Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to Infection

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.