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Biochimica Et Biophysica Acta. General... Nov 2021Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years... (Review)
Review
Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years worldwide. Different approaches are being used for treatment of this infection and its consequences, but limited results have been achieved and new therapeutics are still needed. One of the most interesting biotherapeutics in this era are Nanobodies which have shown very promising results in recent researches. Scope of review Here, we have reviewed the potentials of Nanobodies in Covid-19 treatment. We have also discussed the properties of these biotherapeutics that make them very suitable for pulmonary drug delivery, which seems to be very important route of administration in this disease. Major conclusion Nanobodies with their special biological and biophysical characteristics and their resistance against harsh manufacturing condition, can be considered as promising, targeted biotherapeutics which can be administered by pulmonary delivery pharmaceutical systems against Covid-19. General significance Covid-19 has become a global problem during the last two years and with emerging mutant strains, prophylactic and therapeutic approaches are still highly needed. Nanobodies with their specific properties can be considered as valuable and promising candidates in Covid-19 therapy.
Topics: Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing; Antiviral Agents; COVID-19; Camelus; Drug Delivery Systems; Humans; Immune Sera; Immunologic Factors; Lung; Molecular Targeted Therapy; Peptide Library; Protein Binding; SARS-CoV-2; Single-Domain Antibodies; Spike Glycoprotein, Coronavirus
PubMed: 34343644
DOI: 10.1016/j.bbagen.2021.129974 -
Critical Care (London, England) Mar 2020
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Disease Outbreaks; Humans; Immune Sera; Immunization, Passive; Pandemics; Plasma; Pneumonia, Viral; SARS-CoV-2; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 32178711
DOI: 10.1186/s13054-020-2818-6 -
Viruses Mar 2022Pseudorabies, caused by the pseudorabies virus (PRV), is an acute fatal disease, which can infect rodents, mammals, and other livestock and wild animals across species....
Pseudorabies, caused by the pseudorabies virus (PRV), is an acute fatal disease, which can infect rodents, mammals, and other livestock and wild animals across species. Recently, the emergence of PRV virulent isolates indicates a high risk of a variant PRV epidemic and the need for continuous surveillance. In this study, PRV-GD and PRV-JM, two fatal PRV variants, were isolated and their pathogenicity as well as their effects on host natural immune responses were assessed. PRV-GD and PRV-JM were genetically closest to PRV variants currently circulating in Heilongjiang (HLJ8) and Jiangxi (JX/CH/2016), which belong to genotype 2.2. Consistently, antisera from sows immunized with PRV-Ea classical vaccination showed much lower neutralization ability to PRV-GD and PRV-JM. However, the antisera from the pigs infected with PRV-JM had an extremely higher neutralization ability to PRV-TJ (as a positive control), PRV-GD and PRV-JM. In vivo, PRV-GD and PRV-JM infections caused 100% death in mice and piglets and induced extensive tissue damage, cell death, and inflammatory cytokine release. Our analysis of the emergence of PRV variants indicate that pigs immunized with the classical PRV vaccine are incapable of providing sufficient protection against these PRV isolates, and there is a risk of continuous evolution and virulence enhancement. Efforts are still needed to conduct epidemiological monitoring for the PRV and to develop novel vaccines against this emerging and reemerging infectious disease.
Topics: Animals; Antibodies, Viral; Female; Herpesvirus 1, Suid; Immune Sera; Immunity; Mammals; Mice; Pseudorabies Vaccines; Swine; Swine Diseases; Vaccines; Virulence
PubMed: 35458442
DOI: 10.3390/v14040712 -
Transplantation Oct 2020
Topics: Antilymphocyte Serum; Immunosuppression Therapy; Intestines; Rituximab
PubMed: 31978039
DOI: 10.1097/TP.0000000000003081 -
PLoS Neglected Tropical Diseases Oct 2020Snakebite is a neglected tropical disease that leads to more than 120,000 deaths every year. In 2019, World Health Organization (WHO) launched a strategy to decrease its... (Review)
Review
INTRODUCTION
Snakebite is a neglected tropical disease that leads to more than 120,000 deaths every year. In 2019, World Health Organization (WHO) launched a strategy to decrease its global burden by 2030. There is a range of issues around different interventions for the management of snakebite. Decisions around these interventions should be informed by evidence from systematic reviews (SR).
METHODS
An overview of SRs was conducted by searching 12 electronic databases, PROSPERO, contacting experts and screening the bibliography of included reviews. Screening, data extraction, and quality assessment (through AMSTAR-2) was done by at least two overview authors independently with discrepancies sorted by consensus. A narrative synthesis was conducted.
PRINCIPLE FINDINGS
The overview found 13 completed SRs that has looked at various aspects of management of snakebite envenomation. There was one SR on first aid, nine on effectiveness and safety of snake anti-venom (SAV), two on drugs to prevent adverse reactions due to SAV therapy, and one on surgical interventions for management of snakebite envenomation. All, except one, SR was appraised to have critically low confidence as per AMSTAR-2 Criteria. Evidence base was restricted to few studies for most interventions.
DISCUSSION
High quality evidence from SRs is required to inform guidelines and health system decisions which can bring down the burden of snakebite. The review indicates the need to fund high-quality SRs, evidence gaps and core outcome sets which can inform guideline recommendations, funding priorities for conduct of future trials. Variation in species distribution as well as intra-species variation in venom composition implies the need for conduct of region or, nation or state (sub-national) specific randomised controlled trials and SRs on different SAVs and their dosing regimens.
