Protective immunity against invasive Streptococcus pneumoniae infections by tissue-specific memory Th17 cells (P4266)

Abstract

Abstract Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Current vaccine is highly effective in preventing colonization by inducing serotype-specific antibodies. However, there is an increasing prevalence of infection by serotype strains not included in the vaccine; this highlights the need for a universal vaccine that protects against all serotypes. The first step in developing a universal vaccine is to elucidate the immune mechanism that can provide broad protection against different serotype Sp strains. We found that intranasal immunization of mice with Sp resulted in a strong CD4+T cell response in the lung that consisted of mostly Th17 cells but also IFNγ producing Th1 cells. These immunized mice were protected against lethal challenge with a different serotype strain of Sp and cleared bacteria in lung by day 2 post-challenge. Adoptive transfer of T cells from immunized mice also provided protection against a heterologous challenge, with a dominant Th17 recall response in the lung from donor memory T cells. Furthermore, immunization of mice with Listeria monocytogenes (LM) provided protection against a recombinant Sp strain expressing a CD4 epitope from LM (LLO190), as shown by decreased CFU in the lung, and elevated LLO190-specific Th17 response. Our results suggest that memory Th17 cells may play a key role in providing broad protective immunity against invasive Sp infection in a serotype independent manner.