Viral Vector Vaccines for Liver-Stage Malaria

Malaria ◽  
2017 ◽  
pp. 157-169
Author(s):  
Cristina Fernández-Arias ◽  
Moriya Tsuji
Keyword(s):  
Viral Vector ◽  
Liver Stage

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

2009 ◽  
Vol 78 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Arturo Reyes-Sandoval ◽  
Tamara Berthoud ◽  
Nicola Alder ◽  
Loredana Siani ◽  
Sarah C. Gilbert ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Viral Vector ◽  
T Cell Responses ◽  
Adenoviral Vectors ◽  
Liver Stage ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Tnf Α

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.

scholarly journals Prime and target immunization protects against liver-stage malaria in mice

2018 ◽  
Vol 10 (460) ◽  
pp. eaap9128 ◽  
Author(s):  
Anita Gola ◽  
Daniel Silman ◽  
Adam A. Walters ◽  
Saranya Sridhar ◽  
Stefan Uderhardt ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Vectors ◽  
Viral Vector ◽  
Vaccination Strategy ◽  
Feasibility Trial ◽  
Effective Vaccine ◽  
Mosquito Vector ◽  
Erythrocytic Stage ◽  
Liver Stage ◽  
Circulating T Cells

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+ 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.

1440: Novel Non-Viral Vector Using Biodegradable Thermo-Sensitive Polymer (Regel®) in the Gene Therpy of Erectile Dysfunction

2004 ◽  
Vol 171 (4S) ◽  
pp. 379-379 ◽  
Author(s):  
Ji-Kan Ryu ◽  
Hwa-Yeon Shin ◽  
Minhyung Lee ◽  
Sun U. Song ◽  
Ki-Hak Moon ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Viral Vector

Viral Vector

2020 ◽  
Author(s):  
Keyword(s):  
Viral Vector

Half- Sandwich cyclopentadienylruthenium(II) Complexes: A New Antimalarial Chemotype

2020 ◽  
Author(s):  
Sofia Alexandra Milheiro ◽  
Joana Gonçalves ◽  
Ricardo Lopes ◽  
Margarida Madureira ◽  
Lis Lobo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Blood Stage ◽  
Nuclear Accumulation ◽  
Selective Absorption ◽  
Asexual Parasite ◽  
Single Digit ◽  
Liver Stage ◽  
Dual Stage ◽  
Fluorescent Compounds ◽  
Half Sandwich

<p><a>A small library of “half-sandwich” cyclopentadienylruthenium(II) compounds of general formula [(</a>η<sup>5</sup>-C<sub>5</sub>R<sub>5</sub>)Ru(PPh<sub>3</sub>)(N-N)][PF<sub>6</sub>], a scaffold hitherto unfeatured in the toolbox of antiplasmodials, was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2 and artemisinin-resistant IPC5202 <i>Plasmodium falciparum</i> strains, and the liver stage of <i>P. berghei</i>. The best performing compounds displayed dual-stage activity, with single-digit nM IC<sub>50</sub> values against blood stage malaria parasites, nM activity against liver stage parasites, and residual cytotoxicity against mammalian cells (HepG2, Huh7). Parasitic absorption/distribution of 7-nitrobenzoxadiazole-appended fluorescent compounds <b>Ru4</b> and <b>Ru5</b> was investigated by confocal fluorescence microscopy, revealing parasite-selective absorption in infected erythrocytes and nuclear accumulation of both compounds. The lead compound <b>Ru2</b> impaired asexual parasite differentiation, exhibiting fast parasiticidal activity against both ring and trophozoite stages of a synchronized <i>P. falciparum</i> 3D7 strain. These results point to cyclopentadienylruthenium(II) complexes as a highly promising chemotype for the development of dual-stage antiplasmodials.</p>

Enhanced Stability and Controlled Delivery of MOF Encapsulated Vaccines and Their Immunogenic Response In Vivo

2018 ◽  
Author(s):  
Michael Luzuriaga ◽  
Raymond P. Welch ◽  
Madushani Dharmawardana ◽  
Candace Benjamin ◽  
Shaobo Li ◽  
...  
Keyword(s):  
Viral Vector ◽  
Controlled Delivery ◽  
Conformational Structure ◽  
Spectroscopy Analysis ◽  
Zeolitic Imidazolate Framework ◽  
Structural Conformation ◽  
Depth Study ◽  
Viral Nanoparticle

<div><div><div><p>Vaccines have an innate tendency to lose their structural conformation upon environmental and chemical stressors. A loss in conformation reduces the therapeutic ability to prevent the spread of a pathogen. Herein, we report an in-depth study of zeolitic imidazolate framework-8 (ZIF-8) and its ability to provide protection for a model viral vector against dena- turing conditions. The immunoassay and spectroscopy analysis together demonstrate enhanced thermal and chemical stability to the conformational structure of the encapsulated viral nanoparticle. The long-term biological activity of this virus-ZIF composite was investigated in animal models to further elucidate the integrity of the encapsulated virus, the bio-safety, and immunogenicity of the overall composite. Additionally, histological analysis found no observable tissue damage in the skin or vital organs in mice, following multiple subcutaneous administrations. This study shows that ZIF-based protein composites are strong candidates for improved preservation of proteinaceous drugs, are biocompatible, and capable of controlling the release and adsorption of drugs in vivo.</p></div></div></div>

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