Research on Malaria Immunology in Animal Models

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against (re)emerging and Tropical Infections Diseases".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 8688

Special Issue Editors

Department of Pathology, The University of Utah, Salt Lake City, UT 84112, USA
Interests: malaria; pathogenesis; immunology; co-infection; mouse models; T cells
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA
Interests: antibody secreting cells; malaria; pathogenesis; immunology; non-human primate models; B cells

Special Issue Information

Malaria remains a significant cause of morbidity and mortality throughout the world. Although chemotherapeutic strategies to target malaria are effective, long-term protection against malaria can only be realized by the advent of a successful vaccine. The development of a vaccine requires an in-depth knowledge of how the Plasmodium parasites that cause malaria interact with the immune system. Correlating patient immune responses with the infection phenotype in malaria-endemic areas will not achieve this goal in isolation. The implementation of animal models of malaria is necessary to dissect how the immune system responds to Plasmodium, controls the invading parasites and causes pathology in organs where parasites sequester. 

Anti-parasite immunity can be achieved over time with constant exposure to infection in people living in endemic areas. However, this response is not sterilizing and therefore parasites still circulate. Resistance to the development of malarial symptoms despite the presence of Plasmodium infection, often referred to as “clinical immunity”, is also a key player in malaria immunobiology. Both the innate and adaptive arms of the immune system play a role in these processes, but many of the immunological mechanisms mediating anti-malarial immunity are still poorly understood. 

This Special Issue will focus on new and established animal models of Plasmodium infection that can be used to interrogate the immunobiology of malaria. The goal is to provide a collection of articles that will focus on the recent scientific and technical progress made in this field. Based on your extensive knowledge and experience, we invite you to contribute with an original report, original observation or review, to highlight (i) new animal models of malaria, (ii) new insights into the immunobiology of malaria using animal models and (iii) recent advances in novel prophylactic and therapeutic vaccines in animal models of malaria.

Dr. Tracey J. Lamb
Dr. Chester J. Joyner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • malaria
  • Plasmodium infection
  • non-human primate models
  • mouse models
  • immunology
  • vaccines
  • innate immunity
  • adaptive immunity
  • anti-parasite immunity
  • clinical immunity

Published Papers (3 papers)

