Immune tolerance caused by repeated P. falciparum infection against SE36 malaria vaccine candidate antigen and the resulting limited polymorphism.

The call for second generation malaria vaccines needs not only the identification of novel candidate antigens or adjuvants but also a better understanding of immune responses and the underlying protective processes. Plasmodium parasites have evolved a range of strategies to manipulate the host immune system to guarantee survival and establish parasitism. These immune evasion strategies hamper efforts to develop effective malaria vaccines. In the case of a malaria vaccine targeting the N-terminal domain of P. falciparum serine repeat antigen 5 (SE36), now in clinical trials, we observed reduced responsiveness (lowered immunogenicity) which may be attributed to immune tolerance/immune suppression. Here, immunogenicity data and insights into the immune responses to SE36 antigen from epidemiological studies and clinical trials are summarized. Documenting these observations is important to help identify gaps for SE36 continued development and engender hope that highly effective blood-stage/multi-stage vaccines can be achieved.
Competing Interests: Declaration of Competing Interest TH is the inventor of BK-SE36; TH, KJI, and TT are inventors of BK-SE36/CpG. NP and TH are both supported by a research fund from Nobelpharma Co., Ltd. (NPC), the clinical trial sponsor of Burkina Faso trials. These involvements did not influence the writing of this review and the decision to submit the article for publication.
(Copyright © 2023 Elsevier B.V. All rights reserved.)