Plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified IgG antibodies from malaria-resistant mice

Kamali, Alí N.; Marín-García, Patricia; Azcárate, Isabel G.; Díez, Amalia; Puyet, Antonio; Bautista, José M.

doi:10.1016/j.imbio.2012.05.002

Cited by 10 publications

(13 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, in both treated mouse groups, the repertoire of Py17XL antigens recognized by the specific IgGs raised was also amplified after each re‐infection, as observed for acquired malaria immunity in humans, which is likely to depend on the accumulation of a wide repertoire of antigenic specificities over a long time (Kinyanjui et al ., ) and which parallels with a gradual gaining of clinical immunity (see Bull et al ., ). After both treatments, mice showed IgG binding to merozoite antigens and internal antigens of Py17XL infected RBCs, as identified recently in a similar experimental set (Kamali et al ., ). Because internal antigens are only exposed in disrupted target cells, they are detected as secreted antigens, which seem to induce antibody responses more efficiently than membrane and cytoplasmic antigens due to an enhanced ability to reach the lymph node (Boyle et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Insights into the preclinical treatment of blood‐stage malaria by the antibiotic borrelidin

Azcárate

Marín-García

Camacho

et al. 2013

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEBlood-stage Plasmodium parasites cause morbidity and mortality from malaria. Parasite resistance to drugs makes development of new chemotherapies an urgency. Aminoacyl-tRNA synthetases have been validated as antimalarial drug targets. We explored long-term effects of borrelidin and mupirocin in lethal P. yoelii murine malaria. EXPERIMENTAL APPROACHLong-term (up to 340 days) immunological responses to borrelidin or mupirocin were measured after an initial 4 day suppressive test. Prophylaxis and cure were evaluated and the inhibitory effect on the parasites analysed. KEY RESULTSBorrelidin protected against lethal malaria at 0.25 mg·kg. Antimalarial activity of borrelidin correlated with accumulation of trophozoites in peripheral blood. All infected mice treated with borrelidin survived and subsequently developed immunity protecting them from re-infection on further challenges, 75 and 340 days after the initial infection. This long-term immunity in borrelidin-treated mice resulted in negligible parasitaemia after re-infections and marked increases in total serum levels of antiparasite IgGs with augmented avidity. Long-term memory IgGs mainly reacted against high and low molecular weight parasite antigens. Immunofluorescence microscopy showed that circulating IgGs bound predominantly to late intracellular stage parasites, mainly schizonts. CONCLUSIONS AND IMPLICATIONSLow borrelidin doses protected mice from lethal malaria infections and induced protective immune responses after treatment. Development of combination therapies with borrelidin and selective modifications of the borrelidin molecule to specifically inhibit plasmodial threonyl tRNA synthetase should improve therapeutic strategies for malaria. AbbreviationsARS, aminoacyl-tRNA synthetases; IleRS, isoleucyl t-RNA synthetase; NAI, naturally acquired immunity; pi, post-infection; Py17XL, P. yoelii 17XL; ThrRS, threonyl t-RNA synthetase

show abstract

Section: Discussionmentioning

confidence: 97%

Insights into the preclinical treatment of blood‐stage malaria by the antibiotic borrelidin

Azcárate

Marín-García

Camacho

et al. 2013

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Interestingly, immunization with the translation elongation factor EF-2 identified by 2-DE and MALDI in Brugia malayi adult worm protected the host from challenge infection with thirdstage larvae [36]. Furthermore, a study using malariaprotective IgG identified a member of the heat-shock protein family, the eukaryotic translation initiation factor 3, and a ribosome-associated protein, which were considered vaccine candidates [37]. The only transcription factor identified in the present study was elongin C, which is essential for viral pathogenesis and replication, but there is no evidence that this protein may play a key role in protozoan pathogenesis [38].…”

Section: Discussionmentioning

confidence: 99%

Immunoproteomic and mass spectrometric analysis of Eimeria acervulina antigens recognized by antisera from chickens infected with E. acervulina, E. tenella or E. necatrix

