scholarly journals In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors

2022 ◽  
Vol 3 ◽  
Author(s):  
Gabriel Rojas-Jiménez ◽  
Daniela Solano ◽  
Álvaro Segura ◽  
Andrés Sánchez ◽  
Stephanie Chaves-Araya ◽  
...  
Keyword(s):  
Low Income ◽  
Neutralizing Antibodies ◽  
Caprylic Acid ◽  
Passive Immunization ◽  
Intravenous Immunoglobulins ◽  
Pilot Scale ◽  
Low Income Countries ◽  
Efficacy And Safety ◽  
Therapeutic Alternative

Despite vaccines are the main strategy to control the ongoing global COVID-19 pandemic, their effectiveness could not be enough for individuals with immunosuppression. In these cases, as well as in patients with moderate/severe COVID-19, passive immunization with anti-SARS-CoV-2 immunoglobulins could be a therapeutic alternative. We used caprylic acid precipitation to prepare a pilot-scale batch of anti-SARS-CoV-2 intravenous immunoglobulins (IVIg) from plasma of donors immunized with the BNT162b2 (Pfizer-BioNTech) anti-COVID-19 vaccine (VP-IVIg) and compared their in vitro efficacy and safety with those of a similar formulation produced from plasma of COVID-19 convalescent donors (CP-IVIg). Both formulations showed immunological, physicochemical, biochemical, and microbiological characteristics that meet the specifications of IVIg formulations. Moreover, the concentration of anti-RBD and ACE2-RBD neutralizing antibodies was higher in VP-IVIg than in CP-IVIg. In concordance, plaque reduction neutralization tests showed inhibitory concentrations of 0.03–0.09 g/L in VP-IVIg and of 0.06–0.13 in CP-IVIg. Thus, VP-IVIg has in vitro efficacy and safety profiles that justify their evaluation as therapeutic alternative for clinical cases of COVID-19. Precipitation with caprylic acid could be a simple, feasible, and affordable alternative to produce formulations of anti-SARS-CoV-2 IVIg to be used therapeutically or prophylactically to confront the COVID-19 pandemic in middle and low-income countries.

scholarly journals Position of Scientific Oncological Societies Towards Biosimilar Antibodies

Breast Care ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Bernhard Wörmann ◽  
Marianne Sinn
Keyword(s):  
Monoclonal Antibodies ◽  
Low Income ◽  
Financial Burden ◽  
Informed Consent Process ◽  
Low Income Countries ◽  
Efficacy And Safety ◽  
Economic Competition ◽  
Off Label ◽  
Careful Documentation

First biosimilars of monoclonal antibodies have recently been approved in oncology. Biosimilars enable economic competition, alleviate the financial burden for insurances, and may facilitate access to these drugs in low-income countries. Biosimilars are not completely identical to the original drug. The approval of biosimilars is only partially based on results of randomized clinical studies. In the introduction phase of new biosimilars, this can lead to uncertainties for patients and physicians. Based on the current clinical data and experiences, biosimilars of monoclonal antibodies in oncology show no significant differences in pharmacokinetics, efficacy, and safety in comparison to the patented originals. Scientific medical societies recommend the use of biosimilar monoclonal antibodies and support switching in long-term treatments. However, the use of biosimilars for off-label indications requires additional attention towards efficacy and safety. Active counselling of the patient by the treating physician is the most important step in the informed consent process, especially when switching from an original to a biosimilar. Careful documentation of the prescribed drug and enhanced pharmacovigilance are recommended for the use of biosimilars.

scholarly journals Nematicidal Activity of Stevia rebaudiana (Bertoni) Assisted by Phytochemical Analysis

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 319
Author(s):  
Nikoletta Ntalli ◽  
Konstantinos M. Kasiotis ◽  
Eirini Baira ◽  
Christos L. Stamatis ◽  
Kyriaki Machera
Keyword(s):  
Low Income ◽  
Stevia Rebaudiana ◽  
Nematicidal Activity ◽  
Low Income Countries ◽  
In Vitro Tests ◽  
Phytochemical Analysis ◽  
Inoculum Level ◽  
Water Extracts

