-
Frontiers in Immunology 2021Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of... (Review)
Review
Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.
Topics: Animals; Coinfection; Drug Design; Drug Development; Endemic Diseases; Host-Parasite Interactions; Humans; Immunogenicity, Vaccine; Praziquantel; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 33746974
DOI: 10.3389/fimmu.2021.635985 -
Parasites & Vectors Jul 2015Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. It has extensive host populations and is prevalent globally; T. gondii infection can cause... (Review)
Review
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. It has extensive host populations and is prevalent globally; T. gondii infection can cause a zoonotic parasitic disease. Microneme protein 3 (MIC3) is a secreted protein that is expressed in all stages of the T. gondii life cycle. It has strong immunoreactivity and plays an important role in the recognition, adhesion and invasion of host cells by T. gondii. This article reviews the molecular structure of MIC3, its role in the invasion of host cells by parasites, its relationship with parasite virulence, and its induction of immune protection to lay a solid foundation for an in-depth study of potential diagnostic agents and vaccines for preventing toxoplasmosis.
Topics: Amino Acid Sequence; Animals; Cell Adhesion; Humans; Life Cycle Stages; Molecular Sequence Data; Protozoan Proteins; Protozoan Vaccines; Sequence Alignment; Toxoplasma; Toxoplasmosis, Animal; Vaccines, DNA; Virulence
PubMed: 26194005
DOI: 10.1186/s13071-015-1001-4 -
International Journal For Parasitology Feb 2019The increase in human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe... (Review)
Review
The increase in human babesiosis is of major concern to health authorities. In the USA, most of these cases are due to infections with Babesia microti, whereas in Europe B. divergens is the major cause of clinical disease in humans. Here we review the immunological and biological literature of glycosylphosphatidylinositol (GPI)-anchored merozoite proteins of human Babesia parasites with emphasis on their role in immunity, and provide some new bioinformatical information on B. microti GPI-Anchored Proteins (GPI-AP). Cattle can be vaccinated with soluble parasite antigens (SPA) of Babesia divergens that are released by the parasite during proliferation. The major component in SPA preparations appeared to be a 37 kDa merozoite surface protein that is anchored in the merozoite membrane by a GPI anchor. Animals could be protected by vaccination with the recombinant 37 kDa protein expressed in Escherichia coli, provided the protein had a hydrophobic terminal sequence. Based on this knowledge, a recombinant vaccine was developed against Babesia canis infection in dogs, successfully. In order to identify similar GPI-AP in B. microti, the genome was analysed. Here it is shown that B. microti encodes all proteins necessary for GPI assembly and its subsequent protein transfer. In addition, in total 21 genes encoding for GPI-AP were detected, some of which reacted particularly strongly with sera from B. microti-infected human patients. Reactivity of antibodies with GPI-anchored merozoite proteins appears to be dependent on the structural conformation of the molecule. It is suggested that the three-dimensional structure of the protein that is anchored in the membrane is different from that of the protein that has been shed from the merozoite surface. The significance of this protein's dynamics in parasite biology and immune evasion is discussed. Finally, we discuss developments in tick and Babesia vaccine research, and the role such vaccines could play in the control of human babesiosis.
