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Protective efficacy of Eimeria maxima EmLPL and EmTregIM-1 against homologous challenge in chickens.Poultry Science Jul 2024Chicken coccidiosis has inflicted significant economic losses upon the poultry industry. The primary strategies for preventing and controlling chicken coccidiosis...
Chicken coccidiosis has inflicted significant economic losses upon the poultry industry. The primary strategies for preventing and controlling chicken coccidiosis include anticoccidial drugs and vaccination. However, these approaches face limitations, such as drug residues and resistance associated with anticoccidial drugs, and safety concerns related to live vaccines. Consequently, the urgent development of innovative vaccines, such as subunit vaccines, is imperative. In previous study, we screened 2 candidate antigens: Eimeria maxima lysophospholipase (EmLPL) and E. maxima regulatory T cell inducing molecule 1 (EmTregIM-1). To investigate the immune protective effect of the 2 candidate antigens against Eimeria maxima (E. maxima) infection, we constructed recombinant plasmids, namely pET-28a-EmLPL and pET-28a-EmTregIM-1, proceeded to induce the expression of recombinant proteins of EmLPL (rEmLPL) and EmTregIM-1 (rEmTregIM-1). The immunogenic properties of these proteins were confirmed through western blot analysis. Targeting EmLPL and EmTregIM-1, we developed subunit vaccines and encapsulated them in PLGA nanoparticles, resulting in nano-vaccines: PLGA-rEmLPL and PLGA-rEmTregIM-1. The efficacy of these vaccines was assessed through animal protection experiments. The results demonstrated that rEmLPL and rEmTregIM-1 were successfully recognized by anti-E. maxima chicken sera and His-conjugated mouse monoclonal antibodies. Immunization with both subunit and nano-vaccines containing EmLPL and EmTregIM-1 markedly mitigated weight loss and reduced oocyst shedding in chickens infected with E. maxima. Furthermore, the anticoccidial indexes (ACI) for both rEmLPL and PLGA-rEmLPL exceeded 160, whereas those for rEmTregIM-1 and PLGA-rEmTregIM-1 were above 120 but did not reach 160, indicating superior protective efficacy of the rEmLPL and PLGA-rEmLPL formulations. By contrast, the protection afforded by rEmTregIM-1 and PLGA-rEmTregIM-1 was comparatively lower. Thus, EmLPL is identified as a promising candidate antigen for vaccine development against E. maxima infection.
Topics: Animals; Eimeria; Coccidiosis; Chickens; Poultry Diseases; Protozoan Vaccines; Vaccines, Subunit; Antigens, Protozoan
PubMed: 38810564
DOI: 10.1016/j.psj.2024.103865 -
Nature Communications Mar 2024Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these...
Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these stages impact each other via perturbation of host responses, and this influences the outcome of natural infection. We sought to understand whether the parasite stage interplay would affect live-attenuated whole parasite vaccination, since the efficacy of whole parasite vaccines strongly correlates with their extend of development in the liver. We thus investigated the impact of BS infection on LS development of genetically attenuated and wildtype parasites in female rodent malaria models and observed that for both, LS infection suffered severe suppression during concurrent BS infection. Strikingly and in contrast to previously published studies, we find that the BS-induced iron-regulating hormone hepcidin is not mediating suppression of LS development. Instead, we demonstrate that BS-induced host interferons are the main mediators of LS developmental suppression. The type of interferon involved depended on the BS-causing parasite species. Our study provides important mechanistic insights into the BS-mediated suppression of LS development. This has direct implications for understanding the outcomes of live-attenuated Plasmodium parasite vaccination in malaria-endemic areas and might impact the epidemiology of natural malaria infection.
Topics: Female; Humans; Malaria Vaccines; Hepcidins; Malaria; Plasmodium; Liver; Liver Diseases
PubMed: 38453916
DOI: 10.1038/s41467-024-46270-3 -
The Lancet. Infectious Diseases Jan 2024Seasonal vaccination with the RTS,S/AS01 vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either... (Randomized Controlled Trial)
Randomized Controlled Trial
Seasonal vaccination with RTS,S/AS01 vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.