Liu

Tuo

et al. 2020

Parasites Vectors

View full text Add to dashboard Cite

Background: Coccidiosis is caused by Eimeria spp. and can result in severe economic losses to the global poultry industry. Due to anticoccidial drug resistance rapidly developing in the parasites and drug residues in poultry products, efficacious and safe alternative coccidia control measures are needed. The objective of the present study was to identify common protective antigens which may be used as vaccine candidates in the development of subunit, multivalent, cross-protective vaccines against most of the economically important Eimeria species.Methods: Whole sporozoite proteins of Eimeria acervulina were prepared and analyzed by 2-dimensional gel electrophoresis (2-DE) followed by western blotting using immune sera specific to E. tenella, E. acervulina, or E. necatrix. The protein spots detected by all three immune sera were then excised from the preparative gel and protein ID was performed by MALDI-TOF-MS/MS. Results:Approximately 620 E. acervulina sporozoite protein spots were demonstrated by 2-DE with silver staining, among which 23 protein spots were recognized by immune sera specific to all three Eimeria species. The results showed that 21 putative E. acervulina proteins were identified, which include proteins with known enzymatic properties, and those which are involved in protein translation, transport and trafficking, and ribosomal biogenesis and functions. There is one protein which may be involved in transcription and one heat-shock protein. Two proteins contain predicted domains, but with no apparent functions known. There were 2 protein spots which had no detectable proteins. None of the proteins has a predicted signal peptide or a transmembrane domain; however, 6 of the 21 putative proteins were predicted to be potentially secretory through the non-classical pathway. Conclusions:Our study identified a diverse group of antigens immunologically common to all three Eimeria species, none of which was previously characterized and tested as a vaccine candidate. Further research on immunogenicity and cross-protective potential of these individual proteins as vaccine candidates will aid the development of vaccines against the most common and pathogenic Eimeria spp.

show abstract

“…Remarkably, circulating Abs against high MW PyL Ags were preferably maintained after several months without parasite re-exposure. In a recent proteomic study, we identified some of these PyL Ags with Abs from protected S mice, as a new strategy to develop multi-Ag-based vaccine therapies [85]. The goal of the serum-transfer experiments was to determine the protective capacity of the humoral response at the time reaching its maximum in a given group of infected mice.…”

Section: Discussionmentioning

confidence: 99%

Differential Immune Response Associated to Malaria Outcome Is Detectable in Peripheral Blood following Plasmodium yoelii Infection in Mice

et al. 2014

Self Cite

View full text Add to dashboard Cite

Malaria infection in humans elicits a wide range of immune responses that can be detected in peripheral blood, but we lack detailed long-term follow-up data on the primary and subsequent infections that lead to naturally acquired immunity. Studies on antimalarial immune responses in mice have been based on models yielding homogenous infection profiles. Here, we present a mouse model in which a heterogeneous course of Plasmodium yoelii lethal malaria infection is produced in a non-congenic ICR strain to allow comparison among different immunological and clinical outcomes. Three different disease courses were observed ranging from a fatal outcome, either early or late, to a self-resolved infection that conferred long-term immunity against re-infection. Qualitative and quantitative changes produced in leukocyte subpopulations and cytokine profiles detected in peripheral blood during the first week of infection revealed that monocytes, dendritic cells and immature B cells were the main cell subsets present in highly-parasitized mice dying in the first week after infection. Besides, CD4+CD25high T cells expanded at an earlier time point in early deceased mice than in surviving mice and expressed higher levels of intracellular Foxp3 protein. In contrast, survivors showed a limited increase of cytokines release and stable circulating innate cells. From the second week of infection, mice that would die or survive showed similar immune profiles, although CD4+CD25high T cells number increased earlier in mice with the worst prognosis. In surviving mice the expansion of activated circulating T cell and switched-class B cells with a long-term protective humoral response from the second infection week is remarkable. Our results demonstrate that the follow-up studies of immunological blood parameters during a malaria infection can offer information about the course of the pathological process and the immune response.

show abstract

Plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified IgG antibodies from malaria-resistant mice

Cited by 10 publications

References 60 publications

Insights into the preclinical treatment of blood‐stage malaria by the antibiotic borrelidin

Insights into the preclinical treatment of blood‐stage malaria by the antibiotic borrelidin

Immunoproteomic and mass spectrometric analysis of Eimeria acervulina antigens recognized by antisera from chickens infected with E. acervulina, E. tenella or E. necatrix

Differential Immune Response Associated to Malaria Outcome Is Detectable in Peripheral Blood following Plasmodium yoelii Infection in Mice

Contact Info

Product

Resources

About