Invited Speaker CD1-MR1 Workshop 2025

Mechanisms of follicular helper NKT cell-mediated augmentation of antibody production by a pneumococcal protein and glycolipid vaccine (#52)

Yuki Kinjo 1 2 , Koji Hayashizaki 1 2 , Shogo Takatsuka 3 , Yasuhiro Kamii 1 2 , Taku Ikegami 1 2 , Shinya Sugimoto 1 2 , Toshio Kanno 4 , Mitchell Kronenberg 5 , Yusuke Endo 4
  1. The Jikei University School of Medicine, Minato-ku, TOKYO, Japan
  2. Department of Bacteriology, The Jikei University School of Medicine, Tokyo, Japan
  3. Department of Fungal Infection, National Institute of Infectious Diseases, Tokyo, Japan
  4. Department of Frontier Research and Development, Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Chiba, Japan
  5. La Jolla Institute for Immunology, La Jolla, USA

Antigen-specific antibody production is crucial for protection against infection with extracellular bacteria such as Streptococcus pneumoniae (Pneumococcus), which is the leading cause of community-acquired pneumonia. Thus, an effective vaccine that induces sustained antibody production is desired. We utilized the feature of NKT cells that stimulates humoral immunity and established a protein-based pneumococcal vaccine with α-galactosylceramide as an adjuvant. This vaccine induced potent and prolonged, high affinity antigen-specific IgG production compared to other adjuvant-containing vaccines, and provided protection against S. pneumoniae infection. Moreover, we found that this vaccine effect was dependent on CXCR5+ PD1+ follicular helper NKT (NKTFH) cells that produce interleukin-21. In this presentation, we will describe the mechanism of how myeloid cells and NKTFH cells contribute to vaccination and discuss the involvement of a non-canonical B cell population that cooperates with NKT cells.