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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 -
Human Vaccines Nov 2011Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of... (Review)
Review
Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of 20-40% of the patients infected with Trypanosoma cruzi, the protozoan parasite responsible for the disease. A vaccine would be key to improve disease control and we review here the recent advances and challenges of a T. cruzi vaccine. There is a growing consensus that a protective immune response requires the activation of a Th1 immune profile, with the stimulation of CD8 (+) T cells. Several vacines types, including recombinant proteins, DNA and viral vectors, as well as heterologous prime-boost combinations, have been found immunogenic and protective in mouse models, providing proof-of-concept data on the feasibility of a preventive or therapeutic vaccine to control a T. cruzi infection. However, several challenges such as better end-points, safety issues and trial design need to be addressed for further vaccine development to proceed.
Topics: Animals; Chagas Disease; Disease Models, Animal; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Protozoan Proteins; Protozoan Vaccines; Trypanosoma cruzi; Vaccination
PubMed: 22048121
DOI: 10.4161/hv.7.11.17016 -
Parasitology Apr 2014Effective vaccines are available for many protozoal diseases of animals, including vaccines for zoonotic pathogens and for several species of vector-transmitted... (Review)
Review
Effective vaccines are available for many protozoal diseases of animals, including vaccines for zoonotic pathogens and for several species of vector-transmitted apicomplexan haemoparasites. In comparison with human diseases, vaccine development for animals has practical advantages such as the ability to perform experiments in the natural host, the option to manufacture some vaccines in vivo, and lower safety requirements. Although it is proper for human vaccines to be held to higher standards, the enduring lack of vaccines for human protozoal diseases is difficult to reconcile with the comparatively immense amount of research funding. Common tactical problems of human protozoal vaccine research include reliance upon adapted rather than natural animal disease models, and an overwhelming emphasis on novel approaches that are usually attempted in replacement of rather than for improvement upon the types of designs used in effective veterinary vaccines. Currently, all effective protozoal vaccines for animals are predicated upon the ability to grow protozoal organisms. Because human protozoal vaccines need to be as effective as animal vaccines, researchers should benefit from a comparison of existing veterinary products and leading experimental vaccine designs. With this in mind, protozoal vaccines are here reviewed.
Topics: Animals; Disease Models, Animal; Humans; Malaria; Protozoan Infections; Protozoan Vaccines; Research Support as Topic; Vaccination; Veterinary Medicine
PubMed: 24476952
DOI: 10.1017/S0031182013002060 -
Animal : An International Journal of... Jun 2013Vaccination against rumen methanogens offers a practical approach to reduce methane emissions in livestock, particularly ruminants grazing on pasture. Although... (Review)
Review
Vaccination against rumen methanogens offers a practical approach to reduce methane emissions in livestock, particularly ruminants grazing on pasture. Although successful vaccination strategies have been reported for reducing the activity of the rumen-dwelling organism Streptococcus bovis in sheep and S. bovis and Lactobacillus spp. in cattle, earlier approaches using vaccines based on whole methanogen cells to reduce methane production in sheep have produced less promising results. An anti-methanogen vaccine will need to have broad specificity against methanogens commonly found in the rumen and induce antibody in saliva resulting in delivery of sufficiently high levels of antibodies to the rumen to reduce methanogen activity. Our approach has focussed on identifying surface and membrane-associated proteins that are conserved across a range of rumen methanogens. The identification of potential vaccine antigens has been assisted by recent advances in the knowledge of rumen methanogen genomes. Methanogen surface proteins have been shown to be immunogenic in ruminants and vaccination of sheep with these proteins induced specific antibody responses in saliva and rumen contents. Current studies are directed towards identifying key candidate antigens and investigating the level and types of salivary antibodies produced in sheep and cattle vaccinated with methanogen proteins, stability of antibodies in the rumen and their impact on rumen microbial populations. In addition, there is a need to identify adjuvants that stimulate high levels of salivary antibody and are suitable for formulating with protein antigens to produce a low-cost and effective vaccine.
