{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:15:34Z","timestamp":1784888134880,"version":"3.55.0"},"reference-count":21,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2012,1,5]],"date-time":"2012-01-05T00:00:00Z","timestamp":1325721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hydrodynamic tail vein (HTV) delivery is a simple and rapid tail vein injection method of a high volume of naked plasmid DNA resulting in high levels of foreign gene expression in organs, especially the liver. Compared to other organs, HTV delivery results in more than a 1000-fold higher transgene expression in liver. After being bitten by malaria-infected mosquitoes, malaria parasites transiently infect the host liver and form the liver stages. The liver stages are known to be the key target for CD8+ T cells that mediate protective anti-malaria immunity in an animal model. Therefore, in this study, we utilized the HTV delivery technique as a tool to determine the in vivo cytotoxic effect of malaria antigen-specific CD8+ T cells. Two weeks after mice were immunized with recombinant adenoviruses expressing malarial antigens, the immunized mice as well as na\u00efve mice were challenged by HTV delivery of naked plasmid DNA co-encoding respective antigen together with luciferase using dual promoters. Three days after the HTV challenge, non-invasive whole-body bioluminescent imaging was performed. The images demonstrate in vivo activity of CD8+ T cells against malaria antigen-expressing cells in liver.<\/jats:p>","DOI":"10.3390\/biom2010023","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T04:04:03Z","timestamp":1325822643000},"page":"23-33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A New Method to Determine Antigen-Specific CD8+ T Cell Activity in Vivo by Hydrodynamic Injection"],"prefix":"10.3390","volume":"2","author":[{"given":"Urvashi","family":"Rai","sequence":"first","affiliation":[{"name":"HIV and Malaria Vaccine Program, The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"HIV and Malaria Vaccine Program, The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Mishra","sequence":"additional","affiliation":[{"name":"Michael Heidelberger Division, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangming","family":"Li","sequence":"additional","affiliation":[{"name":"HIV and Malaria Vaccine Program, The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Shiratsuchi","sequence":"additional","affiliation":[{"name":"HIV and Malaria Vaccine Program, The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moriya","family":"Tsuji","sequence":"additional","affiliation":[{"name":"HIV and Malaria Vaccine Program, The Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/330664a0","article-title":"\u03b3 Interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites","volume":"330","author":"Schofield","year":"1987","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1073\/pnas.85.2.573","article-title":"CD8+ T cells (cytotoxic\/suppressors) are required for protection in mice immunized with malaria sporozoites","volume":"85","author":"Weiss","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/intimm\/3.6.579","article-title":"CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria","volume":"3","author":"Rodrigues","year":"1991","journal-title":"Int. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/341323a0","article-title":"Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria","volume":"341","author":"Romero","year":"1989","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.4049\/jimmunol.158.3.1268","article-title":"Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria","volume":"158","author":"Rodrigues","year":"1997","journal-title":"J. Immunol."},{"key":"ref_6","first-page":"397","article-title":"Pre-erythrocytic malaria vaccine: Mechanisms of protective immunity and human vaccine trials","volume":"41","author":"Nardin","year":"1999","journal-title":"Parassitologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","article-title":"RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S\/AS01 malaria vaccine in African children","volume":"365","author":"Agnandji","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9952","DOI":"10.1073\/pnas.1633254100","article-title":"Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data","volume":"100","author":"Doolan","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.1016\/j.vaccine.2011.06.053","article-title":"Cellular and humoral immune effector mechanisms required for sterile protection against sporozoite challenge induced with the novel malaria vaccine candidate CelTOS","volume":"29","author":"Legler","year":"2011","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1690918","article-title":"Direct gene transfer into mouse muscle in vivo","volume":"247","author":"Wolff","year":"1990","journal-title":"Science"},{"key":"ref_11","first-page":"593","article-title":"Naked DNA delivered intraportally expresses efficiently in hepatocytes","volume":"3","author":"Budker","year":"1996","journal-title":"Gene Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1089\/hum.1997.8.15-1763","article-title":"Expression of naked plasmid DNA injected into the afferent and efferent vessels of rodent and dog livers","volume":"8","author":"Zhang","year":"1997","journal-title":"Hum. Gene Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/sj.gt.3300947","article-title":"Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA","volume":"6","author":"Liu","year":"1999","journal-title":"Gene Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1089\/10430349950017734","article-title":"High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA","volume":"10","author":"Zhang","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7335","DOI":"10.1016\/j.vaccine.2011.07.081","article-title":"Identification of non-CSP antigens bearing CD8 epitopes in mice immunized with irradiated sporozoites","volume":"29","author":"Mishra","year":"2011","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1172\/JCI39812","article-title":"Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice","volume":"120","author":"Shiratsuchi","year":"2010","journal-title":"J. Clin. Invest."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1038\/sj.mt.6300314","article-title":"Hydrodynamic gene delivery: Its principles and applications","volume":"15","author":"Suda","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/sj.gt.3302210","article-title":"Hydroporation as the mechanism of hydrodynamic delivery","volume":"11","author":"Zhang","year":"2004","journal-title":"Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S1874-5326(00)80012-5","article-title":"Immunopathogenesis of Hepatitis C","volume":"Volume 2","author":"Liang","year":"2000","journal-title":"Hepatitis C (Biomedical Research Reports)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/326881a0","article-title":"Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2","volume":"326","author":"Gotch","year":"1987","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1084\/jem.168.3.1163","article-title":"Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus","volume":"168","author":"Cannon","year":"1988","journal-title":"J. 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