A guide to investigating immune responses elicited by whole‐sporozoite pre‐erythrocytic vaccines against malaria

• Published in: The FEBS journal 2022-06, Vol.289 (12), p.3335-3359
• Main Authors: Moita, Diana, Nunes‐Cabaço, Helena, Mendes, António M., Prudêncio, Miguel
• Format: Article
• Language: English
• Subjects: antibodies; cellular responses; Clinical trials; controlled human malaria infection; Genetic modification; humoral responses; Immune response (cell-mediated); Immune response (humoral); immunity; Immunization; Immunogenicity; liver; lymphocytes; Malaria; P. falciparum; Parasites; Plasmodium; Radiation; Sporozoites; vaccination; Vaccines; Vector-borne diseases
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.16016

In the last few decades, considerable efforts have been made toward the development of efficient vaccines against malaria. Whole‐sporozoite (Wsp) vaccines, which induce efficient immune responses against the pre‐erythrocytic (PE) stages (sporozoites and liver forms) of Plasmodium parasites, the causative agents of malaria, are among the most promising immunization strategies tested until present. Several Wsp PE vaccination approaches are currently under evaluation in the clinic, including radiation‐ or genetically‐attenuated Plasmodium sporozoites, live parasites combined with chemoprophylaxis, or genetically modified rodent Plasmodium parasites. In addition to the assessment of their protective efficacy, clinical trials of Wsp PE vaccine candidates inevitably involve the thorough investigation of the immune responses elicited by vaccination, as well as the identification of correlates of protection. Here, we review the main methodologies employed to dissect the humoral and cellular immune responses observed in the context of Wsp PE vaccine clinical trials and discuss future strategies to further deepen the knowledge generated by these studies, providing a toolbox for the in‐depth analysis of vaccine‐induced immunogenicity. Whole‐sporozoite (Wsp) vaccines, employing attenuated malaria parasites, are among the most promising candidates for vaccination against this devastating disease. The evaluation of Wsp vaccines in human volunteers is essential not only to assess their protective efficacy, but also to investigate the immunity elicited by vaccination and identify correlates of protection. We review current and future methodologies to evaluate the immune responses triggered by Wsp vaccines in the clinic.