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Prime and target immunization protects against liver-stage malaria in mice.
- Source :
-
Science translational medicine [Sci Transl Med] 2018 Sep 26; Vol. 10 (460). - Publication Year :
- 2018
-
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 <superscript>+</superscript> 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.<br /> (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Animals
Biomarkers metabolism
CD8-Positive T-Lymphocytes immunology
Genetic Vectors administration & dosage
Hepatocytes immunology
Hepatocytes parasitology
Humans
Injections, Intravenous
Malaria, Falciparum pathology
Mice, Inbred C57BL
Nanoparticles chemistry
Ovalbumin immunology
Plasmodium berghei physiology
Plasmodium falciparum growth & development
Polylactic Acid-Polyglycolic Acid Copolymer chemistry
Sporozoites physiology
Immunization
Life Cycle Stages
Liver parasitology
Malaria, Falciparum immunology
Malaria, Falciparum prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 10
- Issue :
- 460
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30257955
- Full Text :
- https://doi.org/10.1126/scitranslmed.aap9128