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CD8 T cell independent immunity after single dose infection-treatment-vaccination (ITV) against Plasmodium yoelii
Journal article   Open access   Peer reviewed

CD8 T cell independent immunity after single dose infection-treatment-vaccination (ITV) against Plasmodium yoelii

Katherine L Doll, Noah S Butler and John T Harty
Vaccine, Vol.32(4), pp.483-491
01/16/2014
DOI: 10.1016/j.vaccine.2013.11.058
PMCID: PMC3923319
PMID: 24321740
url
https://doi.org/10.1016/j.vaccine.2013.11.058View
Published (Version of record) Open Access

Abstract

•P. yoelii ITV induces a larger CD8 T cell response than RAS vaccination in B6 mice.•Depletion of CD8 T cells does not abrogate ITV-induced sterilizing immunity.•ITV-induced immunity correlates with blood-stage resistance and antibodies. Sporozoite vaccination of both humans and rodents elicits potent anti-malarial immunity, but the dose of sporozoites and the number of immunizations required varies with vaccination approach. Here we examine the immunological basis for superior protection afforded from single-dose vaccination with virulent sporozoites administered under prophylatic chloroquine-cover, referred to as infection-treatment-vaccination (ITV), compared to the well-studied approach of administering radiation-attenuated Plasmodium sporozoites (RAS). Earlier rodent studies utilizing ITV and RAS vaccination suggested a major role of CD8 T cells in reducing liver parasite burden after sporozoite challenge in a BALB/c mouse model. Consistent with this, we find that in C57Bl/6 mice ITV elicits substantially higher parasite-specific CD8 T cell responses than RAS vaccination and enhances immunity against P. yoelii infection. However, we show ITV-induced CD8 T cells are not necessary for protection following liver-stage sporozoite or blood-stage parasite challenge. Mechanistically, we found protection afforded from single-dose ITV is associated with low grade, transient parasitemia shortly following cessation of chloroquine treatment and generation of potent antibody responses to blood-stage parasites. Collectively, our data show the mechanistic basis for enhanced protective immunity against P. yoelli elicited by ITV in highly susceptible C57Bl/6 mice is independent of CD8 T cells. These studies may be relevant in understanding the potent immunity observed with ITV in humans.
Subpatent infection Antibodies Plasmodium infections Vaccination CD8 T cells

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