Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice.

The Journal of Clinical Investigation
Alberto Pinzon-CharryMichael F Good

Abstract

Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4+ T cells, IFN-gamma, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell ...Continue Reading

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Citations

Nov 2, 2013·Trends in Parasitology·Danielle I StanisicMichael F Good
Aug 25, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Susanne H SheehySimon J Draper
Jan 11, 2011·Nature Medicine·Michael F Good, Christian Engwerda
Jul 10, 2013·The Journal of Experimental Medicine·Alberto Pinzon-CharryMichael F Good
Mar 23, 2012·Proceedings. Biological Sciences·Philip L F JohnsonRustom Antia
Aug 20, 2011·Science·Karen P Day, Freya J I Fowkes
Jul 19, 2013·The Journal of Clinical Investigation·Michael F GoodVirginia McPhun
Mar 25, 2014·Annual Review of Immunology·Peter D CromptonSusan K Pierce
Dec 3, 2010·The Journal of Clinical Investigation·Peter D CromptonLouis H Miller
Feb 18, 2011·Cellular and Molecular Life Sciences : CMLS·Michael F Good
Nov 16, 2012·Expert Review of Vaccines·Aiala SalvadorManoli Igartua
Dec 22, 2012·Expert Review of Vaccines·Alex Loukas, Michael F Good
Jan 9, 2016·Parasitology·Danielle I Stanisic, Michael F Good
Oct 3, 2015·Vaccine·Danielle I Stanisic, Michael F Good
Nov 6, 2015·Journal of Immunology Research·Ali N KamaliJosé M Bautista
Oct 30, 2010·Immunity·Michael F Good, Denise L Doolan
May 1, 2012·International Journal for Parasitology·Peter Liehl, Maria M Mota
Aug 22, 2016·Acta Biomaterialia·Ashwini Kumar GiddamMichael F Good
Mar 4, 2015·Infection and Immunity·Taiping LiuWenyue Xu
Nov 6, 2013·Parasite Immunology·J B de Souza
Feb 1, 2018·Expert Review of Vaccines·Michael F Good, Louis H Miller
Nov 12, 2019·Immunological Reviews·Michael F Good, Danielle I Stanisic
Apr 28, 2019·Nature Communications·Alexander D DouglasSimon J Draper
Sep 26, 2019·Immunological Reviews·Margaret E Feeney
Nov 26, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simon J DraperAdrian V S Hill
Apr 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sumi BiswasSimon J Draper
May 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Taiping LiuWenyue Xu
Apr 6, 2019·Frontiers in Immunology·Janna HeideJulian Schulze Zur Wiesch
Jan 13, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kylie R JamesAshraful Haque
Sep 17, 2019·European Journal of Medicinal Chemistry·Anudeep K NarulaLalit M Nainwal
Dec 22, 2017·Emerging Topics in Life Sciences·Michael F Good, Stephanie K Yanow
May 15, 2021·Cell Host & Microbe·Hanan A Al-NazalMichael F Good
May 18, 2021·Frontiers in Microbiology·Jingjing CaiWenyue Xu
Oct 20, 2018·Science Translational Medicine·Pamela M OdorizziMargaret E Feeney

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Methods Mentioned

BETA
ELISA
PMA
lavage

Software Mentioned

GraphPad Prism
CellQuest
CellQuest Pro
CBA

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