Vaccines have eliminated and reduced the burden of many diseases, but highly protective vaccines remain unavailable for major infectious diseases like malaria, which is a top 5 killer of children globally. Antibodies play a crucial role in malaria immunity, and their development occurs predominantly in the germinal centres (GCs) within the secondary lymphoid organs. However, in vivo studies of the human immune system are often constrained by the limited accessibility of lymphoid tissues. Thus, there is an urgent need to develop a high-throughput, robust, and accessible system that models the dynamics of antigen-specific humoral and GC responses. Here, we utilised tonsil-derived lymphoid culture systems recently developed to study humoral and cellular responses to different types of vaccines and malaria parasites. Using this system, we show that our tonsil-derived lymphoid culture model recapitulates key aspects of human lymphoid tissue and allows investigation of antigen-specific B cells, GC formation, and antibody production in response to different types of vaccines, including inactivated, live-attenuated, and mRNA vaccines as well as malaria parasites. With tonsil cells from malaria-naïve, malaria-exposed, and asymptomatically infected children, this model provides a scalable platform to study human vaccine responses and potentially accelerate the development of effective vaccines against malaria.