BACKGROUND
Seasonal vaccination with the RTS,S/AS01 vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years.
METHODS
This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01 plus placebo SMC, or SMC plus RTS,S/AS01. They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01-alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete.
FINDINGS
In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01-alone group, and 133 in the combined group. The combination of RTS,S/AS01 and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01 (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01 was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01-alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected.
INTERPRETATION
Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission.
FUNDING
UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation).
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Infant; Child, Preschool; Mali; Burkina Faso; Seasons; Malaria; Malaria Vaccines; Vaccination; Chemoprevention; Malaria, Falciparum
PubMed: 37625434
DOI: 10.1016/S1473-3099(23)00368-7 -
Veterinary Parasitology Dec 2023The global poultry industry has experienced dramatic growth in recent decades, increasing the significance of pathogens of chickens. Protozoan parasites of the genus...
The global poultry industry has experienced dramatic growth in recent decades, increasing the significance of pathogens of chickens. Protozoan parasites of the genus Eimeria can cause the disease coccidiosis, compromising animal health and welfare, and incurring significant annual costs. Seven Eimeria species have long been recognised to infect chickens, supplemented by three new candidate species first reported from Australia in 2007/8. Named Eimeria lata, Eimeria nagambie and Eimeria zaria, one or more of these new species have been reported in Australia, several countries in sub-Saharan Africa, India, Venezuela, and most recently the United States of America, but none have been detected in Europe. Here, a panel of 56 unvaccinated broiler chicken farms were sampled in the final week of production from France, Greece, Italy, the Netherlands, the Republic of Ireland, and the United Kingdom to assess the occurrence of all ten Eimeria species using specific polymerase chain reaction (PCR). Overall, 39 of 56 (69.6%) farms were found to host at least one species. Eimeria acervulina, E. tenella, and E. maxima were most common, with E. mitis and E. praecox also widespread. Eimeria necatrix was detected on one farm in France, while E. brunetti was not detected. Eimeria zaria was detected for the first time in Europe, appearing in Greece and Italy (one occurrence each). New primers were designed to confirm detection of E. zaria and provide template for phylogenetic comparison with the reference isolate from Australia. Detection of E. zaria in Europe reinforces the importance of integrated control for coccidiosis given the lack of protection induced by current anticoccidial vaccines.
Topics: Animals; Eimeria; Chickens; Phylogeny; Poultry Diseases; Nigeria; Coccidiosis
PubMed: 37931476
DOI: 10.1016/j.vetpar.2023.110068 -
The Journal of Clinical Investigation Apr 2024BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).
Topics: Adult; Humans; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins; Adjuvants, Immunologic; Antigens, Protozoan; Aluminum Hydroxide; Antibodies, Protozoan; Malaria; Malaria, Falciparum
PubMed: 38290009
DOI: 10.1172/JCI175707 -
Microbial Biotechnology Mar 2024Chicken coccidiosis is an intestinal disease caused by the parasite Eimeria, which severely damages the growth of chickens and causes significant economic losses in the...
Chicken coccidiosis is an intestinal disease caused by the parasite Eimeria, which severely damages the growth of chickens and causes significant economic losses in the poultry industry. Improvement of the immune protective effect of antigens to develop high efficiency subunit vaccines is one of the hotspots in coccidiosis research. Sporozoite-specific surface antigen 1 (SAG1) of Eimeria tenella (E. tenella) is a well-known protective antigen and is one of the main target antigens for the development of subunit, DNA and vector vaccines. However, the production and immunoprotective effects of SAG1 need to be further improved. Here, we report that both SAG1 from E. tenella and its fusion protein with the xylanase XynCDBFV-SAG1 are recombinant expressed and produced in Pichia pastoris (P. pastoris). The substantial expression quantity of fusion protein XynCDBFV-SAG1 is achieved through fermentation in a 15-L bioreactor, reaching up to about 2 g/L. Moreover, chickens immunized with the fusion protein induced higher protective immunity as evidenced by a significant reduction in the shedding of oocysts after E. tenella challenge infection compared with immunized with recombinant SAG1. Our results indicate that the xylanase enhances the immunogenicity of subunit antigens and has the potential for developing novel molecular adjuvants. The high expression level of fusion protein XynCDBFV-SAG1 in P. pastoris holds promise for the development of effective recombinant anti-coccidial subunit vaccine.