To date, there has been great demand for ecofriendly nematicides with beneficial properties to the nematode hosting plants. Great efforts are made towards the chemical characterization of botanical extracts exhibiting nematicidal activity against Meloidogyne spp., but only a small percentage of these data are actually used by the chemical industry in order to develop new formulates. On the other hand, the ready to use farmer produced water extracts based on edible plants could be a sustainable and economic solution for low income countries. Herein, we evaluate the nematicidal potential of Stevia rebaudiana grown in Greece against Meloidogyne incognita and Meloidogyne javanica, two most notorious phytoparasitic nematode species causing great losses in tomato cultivation worldwide. In an effort to recycle the plant’s remnants, after leaves selection for commercial use, we use both leaves and wooden stems to test for activity. In vitro tests demonstrate significant paralysis activity of both plant parts’ water extracts against the second-stage juvenile (J2) of the parasites; while, in vivo bioassays demonstrated the substantial efficacy of leaves’ powder (95% at 1 g kg−1) followed by stems. Interestingly, the incorporation of up to 50 g powder/kg of soil is not phytotoxic, which demonstrates the ability to elevate the applied concentration of the nematicidal stevia powder under high inoculum level. Last but not least, the chemical composition analyses using cutting edge analytical methodologies, demonstrated amongst components molecules of already proven nematicidal activity, was exemplified by several flavonoids and essential oil components. Interestingly, and to our knowledge, for the flavonoids, morin and robinin, the anthocyanidin, keracyanin, and a napthalen-2-ol derivative is their first report in Stevia species.

scholarly journals Influenza prevention and treatment by passive immunization.

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Barbara Kalenik ◽  
Róża Sawicka ◽  
Anna Góra-Sochacka ◽  
Agnieszka Sirko
Keyword(s):  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Egg Yolk ◽  
Passive Immunity ◽  
Protective Effects ◽  
In Vivo Experiments ◽  
Effective Care ◽  
Antibody Preparations

Passive immunity is defined as a particular antigen resistance provided by external antibodies. It can be either naturally or artificially acquired. Natural passive immunization occurs during pregnancy and breast-feeding in mammals and during hatching in birds. Maternal antibodies are passed through the placenta and milk in mammals and through the egg yolk in birds. Artificial passive immunity is acquired by injection of either serum from immunized (or infected) individuals or antibody preparations. Many independent research groups worked on selection, verification and detailed characterization of polyclonal and monoclonal antibodies against the influenza virus. Numerous antibody preparations were tested in a variety of in vitro and in vivo experiments for their efficacy to neutralize the virus. Here, we describe types of antibodies tested in such experiments and their viral targets, review approaches resulting in identification of broadly neutralizing antibodies and discuss methods used to demonstrate their protective effects. Finally, we shortly discuss the phenomenon of maternal antibody transfer as a way of effective care for young individuals and as an interfering factor in early vaccination.

scholarly journals Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917

2021 ◽  
Author(s):  
Ilia Gelfat ◽  
Yousuf Aqeel ◽  
Jacquiline M Tremblay ◽  
Justyna Jaskiewicz ◽  
Anishma Shrestha ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Low Income ◽  
Shiga Toxin ◽  
Microbial Pathogens ◽  
Low Income Countries ◽  
Bacterial Toxin ◽  
Scanning Electron Micrographs ◽  
E Coli ◽  
Curli Fiber

