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Vaccination: Malaria Vaccine
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Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains Fungal and Parasitic Infections
The extended rod-like Plasmodium falciparum circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study indicated that the N-terminal domain might improve the efficacy of a new CSP vaccine. Using a panel of CSP-specific monoclonal antibodi...
Source: Infection and Immunity - September 10, 2015 Category: Infectious Diseases Authors: Herrera, R., Anderson, C., Kumar, K., Molina-Cruz, A., Nguyen, V., Burkhardt, M., Reiter, K., Shimp, R., Howard, R. F., Srinivasan, P., Nold, M. J., Ragheb, D., Shi, L., DeCotiis, M., Aebig, J., Lambert, L., Rausch, K. M., Muratova, O., Jin, A., Reed, S. Tags: Fungal and Parasitic Infections Source Type: research
Effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite Plasmodium yoelii
Transmission-blocking vaccine (TBV) is a promising strategy for interrupting the malaria transmission cycle. Current TBV candidates include both pre- and post-fertilization antigens expressed during sexual dev...
Source: Parasites and Vectors - August 8, 2016 Category: Microbiology Authors: Li Zheng, Wei Pang, Zanmei Qi, Enjie Luo, Liwang Cui and Yaming Cao Source Type: research
Evaluating antibody functional activity and strain-specificity of vaccine candidates for malaria in pregnancy using in vitro phagocytosis assays
Malaria in pregnancy is a major cause of poor maternal and infant health, and is associated with the sequestration of P. falciparum-infected erythrocytes (IE) in the placenta. The leading vaccine candidate for pr...
Source: Parasites and Vectors - January 29, 2018 Category: Microbiology Authors: Mirja Hommel, Jo-Anne Chan, Alexandra J. Umbers, Christine Langer, Stephen J. Rogerson, Joseph D. Smith and James G. Beeson Tags: Short report Source Type: research
Strong concordance between percent inhibition in oocyst and sporozoite intensities in a Plasmodium falciparum standard membrane-feeding assay
Effective malaria transmission-blocking vaccines (TBVs) can support malaria eradication programmes, and the standard membrane-feeding assay (SMFA) has been used as a “gold standard” assay for TBV development. ...
Source: Parasites and Vectors - May 6, 2019 Category: Microbiology Authors: Kazutoyo Miura, Bruce J. Swihart, Bingbing Deng, Luwen Zhou, Thao P. Pham, Ababacar Diouf, Michael P. Fay and Carole A. Long Tags: Research Source Type: research
Optimization of a multi‐stage, multi‐subunit malaria vaccine candidate for the production in Pichia pastoris by the identification and removal of protease cleavage sites
Abstract
We demonstrated the successful optimization of a recombinant multi‐subunit malaria vaccine candidate protein for production in the methylotrophic yeast Pichia pastoris by the identification and subsequent removal of two protease cleavage sites. After observing protein degradation in the culture supernatant of a fed‐batch fermentation, the predominant proteolytic fragment of the secreted recombinant protein was analyzed by mass spectrometry. The MS data indicated the cleavage of an amino acid sequence matching the yeast KEX2‐protease consensus motif EKRE. The cleavage in this region was completely abolished b...
Source: Biotechnology and Bioengineering - October 21, 2014 Category: Biomedical Science Authors: Holger Spiegel, Helga Schinkel, Robin Kastilan, Pia Dahm, Alexander Boes, Matthias Scheuermayer, Ivana Chudobová, Dominika Maskus, Rolf Fendel, Stefan Schillberg, Andreas Reimann, Rainer Fischer Tags: Biocatalysis, Protein Engineering and Nanobiotechnolgy Source Type: research
Immunization of Mice with Live-Attenuated Late Liver Stage-Arresting Plasmodium yoelii Parasites Generates Protective Antibody Responses to Preerythrocytic Stages of Malaria Microbial Immunity and Vaccines
Understanding protective immunity to malaria is essential for the design of an effective vaccine to prevent the large number of infections and deaths caused by this parasitic disease. To date, whole-parasite immunization with attenuated parasites is the most effective method to confer sterile protection against malaria infection in clinical trials. Mouse model studies have highlighted the essential role that CD8+ T cells play in protection against preerythrocytic stages of malaria; however, there is mounting evidence that antibodies are also important in these stages. Here, we show that experimental immunization of mice wi...