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Research

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22 pages, 2470 KiB  
Article
Vaccination Accelerates Liver-Intrinsic Expression of Megakaryocyte-Related Genes in Response to Blood-Stage Malaria
by Frank Wunderlich, Denis Delic, Daniela Gerovska and Marcos J. Araúzo-Bravo
Vaccines 2022, 10(2), 287; https://doi.org/10.3390/vaccines10020287 - 14 Feb 2022
Cited by 1 | Viewed by 1615
Abstract
Erythropoiesis and megakaryo-/thrombopoiesis occur in the bone marrow proceeding from common, even bipotent, progenitor cells. Recently, we have shown that protective vaccination accelerates extramedullary hepatic erythroblastosis in response to blood-stage malaria of Plasmodium chabaudi. Here, we investigated whether protective vaccination also accelerates extramedullary [...] Read more.
Erythropoiesis and megakaryo-/thrombopoiesis occur in the bone marrow proceeding from common, even bipotent, progenitor cells. Recently, we have shown that protective vaccination accelerates extramedullary hepatic erythroblastosis in response to blood-stage malaria of Plasmodium chabaudi. Here, we investigated whether protective vaccination also accelerates extramedullary hepatic megakaryo-/thrombopoiesis. Female Balb/c mice were twice vaccinated with a non-infectious vaccine before infecting with 106 P. chabaudi-parasitized erythrocytes. Using gene expression microarrays and quantitative real-time PCR, transcripts of genes known to be expressed in the bone marrow by cells of the megakaryo-/thrombocytic lineage were compared in livers of vaccination-protected and unprotected mice on days 0, 1, 4, 8, and 11 p.i. Livers of vaccination-protected mice responded with expression of megakaryo-/thrombocytic genes faster to P. chabaudi than those of unvaccinated mice, evidenced at early patency on day 4 p.i., when livers exhibited significantly higher levels of malaria-induced transcripts of the genes Selp and Pdgfb (p-values < 0.0001), Gp5 (p-value < 0.001), and Fli1, Runx1, Myb, Mpl, Gp1ba, Gp1bb, Gp6, Gp9, Pf4, and Clec1b (p-values < 0.01). Together with additionally analyzed genes known to be related to megakaryopoiesis, our data suggest that protective vaccination accelerates liver-intrinsic megakaryo-/thrombopoiesis in response to blood-stage malaria that presumably contributes to vaccination-induced survival of otherwise lethal blood-stage malaria. Full article
(This article belongs to the Special Issue Research on Malaria Immunology in Animal Models)
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15 pages, 2464 KiB  
Article
Design of Alphavirus Virus-Like Particles Presenting Circumsporozoite Junctional Epitopes That Elicit Protection against Malaria
by Joseph R. Francica, Wei Shi, Gwo-Yu Chuang, Steven J. Chen, Lais Da Silva Pereira, S. Katie Farney, Barbara J. Flynn, Li Ou, Tyler Stephens, Yaroslav Tsybovsky, Lawrence T. Wang, Alexander Anderson, Zoltan Beck, Marlon Dillon, Azza H. Idris, Nicholas Hurlburt, Tracy Liu, Baoshan Zhang, Carl R. Alving, Gary R. Matyas, Marie Pancera, John R. Mascola, Peter D. Kwong and Robert A. Sederadd Show full author list remove Hide full author list
Vaccines 2021, 9(3), 272; https://doi.org/10.3390/vaccines9030272 - 18 Mar 2021
Cited by 13 | Viewed by 2956
Abstract
The most advanced malaria vaccine, RTS,S, includes the central repeat and C-terminal domains of the Plasmodium falciparum circumsporozoite protein (PfCSP). We have recently isolated human antibodies that target the junctional region between the N-terminal and repeat domains that are not included in RTS,S. [...] Read more.
The most advanced malaria vaccine, RTS,S, includes the central repeat and C-terminal domains of the Plasmodium falciparum circumsporozoite protein (PfCSP). We have recently isolated human antibodies that target the junctional region between the N-terminal and repeat domains that are not included in RTS,S. Due to the fact that these antibodies protect against malaria challenge in mice, their epitopes could be effective vaccine targets. Here, we developed immunogens displaying PfCSP junctional epitopes by genetic fusion to either the N-terminus or B domain loop of the E2 protein from chikungunya (CHIK) alphavirus and produced CHIK virus-like particles (CHIK-VLPs). The structural integrity of these junctional-epitope–CHIK-VLP immunogens was confirmed by negative-stain electron microscopy. Immunization of these CHIK-VLP immunogens reduced parasite liver load by up to 95% in a mouse model of malaria infection and elicited better protection than when displayed on keyhole limpet hemocyanin, a commonly used immunogenic carrier. Protection correlated with PfCSP serum titer. Of note, different junctional sequences elicited qualitatively different reactivities to overlapping PfCSP peptides. Overall, these results show that the junctional epitopes of PfCSP can induce protective responses when displayed on CHIK-VLP immunogens and provide a basis for the development of a next generation malaria vaccine to expand the breadth of anti-PfCSP immunity. Full article
(This article belongs to the Special Issue Research on Malaria Immunology in Animal Models)
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Review

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41 pages, 1701 KiB  
Review
Mouse Models for Unravelling Immunology of Blood Stage Malaria
by Adesola C. Olatunde, Douglas H. Cornwall, Marshall Roedel and Tracey J. Lamb
Vaccines 2022, 10(9), 1525; https://doi.org/10.3390/vaccines10091525 - 14 Sep 2022
Cited by 5 | Viewed by 3510
Abstract
Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. [...] Read more.
Malaria comprises a spectrum of disease syndromes and the immune system is a major participant in malarial disease. This is particularly true in relation to the immune responses elicited against blood stages of Plasmodium-parasites that are responsible for the pathogenesis of infection. Mouse models of malaria are commonly used to dissect the immune mechanisms underlying disease. While no single mouse model of Plasmodium infection completely recapitulates all the features of malaria in humans, collectively the existing models are invaluable for defining the events that lead to the immunopathogenesis of malaria. Here we review the different mouse models of Plasmodium infection that are available, and highlight some of the main contributions these models have made with regards to identifying immune mechanisms of parasite control and the immunopathogenesis of malaria. Full article
(This article belongs to the Special Issue Research on Malaria Immunology in Animal Models)
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