Jordan's presentation at the Oxford/Pirbright B cell meeting

Jordan Barrett presented at the Oxford/Pirbright B cell meeting on Thursday, 5 May 2022. The meeting took place at the Dorfman Centre, St Peter's College, Oxford and was co-organised by Dr Carolyn Nielsen. 

A summary of Jordan's presentation follows below:

Plasmodium vivax is the most widespread of all malaria species, and can cause severe and recurrent infections. P. vivax invades immautre reticulocytes during the blood-stage of the infection, through an essential interaction between the parasites duffy-binding protein (DBP) and the host reticulocyte's Duffy antigen/receptor for chemokines (DARC). As part of Draper group clinical trials, we tested the leading blood-stage vaccine candidate for vivax malaria, DBP_RII, in viral vectored or protein-in-adjuvant formulations using either monthly or delayed dosing regimens in humans. Delayed dosing was found to improve several immunological readouts in the serum, including greater antibody titre and improved functionality of antibodies. Delayed dosing regimens also significantly slowed parasite growth rates in a human infection model. Using a B cell flow cytometry panel with DBP_RII probes, we measured vaccine-induced B cell responses to investigate the underlying mechanisms for this improved humoral immunity. We found that the delayed dosing regimen significantly increases the frequency of plasma cells, DBP-specific IgG+ and IgA+ memory B cells, DBP-specific plasmablasts, and proliferating memory B cells. A number of these parameters correlated with the slowed parasite growth rates in the human infection model and provided a possible correlate of serum antibody longevity. Through the use of dimensonality reduction and clustering algorithims, we identfied a possible anergic B cell population that is less frequent in the delayed dosing regimen. This suggests that vaccination regimens with shorter dose intervals produce a lower humoral response due to the induction of B cell anergy from chronic antigen exposure. Upcoming vaccine trials, and the inclusion of new markers in the panel, will help us test this hypothesis and inform new vaccination regimens.