Invited Speaker Oral Presentation Lorne Infection and Immunity 2023

Can a B cell eat a parasite? (#41)

Ian Cockburn 1
  1. Australian National University, Canberra, ACT, Australia

Malaria caused by Plasmodium infection kills around 600,000 people each year, demonstrating a clear need for a safe and effective vaccine. In clinical trials the RTS,S and R21 subunit vaccines confer modest protection for less than a year. Another, whole parasite, vaccine performs well in malaria naïve volunteers but is less efficacious in endemic areas. These vaccines work in large measure by the generation of antibody and T cell responses to the circumsporozoite protein (CSP). To better understand the factors shaping these immune responses to both subunit and whole parasites we have developed CSP-specific BCR knockin and TCR transgenic mice. Using these tools we find that the requirements for immune responses to whole parasites are different to those for subunit vaccines. In particular, B cells interacting with whole parasites have an opportunity to obtain T cell help from diverse sources that may facilitate sustained germinal center responses. These sustained germinal center responses can generate long lived plasma cells. However, this response is also limited by antibody feedback. Our results highlight the need to study B cell responses to whole pathogens as well as simple immunogens to determine how sustained responses can be generated by vaccination.