Topics: Animals; Eimeria tenella; Chickens; Antigens, Surface; Antigens, Protozoan; Coccidiosis; Recombinant Proteins; Vaccines, Synthetic; Saccharomycetales
PubMed: 38478376
DOI: 10.1111/1751-7915.14447 -
Veterinary Parasitology Oct 2023Eimeria, protozoan parasites that can cause the disease coccidiosis, pose a persistent challenge to poultry production and welfare. Control is commonly achieved using...
Eimeria, protozoan parasites that can cause the disease coccidiosis, pose a persistent challenge to poultry production and welfare. Control is commonly achieved using good husbandry supplemented with routine chemoprophylaxis and/or live parasite vaccination, although widespread drug resistance and challenges to vaccine supply or cost can prove limiting. Extensive effort has been applied to develop subunit anticoccidial vaccines as scalable, cost-effective alternatives, but translation to the field will require a robust understanding of parasite diversity. Using a new Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) panel we begin to describe the genetic diversity of Eimeria acervulina populations in Africa and Europe. PCR-RFLP genotyping E. acervulina populations sampled from commercial broiler and layer chickens reared in Nigeria or the United Kingdom (UK) and Republic of Ireland (RoI) revealed comparable levels of haplotype diversity, in direct contrast to previous descriptions from the close relative E. tenella. Here, 25 distinct PCR-RFLP haplotypes were detected from a panel of 42 E. acervulina samples, including 0.7 and 0.5 haplotypes per sample in Nigeria (n = 20) and the UK/RoI (n = 14), respectively. All but six haplotypes were found to be country-specific. The PCR-RFLP markers immune mapped protein 1 (IMP1) and heat shock protein 90 (HSP90) were most informative for Nigerian E. acervulina, while microneme protein 3 (MIC3) and HSP90 were most informative in UK/RoI populations. High haplotype diversity within E. acervulina populations may indicate frequent genetic exchange and potential for rapid dissemination of genetic material associated with escape from selective barriers such as anticoccidial drugs and future subunit vaccines.
PubMed: 37634263
DOI: 10.1016/j.vetpar.2023.110010 -
Animals : An Open Access Journal From... Jul 2023is a protozoan parasite that causes histomonosis in gallinaceous birds such as turkeys and chickens. Since the banning and restricted usage of effective drugs such as...
is a protozoan parasite that causes histomonosis in gallinaceous birds such as turkeys and chickens. Since the banning and restricted usage of effective drugs such as nitarsone, 80-100% morbidity and mortality occur in turkeys and 20-30% mortality in chickens. New ideas are needed to resolve the re-emergence of histomonosis in poultry. In this study, the α-actinin encoding gene from was cloned. The 1839-bp gene encoding 612 amnio acids showed close phylogenetic relationships with and . It was then inserted into the prokaryotic expression vector pET28a(+) and induced with isopropyl-β-D-thiogalactopyranoside. A 73 kDa recombinant protein rHmα-actinin 1 was obtained and purified with a Ni-NTA chromatography column. rHmα-actinin 1 was recognized by mouse anti-rHmα-actinin 1 polyclonal antibody, mouse anti-rHmα-actinin 1 monoclonal antibody, and rehabilitation sera from infected chickens. Native α-actinin 1 in the total proteins of can also be detected with mouse anti-rHmα-actinin monoclonal antibody. Immunolocalization assays showed that Hmα-actinin 1 was mainly distributed in the cytoplasm of virulent histomonads JSYZ-D9 and in the peripheral regions (near the plasma membrane) of attenuated histomonads JSYZ-D195. Based on experiment, when chickens were subcutaneously immunized with rHmα-actinin 1 at 5 and 12 days old and then challenged with at 19 days old, rHmα-actinin 1 reduced the lesion scores 12 days after infection (31 days old) and increased the body weight gain during the challenged period (19-31 days old). Furthermore, it also strengthened the cellular and humoral immune responses 7 days after the second immunization (19 days old). In conclusion, Hmα-actinin 1 could be used as a candidate antigen to develop vaccines against chicken histomonosis.