Topics: Animals; Antigens, Protozoan; Babesia microti; Babesiosis; Disease Models, Animal; Dogs; Protozoan Vaccines; Vaccines, Synthetic
PubMed: 30684517
DOI: 10.1016/j.ijpara.2018.12.002 -
Acta Tropica May 2020Poultry industry has been very instrumental in curtailing malnutrition and poverty and as such contributing to economic growth. However, production loss in poultry... (Review)
Review
Poultry industry has been very instrumental in curtailing malnutrition and poverty and as such contributing to economic growth. However, production loss in poultry industry due to parasitic disease such as coccidiosis has become a global challenge. Chicken coccidiosis is an enteric disease that is associated with morbidity and mortality. The control of this parasite through anticoccidial live vaccines and drugs has been very successful though with some limitations such as the cost of production of live vaccines, and drugs resistance which is a public health concern. The discovery of Eimeria vaccine antigens such as Apical membrane antigens (AMA)-1 and Immune mapped protein (IMP)-1 have introduced the use of recombinant vaccines as alternative control measures against chicken coccidiosis. Although some protections have been reported among recombinant vaccines, improving their protective efficacy has triggered the search for a novel and efficient delivery vehicle. Transgenic Eimeria, which is constructed either through stable or transient transfection is currently being explored as novel delivery vehicle of Eimeria vaccine antigens. Due to partial protections reported in chickens vaccinated with transgenic Eimeria lines expressing different Eimeria antigens, improving protective efficacy becomes imperative. Recent trends in the design of transgenic Eimeria for potential application in the control of chicken coccidiosis are summarized in this review. We conclude that, with improved protective efficacy using multiple vaccine antigens, transgenic Eimeria parasite could fill the gap in the control of chicken coccidiosis as an efficient anticoccidial vaccine.
Topics: Animals; Chickens; Coccidiosis; Eimeria; Organisms, Genetically Modified; Poultry Diseases; Protozoan Vaccines
PubMed: 32105666
DOI: 10.1016/j.actatropica.2020.105417 -
The Journal of Infectious Diseases Jan 2015
Topics: Animals; Chagas Disease; Computational Biology; Protozoan Vaccines; Trypanosoma cruzi
PubMed: 25070940
DOI: 10.1093/infdis/jiu420 -
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 -
Trends in Parasitology Feb 2016Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness.... (Review)
Review
Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness. Humans establish such interactions with a consortium of microorganisms known as the microbiota. Despite the mutualistic nature of these interactions, some bacterial components of the human microbiota express immunogenic glycans that elicit glycan-specific antibody (Ab) responses. The ensuing circulating Abs are protective against infections by pathogens that express those glycans, as demonstrated for Plasmodium, the causative agent of malaria. Presumably, a similar protective Ab response acts against other vector-borne diseases.
Topics: Antibodies; Biological Evolution; Host-Pathogen Interactions; Humans; Intestines; Malaria, Falciparum; Microbiota; Plasmodium falciparum; Polysaccharides; Protozoan Vaccines
PubMed: 26774793
DOI: 10.1016/j.pt.2015.11.004 -
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 -
Infection, Genetics and Evolution :... Nov 2017Eimeria species parasites can cause the disease coccidiosis, most notably in chickens. The occurrence of coccidiosis is currently controlled through a combination of... (Review)
Review
Eimeria species parasites can cause the disease coccidiosis, most notably in chickens. The occurrence of coccidiosis is currently controlled through a combination of good husbandry, chemoprophylaxis and/or live parasite vaccination; however, scalable, cost-effective subunit or recombinant vaccines are required. Many antigens have been proposed for use in novel anticoccidial vaccines, supported by the capacity to reduce disease severity or parasite replication, increase body weight gain in the face of challenge or improve feed conversion under experimental conditions, but none has reached commercial development. Nonetheless, the protection against challenge induced by some antigens has been within the lower range described for the ionophores against susceptible isolates or current live vaccines prior to oocyst recycling. With such levels of efficacy it may be that combinations of anticoccidial antigens already described are sufficient for development as novel multi-valent vaccines, pending identification of optimal delivery systems. Selection of the best antigens to be included in such vaccines can be informed by knowledge defining the natural occurrence of specific antigenic diversity, with relevance to the risk of immediate vaccine breakthrough, and the rate at which parasite genomes can evolve new diversity. For Eimeria, such data are now becoming available for antigens such as apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) and more are anticipated as high-capacity, high-throughput sequencing technologies become increasingly accessible.
Topics: Animals; Antigenic Variation; Chickens; Coccidia; Coccidiosis; Coccidiostats; Protozoan Vaccines; Vaccines, Synthetic
PubMed: 29017798
DOI: 10.1016/j.meegid.2017.10.009 -
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