Topics: Animals; Antivenins; Disease Management; First Aid; Humans; Snake Bites; Snakes; Systematic Reviews as Topic
PubMed: 33048936
DOI: 10.1371/journal.pntd.0008727 -
Frontiers in Immunology 2021This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the... (Review)
Review
This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund's adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed 'low dose, low volume multi-site' was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand's annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a 'diverse toxin repertoire' composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the 'diverse toxin repertoire', the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.
Topics: Adjuvants, Immunologic; Animals; Antibody Specificity; Antivenins; Elapid Venoms; Elapidae; Epitopes; Horses; Humans; Immunization; Neurotoxins; Snake Bites
PubMed: 33968072
DOI: 10.3389/fimmu.2021.668328 -
Biochemical and Biophysical Research... Jan 20213-methylglutaconic (3MGC) aciduria is associated with a growing number of discrete inborn errors of metabolism. Herein, an antibody-based approach to...
3-methylglutaconic (3MGC) aciduria is associated with a growing number of discrete inborn errors of metabolism. Herein, an antibody-based approach to detection/quantitation of 3MGC acid has been pursued. When trans-3MGC acid conjugated keyhole limpet hemocyanin (KLH) was inoculated into rabbits a strong immune response was elicited. Western blot analysis provided evidence that immune serum, but not pre-immune serum, recognized 3MGC-conjugated bovine serum albumin (BSA). In competition ELISAs using isolated immune IgG, the limit of detection for free trans-3MGC acid was compared to that for cis-3MGC acid and four structurally related short-chain dicarboxylic acids. Surprisingly, cis-3MGC acid yielded a much lower limit of detection (∼0.1 mg/ml) than trans-3MGC acid (∼1.0 mg/ml) while all other dicarboxylic acids tested were poor competitors. The data suggest trans-3MGC- isomerized during, or after, conjugation to KLH such that the immunogen was actually comprised of KLH harboring a mixture of cis- and trans-3MGC haptens. To investigate this unexpected isomerization reaction, trans-3MGC CoA was prepared and incubated at 37 °C in the presence of BSA. Evidence was obtained that non-enzymatic isomerization of trans-3MGC CoA to cis-3MGC CoA precedes intramolecular catalysis to form cis-3MGC anhydride plus CoASH. Anhydride-dependent acylation of BSA generated 3MGCylated BSA, as detected by anti-3MGC immunoblot. The results presented provide an explanation for the unanticipated detection of 3MGCylated proteins in a murine model of primary 3MGC aciduria. Furthermore, non-enzymatic hydrolysis of cis-3MGC anhydride represents a potential source of cis-3MGC acid found in urine of subjects with 3MGC aciduria.
Topics: Acylation; Animals; Coenzyme A; Dicarboxylic Acids; Glutarates; Haptens; Hemocyanins; Hot Temperature; Immune Sera; Immunoglobulin G; Isomerism; Rabbits; Serum Albumin, Bovine
PubMed: 33280817
DOI: 10.1016/j.bbrc.2020.11.100 -
Nature Communications Apr 2023While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity...
While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.
Topics: Animals; Humans; COVID-19 Vaccines; Ferritins; COVID-19; SARS-CoV-2; Geranium; Immune Sera; Nanoparticles; Primates; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37069151
DOI: 10.1038/s41467-023-37417-9 -
Archives of Disease in Childhood.... Feb 2020There are inconsistencies in how newborns are managed following exposure to varicella, ranging from reassurance and observation to administration of varicella zoster... (Review)
Review
There are inconsistencies in how newborns are managed following exposure to varicella, ranging from reassurance and observation to administration of varicella zoster immunoglobulin (VZIG) and admission to hospital for varying length courses of intravenous aciclovir.Hospitalised preterm babies exposed to varicella should receive VZIG. Administration can otherwise be limited to pregnant non-immune women or to newborns if there is development of maternal chickenpox from 5 days prior to delivery up to 48 hours postdelivery. Intravenous aciclovir is only recommended in cases of newborn disease despite VZIG or in severe disease. The use of VZIG may not prevent varicella but may reduce severity of disease.In this article, we review the evidence for risk to non-immune mothers, the fetus and newborns who had different types of exposure to varicella, with recommendations for management and treatment of confirmed neonatal chickenpox.
Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Female; Humans; Immune Sera; Infant, Newborn; Infant, Premature; Pregnancy; Pregnancy Complications, Infectious
PubMed: 31122930
DOI: 10.1136/archdischild-2018-316715 -
The Journal of Clinical Investigation Oct 2020Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher...
Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. Allergen transcripts translate into proteins with a cationic carboxy terminus depleted in hydrophobic residues. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions.
Topics: 2S Albumins, Plant; Adolescent; Allergens; Anaphylaxis; Animals; Antigens, Plant; Arachis; Cattle; Child; Child, Preschool; Fabaceae; Female; Frameshifting, Ribosomal; Genetic Variation; Humans; Immune Sera; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Milk Hypersensitivity; Peanut Hypersensitivity; Phaseolus; Plant Proteins; Recombinant Proteins; Glycine max; Transcription, Genetic
PubMed: 32634131
DOI: 10.1172/JCI126275