Enteric microbial pathogens, including Escherichia coli, Shigella and Cryptosporidium species, take a particularly heavy toll in low-income countries and are highly associated with infant mortality. We describe here a means to display anti-infective agents on the surface of a probiotic bacterium. Because of their stability and versatility, VHHs, the variable domains of camelid heavy-chain-only antibodies, have potential as components of novel agents to treat or prevent enteric infectious disease. We isolated and characterized VHHs targeting several enteropathogenic Escherichia.coli (EPEC) virulence factors: flagellin (Fla), which is required for bacterial motility and promotes colonization; both intimin and the translocated intimin receptor (Tir), which together play key roles in attachment to enterocytes; and E. coli secreted protein A (EspA), an essential component of the type III secretion system (T3SS) that is required for virulence. Several VHHs that recognize Fla, intimin, or Tir blocked function in vitro. The probiotic strain E. coli Nissle 1917 (EcN) produces on the bacterial surface curli fibers, which are the major proteinaceous component of E. coli biofilms. A subset of Fla-, intimin-, or Tir-binding VHHs, as well as VHHs that recognize either a T3SS of another important bacterial pathogen (Shigella flexneri), a soluble bacterial toxin (Shiga toxin or Clostridioides difficile toxin TcdA), or a major surface antigen of an important eucaryotic pathogen (Cryptosporidium parvum) were fused to CsgA, the major curli fiber subunit. Scanning electron micrographs indicated CsgA-VHH fusions were assembled into curli fibers on the EcN surface, and Congo Red binding indicated that these recombinant curli fibers were produced at high levels. Ectopic production of these VHHs conferred on EcN the cognate binding activity and, in the case of anti-Shiga toxin, was neutralizing. Taken together, these results demonstrate the potential of the curli-based pathogen sequestration strategy described herein and contribute to the development of novel VHH-based gut therapeutics.

scholarly journals Mice immunized with the vaccine candidate HexaPro spike produce neutralizing antibodies against SARS-CoV-2

2021 ◽  
Author(s):  
Chotiwat Seephetdee ◽  
Nattawut Buasri ◽  
Kanit Bhukhai ◽  
Kitima Srisanga ◽  
Suwimon Manopwisedjaroen ◽  
...  
Keyword(s):  
Low Income ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Physical Property ◽  
Cost Effective ◽  
Low Income Countries ◽  
Subunit Vaccines ◽  
Neutralization Activity ◽  
Boost Regimen ◽  
Global Logistics

Updated and revised versions of COVID-19 vaccines are vital due to genetic variations of the SARS-CoV-2 spike antigen. Furthermore, vaccines that are safe, cost-effective, and logistically friendly are critically needed for global equity, especially for middle to low income countries. Recombinant protein-based subunit vaccines against SARS-CoV-2 have been reported with the use of the receptor binding domain (RBD) and the prefusion spike trimers (S-2P). Recently, a new version of prefusion spike trimers, so called "HexaPro", has been shown for its physical property to possess two RBD in the "up" conformation, as opposed to just one exposed RBD found in S-2P. Importantly, this HexaPro spike antigen is more stable than S-2P, raising its feasibility for global logistics and supply chain. Here, we report that the spike protein HexaPro offers a promising candidate for SARS-CoV-2 vaccine. Mice immunized by the recombinant HexaPro adjuvanted with aluminium hydroxide using a prime-boost regimen produced high-titer neutralizing antibodies for up to 56 days after initial immunization against live SARS-CoV-2 infection. In addition, the level of neutralization activity is comparable to that of convalescence sera. Our results indicate that the HexaPro subunit vaccine confers neutralization activity in sera collected from mice receiving the prime-boost regimen.

scholarly journals The development of a nano-sized eggshell and titanium dioxide desensitising paste to re-mineralise teeth

2019 ◽  
Author(s):  
◽  
Stanley Chibuzor Onwubu
Keyword(s):  
Calcium Carbonate ◽  
Low Income ◽  
Logistic Equation ◽  
Low Income Countries ◽  
Hydrated Silica ◽  
Dentin Tubule ◽  
The Cost ◽  
Bovine Enamel ◽  
New Evidence

