Development of Plasmodium‐specific liver‐resident memory CD8+ T cells after heat‐killed sporozoite immunization in mice

• Published in: European journal of immunology 2021-05, Vol.51 (5), p.1153-1165
• Main Authors: Ghilas, Sonia, Enders, Matthias H., May, Rose, Holz, Lauren E., Fernandez‐Ruiz, Daniel, Cozijnsen, Anton, Mollard, Vanessa, Cockburn, Ian A., McFadden, Geoffrey I., Heath, William R., Beattie, Lynette
• Format: Article
• Language: English
• Subjects: CD8 antigen; CD8+ T cells; Galactosylceramide; Heat treatments; Hepatocytes; Immunological memory; Injection; Liver; Liver diseases; Lymphocytes; Lymphocytes T; Malaria; Memory cells; Plasmodium; Spleen; Sporozoites; T cell receptors; Transgenic mice; Vaccination
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202048757

Malaria remains a major cause of mortality in the world and an efficient vaccine is the best chance of reducing the disease burden. Vaccination strategies for the liver stage of disease that utilise injection of live radiation‐attenuated sporozoites (RAS) confer sterile immunity, which is mediated by CD8+ memory T cells, with liver‐resident memory T cells (TRM) being particularly important. We have previously described a TCR transgenic mouse, termed PbT‐I, where all CD8+ T cells recognize a specific peptide from Plasmodium. PbT‐I form liver TRM cells upon RAS injection and are capable of protecting mice against challenge infection. Here, we utilize this transgenic system to examine whether nonliving sporozoites, killed by heat treatment (HKS), could trigger the development of Plasmodium‐specific liver TRM cells. We found that HKS vaccination induced the formation of memory CD8+ T cells in the spleen and liver, and importantly, liver TRM cells were fewer in number than that induced by RAS. Crucially, we showed the number of TRM cells was significantly higher when HKS were combined with the glycolipid α‐galactosylceramide as an adjuvant. In the future, this work could lead to development of an antimalaria vaccination strategy that does not require live sporozoites, providing greater utility. Vaccination with radiation‐attenuated Plasmodium sporozoites is known to induce liver‐resident memory CD8+ T cells (TRM) that confer sterile protection. We show that immunization with heat‐killed Plasmodium sporozoites also trigger liver TRM formation, but their numbers are suboptimal for sterile protection, even when enhanced by the adjuvant α‐galactosylceramide.