NDLI: Prime-Boost Immunization with Adenoviral and Modified Vaccinia Virus Ankara Vectors Enhances the Durability and Polyfunctionality of Protective Malaria CD8+ T-Cell Responses▿ †

Content Provider	PubMed Central
Author	Arturo, Reyes-sandoval Berthoud, Tamara Alder, Nicola Siani, Loredana Gilbert, Sarah C. Nicosia, Alfredo Colloca, Stefano Cortese, Riccardo Hill, Adrian V. S.
Copyright Year	2010
Abstract	Protection against liver-stage malaria relies on the induction of high frequencies of antigen-specific CD8+ T cells. We have previously reported high protective levels against mouse malaria, albeit short-lived, by a single vaccination with adenoviral vectors coding for a liver-stage antigen (ME.TRAP). Here, we report that prime-boost regimens using modified vaccinia virus Ankara (MVA) and adenoviral vectors encoding ME.TRAP can enhance both short- and long-term sterile protection against malaria. Protection persisted for at least 6 months when simian adenoviruses AdCh63 and AdC9 were used as priming vectors. Kinetic analysis showed that the MVA boost made the adenoviral-primed T cells markedly more polyfunctional, with the number of gamma interferon (INF-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) triple-positive and INF-γ and TNF-α double-positive cells increasing over time, while INF-γ single-positive cells declined with time. However, IFN-γ production prevailed as the main immune correlate of protection, while neither an increase of polyfunctionality nor a high integrated mean fluorescence intensity (iMFI) correlated with protection. These data highlight the ability of optimized viral vector prime-boost regimens to generate more protective and sustained CD8+ T-cell responses, and our results encourage a more nuanced assessment of the importance of inducing polyfunctional CD8+ T cells by vaccination.
Related Links	http://dx.doi.org/10.1128/iai.00740-09
Ending Page	153
Page Count	9
Starting Page	145
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	1
Volume Number	78
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2010-01-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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