Malaria infection remains a significant and persistent threat and causes high levels of morbidity and mortality every year. Disease control and prevention requires the use of multiple approaches such as vector control with insecticides, parasite control with effective drugs. Malaria vaccines have been identified as an additional tool for control and prevention but the only licensed vaccine, RTS.S only provides very modest efficacy against severe disease in children. There is therefore an urgent need to develop more effective vaccines. A prominent strategy for malaria vaccine development is to target the pre-erythrocytic stage parasites so they do not progress to the disease-causing blood stages. Parasite antigens that elicit potent T cell responses, especially those that express interferon-Gamma (IFN-ɣ) and granzyme B (GrzB), are very efficient at killing the liver stages of the parasite. Another important consideration in designing antigen-based vaccines is to avoid the limitation that antigen polymorphisms place on the effectiveness of elicited immune responses. We have incorporated in our research strategies that either focus the immune response on conserved immunodominant portions of essential parasite antigens or dilute out the polymorphic portions. Our long-term goal is to identify and characterize HLA class I and II-restricted peptides from essential malaria parasite antigen fragments that are conserved and have the capacity to elicit potent IFN-ɣ and GrzB responses, with the ultimate aim of incorporating these into universally effective multi-epitope malaria vaccines.