Topics: Animals; Bacteria; Bacterial Vaccines; Cattle; Eukaryota; Euryarchaeota; Methane; Protozoan Vaccines; Rumen; Sheep
PubMed: 23739467
DOI: 10.1017/S1751731113000682 -
Acta Tropica Dec 2019Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute... (Review)
Review
Trypanosoma cruzi (T. cruzi) is the causative agent for Chagas disease (CD). There is a critical lack of methods for prevention of infection or treatment of acute infection and chronic disease. Studies in experimental models have suggested that the protective immunity against T. cruzi infection requires the elicitation of Th1 cytokines, lytic antibodies and the concerted activities of macrophages, T helper cells, and cytotoxic T lymphocytes (CTLs). In this review, we summarize the research efforts in vaccine development to date and the challenges faced in achieving an efficient prophylactic or therapeutic vaccine against human CD.
Topics: Animals; Chagas Disease; Humans; Protozoan Vaccines; Trypanosoma cruzi
PubMed: 31513763
DOI: 10.1016/j.actatropica.2019.105168 -
Human Vaccines & Immunotherapeutics Feb 2013Toxoplasmosis is caused by the protozoan parasite T. gondii. Humans and other warm-blooded animals are its hosts. The infection has a worldwide distribution; one-third... (Review)
Review
Toxoplasmosis is caused by the protozoan parasite T. gondii. Humans and other warm-blooded animals are its hosts. The infection has a worldwide distribution; one-third of the world's population has been exposed to this parasite. There are three primary ways of transmission: ingesting uncooked meat containing tissue cysts, ingesting food and water contaminated with oocysts from infected cat feces and congenitally. Those particularly at risk of developing clinical illness include pregnant women, given that the parasite can pose a serious threat to the unborn child if the mother becomes infected while pregnant, and immunosuppressed individuals such as tissue transplant subjects, AIDS subjects, those with certain types of cancer and those undergoing certain forms of cancer therapy. Maternal infections early in pregnancy are less likely to be transmitted to the fetus than infections later in pregnancy, but early fetal infections are more likely to be severe than later infections. In the absence of an effective human vaccine, prevention of zoonotic transmission might be the best way to approach the problem of toxoplasmosis and must be done by limiting exposure to oocysts or tissue cysts. Vaccine development to prevent feline oocyst shedding is ongoing, mostly with live vaccines. The S48 strain Toxovax is a live vaccine originally developed for use in sheep, but when used in cats inhibits sexual development of T. gondii. This vaccine is used in sheep to reduce tissue cyst development. The T-263 strain of T. gondii is a live mutant strain designed to reduce or prevent oocyst shedding by cats by developing only partial infection in the feline intestinal tract.
Topics: Animals; Cats; Disease Transmission, Infectious; Drug Discovery; Humans; Protozoan Vaccines; Sheep; Toxoplasma; Toxoplasmosis, Animal; Vaccination; Zoonoses
PubMed: 23111123
DOI: 10.4161/hv.22474 -
Human Vaccines & Immunotherapeutics 2014Entamoeba histolytica is the causative agent of amebiasis, one of the top three parasitic causes of mortality worldwide. In the majority of infected individuals, E.... (Review)
Review
Entamoeba histolytica is the causative agent of amebiasis, one of the top three parasitic causes of mortality worldwide. In the majority of infected individuals, E. histolytica asymptomatically colonizes the large intestine, while in others, the parasite breaches the mucosal epithelial barrier to cause amebic colitis and can disseminate to soft organs to cause abscesses. Vaccinations using native and recombinant forms of the parasite Gal-lectin have been successful in protecting animals against intestinal amebiasis and amebic liver abscess. Protection against amebic liver abscesses has also been reported by targeting other E. histolytica components including the serine-rich protein and the 29-kDa-reductase antigen. To date, vaccines against the Gal-lectin hold the most promise but clinical trials will be required to validate its efficacy in humans. Here, we review the current strategies and future perspectives involved in the development of a vaccine against E. histolytica.
