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Infection and Immunity Apr 2020Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including... (Review)
Review
Efficient delivery of antigenic cargo to trigger protective immune responses is critical to the success of vaccination. Genetically engineered microorganisms, including virus, bacteria, and protozoa, can be modified to carry and deliver heterologous antigens to the host immune system. The biological vectors can induce a broad range of immune responses and enhance heterologous antigen-specific immunological outcomes. The protozoan genus is widespread in domestic animals, causing serious coccidiosis. parasites with strong immunogenicity are potent coccidiosis vaccine candidates and offer a valuable model of live vaccines against infectious diseases in animals. parasites can also function as a vaccine vector. Herein, we review recent advances in design and application of recombinant as a vaccine vector, which has been a topic of ongoing research in our laboratory. By recapitulating the establishment of an transfection platform and its application, it will help lay the foundation for the future development of effective parasite-based vaccine delivery vectors and beyond.
Topics: Animals; Antigens, Protozoan; Coccidiosis; Eimeria; Humans; Microorganisms, Genetically-Modified; Protozoan Vaccines; Vaccination; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 32094255
DOI: 10.1128/IAI.00861-19 -
Seminars in Immunopathology May 2015Trypanosoma cruzi infection and Chagas disease remains among the most neglected of the neglected tropical diseases. Despite this, studies of the immune response to T.... (Review)
Review
Trypanosoma cruzi infection and Chagas disease remains among the most neglected of the neglected tropical diseases. Despite this, studies of the immune response to T. cruzi have provided new insights in immunology and guidance for approaches for prevention and treatment of the disease. T. cruzi represents one of the very best systems in which to study CD8(+) T cell biology; mice, dogs, and primates (and many other mammals) are all natural hosts for this parasite, the robust T cell responses generated in these hosts can be readily monitored using the full range of cutting edge techniques, and the parasite can be easily modified to express (or not) a variety of tags, reporters, immune enhances, and endogenous or model antigens. The infection in most hosts is characterized by vigorous and largely effective immune responses, including CD8(+) T cells capable of controlling T. cruzi at the level of the infected host cells. However, this immune control is only partially effective and most hosts maintain a low level infection for life. This review addresses the interplay of highly effective CD8(+) T cell responses with elaborate pathogen immune evasion mechanisms, including the generation and simultaneous expression of highly variant CD8(+) T cell targets and a host cell invasion mechanisms that largely eludes innate immune detection.
Topics: Animals; CD8-Positive T-Lymphocytes; Chagas Disease; Epitopes, T-Lymphocyte; Host-Parasite Interactions; Humans; Immune Evasion; Lymphocyte Activation; Pathogen-Associated Molecular Pattern Molecules; Protozoan Vaccines; T-Cell Antigen Receptor Specificity; Trypanosoma cruzi
PubMed: 25921214
DOI: 10.1007/s00281-015-0481-9 -
Experimental Parasitology Sep 2020Despite decades of investigation to clarify protective mechanisms of anticoccidial responses, one crucial field is neglected, that is, protective memory responses in... (Review)
Review
Despite decades of investigation to clarify protective mechanisms of anticoccidial responses, one crucial field is neglected, that is, protective memory responses in primed birds. Protective memory immunity is critical for host resistance to reinfection and is the basis of modern vaccinology, especially in developing successful subunit vaccines. There are important differences between the immune responses induced by infections and antigens delivered either as killed, recombinant proteins or as live, replicating vector vaccines or as DNA vaccines. Animals immunized with these vaccines may fail to develop protective memory immunity, and is still naïve to Eimeria infection. This may explain why limited success is achieved in developing next-generation anticoccidial vaccines. In this review, we try to decipher the protective memory responses against Eimeria infection, assess immune responses elicited by various anticoccidial vaccine candidates, and propose possible approaches to develop rational vaccines that can induce a protective memory response to chicken coccidiosis.
Topics: Animals; Chickens; Coccidiosis; Eimeria; Immunologic Memory; Intestines; Poultry Diseases; Protozoan Vaccines; Recurrence; Vaccination; Vaccines, Subunit
PubMed: 32615133
DOI: 10.1016/j.exppara.2020.107945 -
Medical Science Monitor : International... Jan 2023There is hope that 2023 could bring regulatory approval, licensing, and implementation programs for safe and effective adjuvanted vaccines to prevent malaria. Clinical...