in). Manuscript I established that as the brushing days increase the remineralisation or dentin tubule occluded by each respective desensitising agent improved. It was found that the occluding capabilities of EB@TiO2 were more superior to both Pro-argin and NovaMin products in both saliva and without saliva. Manuscript II described the use of the logistic equation to predict the remineralisation of the EB@TiO2. Manuscript II established that the logistic equation effectively predicted the remineralisation trends of EB@TiO2 and Pro-argin toothpaste (Colgate Pro-relief). Manuscript III assesses the abrasivity of EB@TiO2 in comparison with calcium carbonate, and hydrated silica containing toothpaste. Bovine enamel specimen was used for the in vitro experiment. Manuscript III established that enamel loss from the brushed surface, regardless of the sample group, were statistically different when compared to the covered surface. The study found that the abrasivity of EB@TiO2 were comparable with the calcium carbonate toothpaste. It was also established that EB@TiO2 was less abrasive when compared against hydrated silica containing toothpaste. In conclusion, the experimental finding has exhaustively provided evidence on the suitability of EB@TiO2 as an active ingredient in toothpaste formulation. The study, therefore, provides new evidence and approach for the management of DH, particularly in low-income countries where the cost of oral healthcare may be too high.

Repertoire and Neutralizing Activity of Antibodies Against Hepatitis C Virus E2 Peptide in Patients With Spontaneous Resolution of Hepatitis C

2019 ◽  
Vol 220 (7) ◽  
pp. 1209-1218 ◽  
Author(s):  
Anne Olbrich ◽  
Hedda Wardemann ◽  
Stephan Böhm ◽  
Karen Rother ◽  
Che C Colpitts ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Neutralizing Antibodies ◽  
Recombinant Expression ◽  
Passive Immunization ◽  
Immunoglobulin Gene ◽  
Neutralizing Activity ◽  
Polymerase Chain ◽  
Immunoglobulin Repertoire

AbstractNeutralizing antibodies can prevent hepatitis C virus (HCV) infection, one of the leading causes of cirrhosis and liver cancer. Here, we characterized the immunoglobulin repertoire of memory B-cell antibodies against a linear epitope in the central front layer of the HCV envelope (E2; amino acids 483–499) in patients who were infected in a single-source outbreak. A reverse transcription polymerase chain reaction–based immunoglobulin gene cloning and recombinant expression approach was used to express monoclonal antibodies from HCV E2 peptide–binding immunoglobulin G–positive memory B cells. We identified highly mutated antibodies with a neutralizing effect in vitro against different genotype isolates sharing similar gene features. Our data confirm the importance of VH1–69 use for neutralizing activity. The data offer a promising basis for vaccine research and the use of anti-E2 antibodies as a means of passive immunization.

scholarly journals Prevalence of Treponema species in the Gut Microbiome is Linked to Bifidobacterium sp. and Bacteroides sp.

2020 ◽  
Author(s):  
Souad BELKACEMI ◽  
MARYAM TIDJANI ALOU ◽  
Matthieu MILLION ◽  
Anthony LEVASSEUR ◽  
Saber KHELAIFIA ◽  
...  
Keyword(s):  
Low Income ◽  
Bifidobacterium Longum ◽  
Nutrition Transition ◽  
Human Microbiome ◽  
Bifidobacterium Bifidum ◽  
Low Income Countries ◽  
And Function ◽  
Gastro Intestinal Tract ◽  
Fermented Dairy

Abstract BackgroundTreponema species as commensals of the human microbiome have a prevalence and function depending on the studied niche. In the oral cavity, treponemes are ubiquitous while they have been strictly linked to rural and ancestral populations in the gastro-intestinal tract and are undetected in urban populations. In this study, an in silico analysis of 1481 metagenomes, selected based on the previous detection of treponemes in such sample types, was conducted to predict putative bacterial antagonists of treponemes, i.e. bacteria present when treponemes are lacking and vice versa. Predicted antagonists were subsequently tested in-vitro against Treponema denticola CSUR P7640.ResultsMost frequent predicted antagonists included members of the Bifidobacteriaceae family (23.3%) among which Bifidobacterium longum was the most significant (63.3% in T- group, p <0.0000001) as well as members of the Bacteroides (6.7%) and Streptococcus (13.3%) genera. The relative abundance of the aforementioned taxa was also anticorrelated with that of the Treponema genus in the metagenomes analyzed in this study. B. longum CSUR P7400, Bifidobacterium bifidum CSUR P1194, Bifidobacterium breve CSUR P7882, Bacteroides ovatus CSUR P4577, Bacteroides uniformis CSUR P2248 and Bacteroides thetaiotaomicron CSUR P7324 were able to inhibit the growth of T. denticola with B. longum being the most efficient.ConclusionsThese results highlight an antagonism between Bifidobacterium species, known probiotics and bio-preservatives, and Treponema spp. This may help to explain the variation of Treponema prevalence in high-income countries and middle- and low-income countries which might linked to the differential consumption of fermented dairy foodstuff and processed food and therefore to the phenomenon of nutrition transition.