Topics: Animals; Disease Models, Animal; Drug Discovery; Entamoeba histolytica; Entamoebiasis; Humans; Protozoan Vaccines
PubMed: 24504133
DOI: 10.4161/hv.27796 -
Molekuliarnaia Biologiia 2015Many innovative researches on the development and introduction of recombinant vaccines against many economically important parasites were carried out in the 20th... (Review)
Review
Many innovative researches on the development and introduction of recombinant vaccines against many economically important parasites were carried out in the 20th century. Research continues to hold promise with the development of immunological and molecular approaches for control of these parasites and in this regard it has already been seen that blood-sucking parasites such as Haemonchus contortus and Ostertagia ostertagi are susceptible to control by vaccines containing "novel" or "concealed" antigens. Haemonchus contortus is primarily pathogenic to sheep and its blood-feeding behaviour causes effects ranging from mild anaemia to mortality in young animals. Current means of control which are dependent on repeated treatment with anthelmintics are responsible for the increasing drug resistance of this parasite. Together with the growing concern of residual chemicals in the environment and food chain, this has led to attempts to better understand the biology of the parasite with an aim to develop alternate means of control, including the development of molecular vaccines. More problematic and also important is the formulation and delivery strategy to induce expulsion of this parasite, using vaccines containing recombinant "conventional" antigens. Tremendous progress has been made in the last decade in identifying several antigens from Haemonchus contortus which in their native form stimulate useful levels of protective immunity. Vaccines have been developed against H. contortus using 'novel' gut antigens from the parasite, but variable responsiveness of the host sheep has resulted in varying degrees of protection which are stimulated by these vaccines. Computer models have also been used to simulate vaccine efficacy in worm control and have yielded good results. This review will try to summarise the protective efficacy and also the molecular properties of principal candidate antigens which are expressed by this parasite. The review will try to cover the aspirations, current success, limitations and problems faced by researchers in the control of this economically important parasite.
Topics: Animals; Antigens, Helminth; Haemonchiasis; Haemonchus; Protozoan Vaccines; Sheep
PubMed: 26710767
DOI: 10.7868/S002689841506021X -
Journal of Postgraduate Medicine 2003Leishmaniasis, a parasitic disease transmitted by the bite of some species of sandflies affects various age groups depending on the infecting Leishmania species,... (Review)
Review
Leishmaniasis, a parasitic disease transmitted by the bite of some species of sandflies affects various age groups depending on the infecting Leishmania species, geographic location, disease reservoir, and host immunocompetence. Visceral leishmaniasis is the most severe form of the disease affecting children. The extent and presentation of the disease depend on several factors, including the humoral and cell-mediated immune response of the host, the virulence of the infecting species, and the parasite burden. Children are at greater risk than adults in endemic areas. Malnutrition contributes to the development of disease, and incomplete therapy of initial disease is a risk factor for recurrence of leishmaniasis. Children usually present with intermittent fever, paleness, refusal to feed or anorexia, weight loss, and abdominal distension. Splenomegaly, hepatomegaly, lymph node enlargement, thrombocytopaenia, anaemia, leukopaenia and hypergammaglobulinemia are the most common findings in Paediatric leishmaniasis. Molecular methods appear to offer the promise of accurate non-invasive tools for the diagnosis of Leishmaniasis. Till these methods are evaluated, definite diagnosis will rely on the demonstration of the infecting parasite in various tissues. World-wide, with the notable exception of India, pentavalent antimonial compounds remain the most effective and the most affordable therapy for this disease. Lipid formulations of amphotericin B were assessed as short duration treatment and were proved to be effective. However, their cost precludes their wide use in developing countries. Miltefosine, a new oral agent, might prove effective, safe, and affordable. Strategies aimed at control of the micro-population of sandflies, eradication of canine leishmaniasis, and offering personal protection against sandfly bites, together with health education programs in developing countries, can help control the disease. Development of an effective vaccine remains a priority.
Topics: Animals; Antiprotozoal Agents; Child; Developing Countries; Humans; Leishmania donovani; Leishmaniasis, Visceral; Protozoan Vaccines; Risk Factors
PubMed: 12865569
DOI: 10.4103/0022-3859.930 -
The Indian Journal of Medical Research Mar 2006A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and... (Review)
Review
A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.
Topics: Animals; Drug Design; Drug Industry; Humans; International Cooperation; Leishmaniasis; Protozoan Vaccines; Public Health; Vaccines, DNA
PubMed: 16778321
DOI: No ID Found