Source: Infection and Immunity - November 10, 2014 Category: Infectious Diseases Authors: Keitany, G. J., Sack, B., Smithers, H., Chen, L., Jang, I. K., Sebastian, L., Gupta, M., Sather, D. N., Vignali, M., Vaughan, A. M., Kappe, S. H. I., Wang, R. Tags: Microbial Immunity and Vaccines Source Type: research
A Replicating Adenovirus Capsid Display Recombinant Elicits Antibodies against Plasmodium falciparum Sporozoites in Aotus nancymaae Monkeys Microbial Immunity and Vaccines
Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) of Plasmodium falciparum on the virion surface. The recombinant induced P. falciparum sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the ...
Source: Infection and Immunity - December 16, 2014 Category: Infectious Diseases Authors: Karen, K. A., Deal, C., Adams, R. J., Nielsen, C., Ward, C., Espinosa, D. A., Xie, J., Zavala, F., Ketner, G. Tags: Microbial Immunity and Vaccines Source Type: research
Immune Characterization of Plasmodium falciparum Parasites with a Shared Genetic Signature in a Region of Decreasing Transmission Microbial Immunity and Vaccines
This study lays the groundwork for detailed investigations of the mechanisms driving the expansion or contraction of specific parasite clones in the population.
Source: Infection and Immunity - December 16, 2014 Category: Infectious Diseases Authors: Bei, A. K., Diouf, A., Miura, K., Larremore, D. B., Ribacke, U., Tullo, G., Moss, E. L., Neafsey, D. E., Daniels, R. F., Zeituni, A. E., Nosamiefan, I., Volkman, S. K., Ahouidi, A. D., Ndiaye, D., Dieye, T., Mboup, S., Buckee, C. O., Long, C. A., Wirth, D Tags: Microbial Immunity and Vaccines Source Type: research
Acquisition of Antibodies against Plasmodium falciparum Merozoites and Malaria Immunity in Young Children and the Influence of Age, Force of Infection, and Magnitude of Response Microbial Immunity and Vaccines
We examined antibodies (IgM, IgG, and IgG subclasses) to merozoite antigens and their relationship to the prospective risk of malaria in children 1 to 4 years of age in a region of malaria endemicity in Papua New Guinea. IgG, IgG1, and IgG3 responses generally increased with age, were higher in children with active infection, and reflected geographic heterogeneity in malaria transmission. Antigenic properties, rather than host factors, appeared to be the main determinant of the type of IgG subclass produced. High antibody levels were not associated with protection from malaria; in contrast, they were typically associated w...
Source: Infection and Immunity - January 14, 2015 Category: Infectious Diseases Authors: Stanisic, D. I., Fowkes, F. J. I., Koinari, M., Javati, S., Lin, E., Kiniboro, B., Richards, J. S., Robinson, L. J., Schofield, L., Kazura, J. W., King, C. L., Zimmerman, P., Felger, I., Siba, P. M., Mueller, I., Beeson, J. G. Tags: Microbial Immunity and Vaccines Source Type: research
Alga-Produced Malaria Transmission-Blocking Vaccine Candidate Pfs25 Formulated with a Human Use-Compatible Potent Adjuvant Induces High-Affinity Antibodies That Block Plasmodium falciparum Infection of Mosquitoes Microbial Immunity and Vaccines
A vaccine to prevent the transmission of malaria parasites from infected humans to mosquitoes is an important component for the elimination of malaria in the 21st century, yet it remains neglected as a priority of malaria vaccine development. The lead candidate for Plasmodium falciparum transmission-blocking vaccine development, Pfs25, is a sexual stage surface protein that has been produced for vaccine testing in a variety of heterologous expression systems. Any realistic malaria vaccine will need to optimize proper folding balanced against cost of production, yield, and potentially reactogenic contaminants. Here Chlamydo...