scholarly journals New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention and Cure

2021 ◽  
Author(s):  
Hui Li ◽  
Shuyi Wang ◽  
Fang-Hua Lee ◽  
Ryan S. Roark ◽  
Alex I. Murphy ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Rhesus Macaques ◽  
Passive Immunization ◽  
Design Strategy ◽  
Efficient Replication ◽  
Hiv 1

Previously, we showed that substitution of HIV-1 Env residue 375-Ser by bulky aromatic residues enhances binding to rhesus CD4 and enables primary HIV-1 Envs to support efficient replication as simian-human immunodeficiency virus (SHIV) chimeras in rhesus macaques (RMs). Here, we test this design strategy more broadly by constructing SHIVs containing ten primary Envs corresponding to HIV-1 subtypes A, B, C, AE and AG. All ten SHIVs bearing wildtype Env375 residues replicated efficiently in human CD4+ T cells, but only one replicated efficiently in primary rhesus cells. This was a subtype AE SHIV that naturally contained His at Env375. Replacement of wildtype Env375 residues by Trp, Tyr, Phe or His in the other nine SHIVs led to efficient replication in rhesus CD4+ T cells in vitro and in vivo. Nine SHIVs containing optimized Env375 alleles were grown large-scale in primary rhesus CD4+ T cells to serve as challenge stocks in preclinical prevention trials. These virus stocks were genetically homogeneous, native-like in Env antigenicity and tier-2 neutralization sensitivity, and transmissible by rectal, vaginal, penile, oral or intravenous routes. To facilitate future SHIV constructions, we engineered a simplified second-generation design scheme and validated it in RMs. Overall, our findings demonstrate that SHIVs bearing primary Envs with bulky aromatic substitutions at Env375 consistently replicate in RMs, recapitulating many features of HIV-1 infection in humans. Such SHIVs are efficiently transmitted by mucosal routes common to HIV-1 infection and can be used to test vaccine efficacy in preclinical monkey trials. Importance SHIV infection of Indian rhesus macaques is an important animal model for studying HIV-1 transmission, prevention, immunopathogenesis and cure. Such research is timely, given recent progress with active and passive immunization and novel approaches to HIV-1 cure. Given the multifaceted roles of HIV-1 Env in cell tropism and virus entry, and as a target for neutralizing and non-neutralizing antibodies, Envs selected for SHIV construction are of paramount importance. Until recently, it has been impossible to strategically design SHIVs bearing clinically relevant Envs that replicate consistently in monkeys. This changed with the discovery that bulky aromatic substitutions at residue Env375 confer enhanced affinity to rhesus CD4. Here, we show that 10 new SHIVs bearing primary HIV-1 Envs with residue 375 substitutions replicated efficiently in RMs and could be transmitted efficiently across rectal, vaginal, penile and oral mucosa. These findings suggest an expanded role for SHIVs as a model of HIV-1 infection.

scholarly journals SARS-CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients

2021 ◽  
Author(s):  
Vimvara Vacharathit ◽  
Pakorn Aiewsakun ◽  
Suwimon Manopwisedjaroen ◽  
Chanya Srisaowakarn ◽  
Thanida Laopanupong ◽  
...  
Keyword(s):  
Low Income ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Mitigation Strategies ◽  
Low Income Countries ◽  
Live Virus ◽  
Neutralizing Capacity ◽  
Need To Evaluate ◽  
Beijing China ◽  
Spike Sequence

Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine- and infection- induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decisionmakers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.

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