitro was also observed. Conversely, PCV13 protected AIRmin mice against fatal infection with ST1 and this correlated with the capacity of the sera to induce ST1 opsonophagocytosis.
Conclusions:
Our results show that both host and bacterial features can influence the outcome of protection induced by PCV13 against ST3 pneumococcal infection.
Insights
The pneumococcal conjugate vaccine PCV13 effectively protects against most strains, but not serotype 3 (ST3) in mice with low inflammatory responses. Host immune factors influence vaccine efficacy against ST3 infections.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Streptococcus pneumoniae causes respiratory and invasive infections.
- The pneumococcal conjugate vaccine PCV13 is effective but less so against serotype 3 (ST3).
- ST3's capsule aids immune evasion, and host responses impact infection outcomes.
Purpose of the Study:
- To evaluate the influence of inflammation on adaptive immune responses and PCV13 protection against ST3.
- To compare PCV13 efficacy in mice with high (AIRmax) and low (AIRmin) inflammatory responses.
Main Methods:
- Mice (AIRmin, AIRmax, BALB/c) were immunized with PCV13.
- Antibody levels (IgG) against ST1 and ST3 polysaccharides were measured.
- Protection against invasive ST1 and ST3 infections was assessed.
- Sera were analyzed for bacterial surface binding, agglutination, and opsonophagocytosis.
Main Results:
- PCV13 induced IgG against ST1 and ST3 in all mouse groups.
- AIRmin mice, despite vaccination, were not protected against ST3 infection.
- AIRmin mice showed lower anti-ST3 IgG, reduced bacterial binding, and impaired opsonophagocytosis of ST3.
- PCV13 protected AIRmin mice against ST1, correlating with effective opsonophagocytosis.
Conclusions:
- Host and bacterial factors influence PCV13 protection against ST3.
- Low inflammatory responses in AIRmin mice compromise vaccine efficacy against ST3.
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