Source: Infection and Immunity - April 15, 2015 Category: Infectious Diseases Authors: Patra, K. P., Li, F., Carter, D., Gregory, J. A., Baga, S., Reed, S. G., Mayfield, S. P., Vinetz, J. M. Tags: Microbial Immunity and Vaccines Source Type: research
PD-1 Deficiency Enhances Humoral Immunity of Malaria Infection Treatment Vaccine Fungal and Parasitic Infections
Malaria infection treatment vaccine (ITV) is a promising strategy to induce homologous and heterologous protective immunity against the blood stage of the parasite. However, the underlying mechanism of protection remains largely unknown. Here, we found that a malaria-specific antibody (Ab) could mediate the protective immunity of ITV-immunized mice. Interestingly, PD-1 deficiency greatly elevated the levels of both malaria-specific total IgG and subclass IgG2a and enhanced the protective efficacy of ITV-immunized mice against the blood-stage challenge. A serum adoptive-transfer assay demonstrated that the increased Ab leve...
Source: Infection and Immunity - April 15, 2015 Category: Infectious Diseases Authors: Liu, T., Lu, X., Zhao, C., Fu, X., Zhao, T., Xu, W. Tags: Fungal and Parasitic Infections Source Type: research
Parity-Dependent Recognition of DBL1X-3X Suggests an Important Role of the VAR2CSA High-Affinity CSA-Binding Region in the Development of the Humoral Response against Placental Malaria Fungal and Parasitic Infections
Plasmodium falciparum multidomain protein VAR2CSA stands today as the leading vaccine candidate against pregnancy-associated malaria (PAM). Most of the studies aiming to decrypt how naturally acquired immunity develops have assessed the immune recognition of individual VAR2CSA Duffy-binding-like (DBL) domains, thus overlooking the presence of conformational epitopes resulting from the overall folding of the full-length protein. In order to characterize the development of humoral immunity toward VAR2CSA, we made use of a large cohort of 293 Senegalese pregnant women to assess the level of recognition by plasma IgG of the fu...
Source: Infection and Immunity - May 12, 2015 Category: Infectious Diseases Authors: Dechavanne, S., Srivastava, A., Gangnard, S., Nunes-Silva, S., Dechavanne, C., Fievet, N., Deloron, P., Chene, A., Gamain, B. Tags: Fungal and Parasitic Infections Source Type: research
Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax Fungal and Parasitic Infections
In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluore...
Source: Infection and Immunity - July 8, 2015 Category: Infectious Diseases Authors: Wang, B., Lu, F., Cheng, Y., Chen, J.-H., Jeon, H.-Y., Ha, K.-S., Cao, J., Nyunt, M. H., Han, J.-H., Lee, S.-K., Kyaw, M. P., Sattabongkot, J., Takashima, E., Tsuboi, T., Han, E.-T. Tags: Fungal and Parasitic Infections Source Type: research
Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera Microbial Immunity and Vaccines
Plasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimer...
Source: Infection and Immunity - August 12, 2015 Category: Infectious Diseases Authors: Cabrera-Mora, M., Fonseca, J. A., Singh, B., Oliveira-Ferreira, J., Lima-Junior, J. d. C., Calvo-Calle, J. M., Moreno, A. Tags: Microbial Immunity and Vaccines Source Type: research
Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection Microbial Immunity and Vaccines
Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stag...
Source: Infection and Immunity - September 10, 2015 Category: Infectious Diseases Authors: Leite, J. A., Bargieri, D. Y., Carvalho, B. O., Albrecht, L., Lopes, S. C. P., Kayano, A. C. A. V., Farias, A. S., Chia, W. N., Claser, C., Malleret, B., Russell, B., Castineiras, C., Santos, L. M. B., Brocchi, M., Wunderlich, G., Soares, I. S., Rodrigues Tags: Microbial Immunity and Vaccines Source Type: research