PubMed: 37508107
DOI: 10.3390/ani13142330 -
EMBO Molecular Medicine Apr 2024Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection...
Vaccination with infectious Plasmodium falciparum (Pf) sporozoites (SPZ) administered with antimalarial drugs (PfSPZ-CVac), confers superior sterilizing protection against infection when compared to vaccination with replication-deficient, radiation-attenuated PfSPZ. However, the requirement for drug administration constitutes a major limitation for PfSPZ-CVac. To obviate this limitation, we generated late liver stage-arresting replication competent (LARC) parasites by deletion of the Mei2 and LINUP genes (mei2/linup or LARC2). We show that Plasmodium yoelii (Py) LARC2 sporozoites did not cause breakthrough blood stage infections and engendered durable sterilizing immunity against various infectious sporozoite challenges in diverse strains of mice. We next genetically engineered a PfLARC2 parasite strain that was devoid of extraneous DNA and produced cryopreserved PfSPZ-LARC2. PfSPZ-LARC2 liver stages replicated robustly in liver-humanized mice but displayed severe defects in late liver stage differentiation and did not form liver stage merozoites. This resulted in complete abrogation of parasite transition to viable blood stage infection. Therefore, PfSPZ-LARC2 is the next-generation vaccine strain expected to unite the safety profile of radiation-attenuated PfSPZ with the superior protective efficacy of PfSPZ-CVac.
Topics: Animals; Mice; Plasmodium falciparum; Malaria, Falciparum; Parasites; Gene Deletion; Malaria Vaccines; Vaccines, Attenuated; Sporozoites
PubMed: 38514791
DOI: 10.1038/s44321-024-00057-7 -
Malaria Journal Aug 2023A workshop on implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission, was held...
A workshop on implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission, was held as a hybrid meeting in Dakar, Senegal, and online, 23-25 January 2023. Delegates from Expanded Programmes on Immunization (EPI) and National Malaria Control Programmes (NMCPs) from 13 African countries, and representatives from key stakeholders participated. RTS,S is the first malaria vaccine to be recommended by the World Health Organization (WHO). The recommendation followed pilot implementation of the vaccine in Ghana, Kenya and Malawi, which showed that introduction of the vaccine was highly effective at scale, and was associated with a 30% reduction in hospital admissions with severe malaria in age groups eligible to have received the vaccine and no evidence of the safety signals that had been observed in the phase 3 trial. Clinical trials in Mali and Burkina Faso, showed that in children receiving Seasonal Malaria Chemoprevention (SMC), providing the vaccine just prior to high transmission seasons, matching the period of highest efficacy to the peak transmission season, resulted in substantial reduction in the incidence of clinical malaria and of severe malaria. While SMC has been successfully scaled-up despite the challenges of delivery, there is no established platform for seasonal vaccine delivery and no real-world experience. The objectives of this workshop were, therefore, to share experiences from countries that have introduced the RTS,S vaccine in routine child vaccination programmes, with SMC-implementing countries as they consider malaria vaccine introduction, and to explore implementation strategies in countries with seasonal transmission and where EPI coverage may be low especially in the second year of life. Practical implementation challenges, lessons learned for vaccine introduction, and research questions, towards facilitating the introduction of the RTS,S (and other malaria vaccines) in countries with seasonal malaria transmission were discussed.
Topics: Child; Humans; Burkina Faso; Malaria Vaccines; Seasons; Senegal; Vaccination
PubMed: 37612716
DOI: 10.1186/s12936-023-04657-5