There is hope that 2023 could bring regulatory approval, licensing, and implementation programs for safe and effective adjuvanted vaccines to prevent malaria. Clinical trials involving the two leading adjuvanted malaria vaccines directed to the Plasmodium falciparum circumsporozoite protein (PfCSP) are ongoing. These vaccines are RTS,S/ASO1 (Mosquirix®) and R21/Matrix-M™ (R21/MM). This year, the World Health Organization (WHO) updated its strategy to eradicate malaria by 2030. The hope is that major advances in global health security from effective malarial vaccines could reduce morbidity and save the lives of millions of people living in malaria-endemic countries to achieve the goals recommended by the WHO. This Editorial aims to give an update on recent findings from key clinical trials on the safety and efficacy of RTS,S/ASO1 and R21/MM malaria vaccines and to provide an insight into the importance of key ongoing clinical trials that will report in early 2023.
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Malaria; Protozoan Proteins; World Health Organization
PubMed: 36587274
DOI: 10.12659/MSM.939357 -
Virulence Dec 2020Individuals growing up in malaria endemic areas gradually develop protection against clinical malaria and passive transfer experiments in humans have demonstrated that... (Review)
Review
Individuals growing up in malaria endemic areas gradually develop protection against clinical malaria and passive transfer experiments in humans have demonstrated that this protection is mediated in part by protective antibodies. However, neither the target antigens, specific effector mechanisms, nor the role of continual parasite exposure have been elucidated, which complicates vaccine development. Progress has been made in defining the innate signaling pathways activated by parasite components, including DNA, RNA, hemozoin, and phospholipids, which initiate the immune response and will be the focus of this review. The challenge that remains within the field is to understand the role of these early responses in the development of protective adaptive responses that clear iRBC and block merozoite invasion so that optimal vaccines and therapeutics may be produced.
Topics: Adaptive Immunity; Animals; Antigens, Protozoan; Antimalarials; Dendritic Cells; Erythrocytes; Hemeproteins; Humans; Immunity; Killer Cells, Natural; Life Cycle Stages; Malaria; Malaria, Falciparum; Merozoites; Parasites; Phospholipids; Pigments, Biological; Plasmodium falciparum; Protozoan Proteins; Protozoan Vaccines
PubMed: 31900030
DOI: 10.1080/21505594.2019.1708053 -
The Korean Journal of Parasitology Dec 2014Toxoplasmosis is an opportunistic infection caused by the protozoan parasite Toxoplasma gondii. T. gondii is widespread globally and causes severe diseases in... (Review)
Review
Toxoplasmosis is an opportunistic infection caused by the protozoan parasite Toxoplasma gondii. T. gondii is widespread globally and causes severe diseases in individuals with impaired immune defences as well as congenitally infected infants. The high prevalence rate in some parts of the world such as South America and Africa, coupled with the current drug treatments that trigger hypersensitivity reactions, makes the development of immunotherapeutics intervention a highly important research priority. Immunotherapeutics strategies could either be a vaccine which would confer a pre-emptive immunity to infection, or passive immunization in cases of disease recrudescence or recurrent clinical diseases. As the severity of clinical manifestations is often greater in developing nations, the development of well-tolerated and safe immunotherapeutics becomes not only a scientific pursuit, but a humanitarian enterprise. In the last few years, much progress has been made in vaccine research with new antigens, novel adjuvants, and innovative vaccine delivery such as nanoparticles and antigen encapsulations. A literature search over the past 5 years showed that most experimental studies were focused on DNA vaccination at 52%, followed by protein vaccination which formed 36% of the studies, live attenuated vaccinations at 9%, and heterologous vaccination at 3%; while there were few on passive immunization. Recent progress in studies on vaccination, passive immunization, as well as insights gained from these immunotherapeutics is highlighted in this review.
Topics: Drug Discovery; Global Health; Humans; Immunization; Immunotherapy; Protozoan Vaccines; Toxoplasma; Toxoplasmosis
PubMed: 25548409
DOI: 10.3347/kjp.2014.52.6.581 -
Expert Review of Vaccines Nov 2021Pathogenesis of Chagas disease (CD) caused by involves chronic oxidative and inflammatory stress. In this review, we discuss the research efforts in therapeutic vaccine... (Review)
Review
INTRODUCTION
Pathogenesis of Chagas disease (CD) caused by involves chronic oxidative and inflammatory stress. In this review, we discuss the research efforts in therapeutic vaccine development to date and the potential challenges imposed by oxidative stress in achieving an efficient therapeutic vaccine against CD.
