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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 -
BioMed Research International 2019Malaria is a disease of public health importance in many parts of the world. Currently, there is no effective way to eradicate malaria, so developing safe, efficient,... (Review)
Review
Malaria is a disease of public health importance in many parts of the world. Currently, there is no effective way to eradicate malaria, so developing safe, efficient, and cost-effective vaccines against this disease remains an important goal. Current research on malaria vaccines is focused on developing vaccines against pre-erythrocytic stage parasites and blood-stage parasites or on developing a transmission-blocking vaccine. Here, we briefly describe the progress made towards a vaccine against , the most pathogenic of the malaria parasite species to infect humans.
Topics: Animals; Antigens, Protozoan; Cost-Benefit Analysis; Erythrocytes; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 31687404
DOI: 10.1155/2019/9751471 -
Immunity, Inflammation and Disease Jun 2023In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically... (Review)
Review
INTRODUCTION
In malaria-stricken regions, malaria continues to be one of the primary causes of mortality for children. The number of malaria-related fatalities has drastically decreased because of artemisinin-based pharmacological regimens.
METHODS
Two independent researchers did a comprehensive literature search using PubMed/MEDLINE and Google Scholar from its inception to September 2022.
RESULTS
After evaluating RTS, S/AS01 for its safety, effectiveness, and feasibility, the European Medicines Agency (EMA) issued a favorable conclusion. It was suggested that the RTS, S malaria vaccine be used extensively by the World Health Organization on October 6, 2021. The successful pilot program testing the malaria vaccine in Ghana, Kenya, and Malawi served as the basis for this proposal.
CONCLUSION
Several challenges need to be addressed to ensure the success of vaccination programs. From the acceptability perspective, issues such as inadequate community engagement, concerns about side effects, and issues with the delivery and quality of healthcare services can affect the acceptance of the vaccine. From the feasibility standpoint, factors such as lack of transportation or long distances to healthcare facilities and the perception of completion of the vaccination calendar can affect the feasibility of the vaccine. Lastly, the availability of the vaccine is also a major concern as it may not be readily available to meet the demands.
Topics: Child; Humans; Malaria Vaccines; Feasibility Studies; Drug-Related Side Effects and Adverse Reactions; Ghana; Kenya
PubMed: 37382251
DOI: 10.1002/iid3.899 -
Cell Reports. Medicine Nov 2023Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation...
Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting in vivo adaptive responses have a different T1/T2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.
Topics: Animals; Mice; Liposomes; Th1 Cells; Emulsions; Adjuvants, Immunologic; Malaria Vaccines; Malaria
PubMed: 37913775
DOI: 10.1016/j.xcrm.2023.101245 -
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 -
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 -
Malaria Journal Jun 2022Malaria control relies heavily on the use of anti-malarial drugs and insecticides against malaria parasites and mosquito vectors. Drug and insecticide resistance... (Review)
Review
Malaria control relies heavily on the use of anti-malarial drugs and insecticides against malaria parasites and mosquito vectors. Drug and insecticide resistance threatens the effectiveness of conventional malarial interventions; alternative control approaches are, therefore, needed. The development of malaria transmission-blocking vaccines that target the sexual stages in humans or mosquito vectors is among new approaches being pursued. Here, the immunological mechanisms underlying malaria transmission blocking, status of Pfs25-based vaccines are viewed, as well as approaches and capacity for first in-human evaluation of a transmission-blocking candidate vaccine Pfs25-IMX313/Matrix-M administered to semi-immune healthy individuals in endemic settings. It is concluded that institutions in low and middle income settings should be supported to conduct first-in human vaccine trials in order to stimulate innovative research and reduce the overdependence on developed countries for research and local interventions against many diseases of public health importance.
Topics: Animals; Humans; Insecticide Resistance; Malaria Vaccines; Mosquito Vectors; Nanoparticles; Saponins
PubMed: 35655174
DOI: 10.1186/s12936-022-04173-y -
Trends in Parasitology Jul 2019Malaria kills more than 600 000 people yearly, mainly children, and eradication is a global priority. Malaria transmission-blocking vaccines are advancing in clinical... (Review)
Review
Malaria kills more than 600 000 people yearly, mainly children, and eradication is a global priority. Malaria transmission-blocking vaccines are advancing in clinical trials, and strategies for their introduction must be prioritized among stakeholders and the vulnerable populations exposed to the disease.
Topics: Clinical Trials as Topic; Humans; Malaria; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins; Vulnerable Populations
PubMed: 31153722
DOI: 10.1016/j.pt.2019.04.008