Signatures of malaria vaccine efficacy in ageing murine immune memory


Haussig, JM; Burgold, J; Hafalla, JCR; Matuschewski, K; Kooij, TWA; (2014) Signatures of malaria vaccine efficacy in ageing murine immune memory. Parasite immunology, 36 (5). pp. 199-206. ISSN 0141-9838 DOI: https://doi.org/10.1111/pim.12104

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Abstract

Malaria transmission occurs by mosquito bite. Thereafter, Plasmodium sporozoites specifically invade the liver, where they develop into thousands of merozoites that initiate blood-stage infection and clinical malaria. The pre-erythrocytic phase of a Plasmodium infection is the target of experimental whole-parasite vaccines against malaria. Repeated immunizations with high doses of live, metabolically active sporozoites can induce protracted protection against Plasmodium reinfection. Parasites lacking a Plasmodium-specific apicoplast protein, termed PALM, arrest very late during intrahepatic development just prior to liver merozoite release and can elicit sterile protection with two immunization doses only. In this report, we show in the robust Plasmodium berghei-C57BL/6 model that partial protection extends beyond 1year after the last immunization. In ageing mice, intracellular cytokine staining of Plasmodium peptide-stimulated intrahepatic CD8(+) T cells revealed elevated levels of interferon gamma in vaccinated mice. We conclude that antigen-specific T cells persist in the target organ and are critical signatures of lasting protection. Our data also support the notions that memory T-cell responses generated early in life remain largely intact well into old age and that murine Plasmodium vaccination and infection models are suitable to study the mechanisms of maintenance and efficiency of adaptive immunity during immunosenescence.

Item Type: Article
Keywords: Aging, immunology, Animals, CD8-Positive T-Lymphocytes, immunology, Female, Immunologic Memory, Interferon-gamma, immunology, Liver, immunology, parasitology, Malaria, immunology, parasitology, prevention & control, Malaria Vaccines, administration & dosage, Mice, Mice, Inbred C57BL, Parasitemia, immunology, Plasmodium berghei, immunology, Sporozoites, immunology
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 24495208
Web of Science ID: 333965700002
URI: http://researchonline.lshtm.ac.uk/id/eprint/1805400

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