AREAS COVERED
This review covers the immune and nonimmune mechanisms of reactive oxygen species production and immune response patterns during in CD. A discussion on immunotherapy development efforts, the efficacy of antigen-based immune therapies against , and the role of antioxidants as adjuvants is discussed to provide promising insights to developing future treatment strategies against CD.
EXPERT OPINION
Administration of therapeutic vaccines can be a good option to confront persistent parasitemia in CD by achieving a rapid, short-lived stimulation of type 1 cell-mediated immunity. At the same time, adjunct therapies could play a critical role in the preservation of mitochondrial metabolism and cardiac muscle contractility in CD. We propose combined therapy with antigen-based vaccine and small molecules to control the pathological oxidative insult would be effective in the conservation of cardiac structure and function in CD.
Topics: Chagas Disease; Humans; Oxidative Stress; Protozoan Vaccines; Trypanosoma cruzi; Vaccine Development
PubMed: 34406892
DOI: 10.1080/14760584.2021.1969230 -
Frontiers in Immunology 2023, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective...
, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from , was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti--specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce -specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after challenge ( 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively ( 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against infection.
Topics: Animals; Mice; Mice, Inbred BALB C; Protozoan Proteins; Protozoan Vaccines; Toxoplasmosis; Immunization; Immunoglobulin G
PubMed: 37122740
DOI: 10.3389/fimmu.2023.1161507 -
Journal of Vector Borne Diseases 2023Leishmaniasis is a parasitic disease with different clinical forms caused by protozoan parasites of the genus Leishmania and transmitted by the bite of an infected... (Review)
Review
Leishmaniasis is a parasitic disease with different clinical forms caused by protozoan parasites of the genus Leishmania and transmitted by the bite of an infected female sandfly. According to the World Health Organization (WHO), it is the second most common parasitic disease after malaria and it is known that approximately 350 million people are at risk. The disease manifests itself in different clinical forms. In addition to asymptomatic cases, cutaneous leishmaniasis (CL), which creates large lesions on the skin, and visceral leishmaniasis (VL), which causes death if not treated, especially affecting the abdominal organs, are two important clinical forms. When the studies were examined, it was seen that a clinically used vaccine against any form of human leishmaniasis has not been developed yet. In some studies, it was stated that the lack of appropriate adjuvant was responsible for the failure to develop an effective Leishmania vaccine. We can say that strong adjuvants are needed to achieve successful vaccines. In this article, adjuvants and adjuvant candidates used in vaccine studies against leishmaniasis are discussed.
Topics: Female; Humans; Leishmaniasis Vaccines; Adjuvants, Immunologic; Leishmaniasis, Visceral; Leishmania; Leishmaniasis, Cutaneous
PubMed: 37417162
DOI: 10.4103/0972-9062.361179 -
Parasite Immunology Dec 2016Despite having different cell tropism, the pathogenesis and immunobiology of the diseases caused by Theileria parva and Theileria annulata are remarkably similar. Live... (Review)
Review
Despite having different cell tropism, the pathogenesis and immunobiology of the diseases caused by Theileria parva and Theileria annulata are remarkably similar. Live vaccines have been available for both parasites for over 40 years, but although they provide strong protection, practical disadvantages have limited their widespread application. Efforts to develop alternative vaccines using defined parasite antigens have focused on the sporozoite and intracellular schizont stages of the parasites. Experimental vaccination studies using viral vectors expressing T. parva schizont antigens and T. parva and T. annulata sporozoite antigens incorporated in adjuvant have, in each case, demonstrated protection against parasite challenge in a proportion of vaccinated animals. Current work is investigating alternative antigen delivery systems in an attempt to improve the levels of protection. The genome architecture and protein-coding capacity of T. parva and T. annulata are remarkably similar. The major sporozoite surface antigen in both species and most of the schizont antigens are encoded by orthologous genes. The former have been shown to induce species cross-reactive neutralizing antibodies, and comparison of the schizont antigen orthologues has demonstrated that some of them display high levels of sequence conservation. Hence, advances in development of subunit vaccines against one parasite species are likely to be readily applicable to the other.
Topics: Animals; Antibodies, Neutralizing; Antigens, Protozoan; Antigens, Surface; CD8-Positive T-Lymphocytes; Cattle; Protozoan Vaccines; Sporozoites; Theileria annulata; Theileria parva; Theileriasis; Vaccination; Vaccines, Attenuated
PubMed: 27647496
DOI: 10.1111/pim.12388