Prime and target immunization protects against liver-stage malaria in mice

Gola A, Silman D, Walters AA, Sridhar S, Uderhardt S, Saman AM, Halbroth BR, Bellamy D, Bowyer G, Powlson J, Baker M, Venkatraman N, Poulton I, Berrie E, Roberts R, Lawrie AM, Angus B, Khan SM, Janse CJ, Ewer KJ, Germain RN, Spencer AJ, Hill AVS (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Science Translational Medicine American Association for the Advancement of Science

Book Volume: 10

Article Number: eaap9128

Journal Issue: 460

DOI: 10.1126/scitranslmed.aap9128

Abstract

Despite recent advances in treatment and vector control, malaria is still a leading cause of death, emphasizing the need for an effective vaccine. The malaria life cycle can be subdivided into three stages: the invasion and growth within liver hepatocytes (pre-erythrocytic stage), the blood stage (erythrocytic stage), and, finally, the sexual stage (occurring within the mosquito vector). Antigen (Ag)-specific CD8+ T cells are effectively induced by heterologous prime-boost viral vector immunization and known to correlate with liver-stage protection. However, liver-stage malaria vaccines have struggled to generate and maintain the high numbers of Plasmodium-specific circulating T cells necessary to confer sterile protection. We describe an alternative "prime and target" vaccination strategy aimed specifically at inducing high numbers of tissue-resident memory T cells present in the liver at the time of hepatic infection. This approach bypasses the need for very high numbers of circulating T cells and markedly increases the efficacy of subunit immunization against liver-stage malaria with clinically relevant Ags and clinically tested viral vectors in murine challenge models. Translation to clinical use has begun, with encouraging results from a pilot safety and feasibility trial of intravenous chimpanzee adenovirus vaccination in humans. This work highlights the value of a prime-target approach for immunization against malaria and suggests that this strategy may represent a more general approach for prophylaxis or immunotherapy of other liver infections and diseases.

Authors with CRIS profile

Stefan Uderhardt

Involved external institutions

University of Oxford GB United Kingdom (GB) Leiden University NL Netherlands (NL) US National Institutes of Health (NIH) US United States (USA) (US)

How to cite

APA:

Gola, A., Silman, D., Walters, A.A., Sridhar, S., Uderhardt, S., Saman, A.M.,... Hill, A.V.S. (2018). Prime and target immunization protects against liver-stage malaria in mice. Science Translational Medicine, 10(460). https://doi.org/10.1126/scitranslmed.aap9128

MLA:

Gola, Anita, et al. "Prime and target immunization protects against liver-stage malaria in mice." Science Translational Medicine 10.460 (2018).

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