Gyrolab Immunoassays: Miniaturization, Automation, and Integration into a Rapid Workflow.

Gyrolab® is an open immunoassay platform that automates the complete immunoassay protocol in a microfluidic disc. The column profiles generated with Gyrolab immunoassays are used to gain more information about biomolecular interactions that can be useful in assay development or quantify analytes in samples. Gyrolab immunoassays can be used to cover a broad concentration range and diversity of matrices in applications ranging from biomarker monitoring, pharmacodynamics and pharmacokinetics studies, to bioprocess development in many areas, including therapeutic antibodies, vaccines, and cell and gene therapy.This chapter is an overview of Gyrolab technology, including system components and the assay development workflow, including the process of selecting affinity reagents, Gyrolab Bioaffy CDs, and assay conditions to optimize immunoassays. Two case studies are included. The first involves an assay for the humanized antibody pembrolizumab used in cancer immunotherapy that can generate data for pharmacokinetics studies. The second case study involves quantification of the biomarker and biotherapeutic interleukin-2 (IL-2) in human serum and buffer. IL-2 has been implicated in the cytokine storm associated with COVID-19, and cytokine release syndrome (CRS), which can occur during chimeric antigen receptor T cell (CART) therapy used in treating cancer. These molecules also have therapeutic relevance in combination.

COVID-19 management landscape: A need for an affordable platform to manufacture safe and efficacious biotherapeutics and prophylactics for the developing countries.

To gain world-wide control over COVID-19 pandemic, it is necessary to have affordable and accessible vaccine and monoclonal antibody technologies across the globe. In comparison to the western countries, Asian and African countries have less percentage of vaccination done which warrants urgent attention. Global manufacturer production capacities, dependency on advanced nations for the supply of vaccines or the raw material, national economy, limited research facilities, and logistics could be the factors. This review article elaborates the existing therapeutic and prophylactic strategies available for COVID-19, currently adopted vaccine and monoclonal antibody platforms for SARS-CoV-2 along with the approaches to bridge the gap prevailing in the challenges faced by low- and middle-income countries. We believe adoption of yeast-derived P. pastoris technology can help in developing safe, proven, easy to scale-up, and affordable recombinant vaccine or monoclonal antibodies against SARS-CoV-2. This platform has the advantage of not requiring a dedicated or specialized facility making it an affordable option using existing manufacturing facilities, without significant additional capital investments. Besides, the technology platform of multiantigen vaccine approach and monoclonal antibody cocktail will serve as effective weapons to combat the threat posed by the SARS-CoV-2 variants. Successful development of vaccines and monoclonal antibodies using such a technology will lead to self-sufficiency of these nations in terms of availability of vaccines and monoclonal antibodies.

Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery.

Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide-drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.

Transchromosomic bovines-derived broadly neutralizing antibodies as potent biotherapeutics to counter important emerging viral pathogens with a special focus on SARS-CoV-2, MERS-CoV, Ebola, Zika, HIV-1, and influenza A virus.

Historically, passive immunotherapy is an approved approach for protecting and treating humans against various diseases when other alternative therapeutic options are unavailable. Human polyclonal antibodies (hpAbs) can be made from convalescent human donor serum, although it is considered limited due to pandemics and the urgent requirement. Additionally, polyclonal antibodies (pAbs) could be generated from animals, but they may cause severe immunoreactivity and, once "humanized," may have lower neutralization efficiency. Transchromosomic bovines (TcBs) have been developed to address these concerns by creating robust neutralizing hpAbs, which are useful in preventing and/or curing human infections in response to hyperimmunization with vaccines holding adjuvants and/or immune stimulators over an extensive period. Unlike other animal-derived pAbs, potent hpAbs could be promptly produced from TcB in large amounts to assist against an outbreak scenario. Some of these highly efficacious TcB-derived antibodies have already neutralized and blocked diseases in clinical studies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB-185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovine-derived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARS-CoV-2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed.

To PEGylate or not to PEGylate: Immunological properties of nanomedicine's most popular component, polyethylene glycol and its alternatives.

Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.

Biomaterials, biological molecules, and polymers in developing vaccines.

Vaccines have been used to train the immune system to recognize pathogens, and prevent and treat diseases, such as cancer, for decades. However, there are continuing challenges in their manufacturing, large-scale production, and storage. Some of them also show suboptimal immunogenicity, requiring additional adjuvants and booster doses. As an alternate vaccination strategy, a new class of biomimetic materials with unique functionalities has emerged in recent years. Here, we explore the current bioengineering techniques that make use of hydrogels, modified polymers, cell membranes, self-assembled proteins, virus-like particles (VLPs), and nucleic acids to deliver and develop biomaterial-based vaccines. We also review design principles and key regulatory issues associated with their development. Finally, we critically assess their limitations, explore approaches to overcome these limitations, and discuss potential future applications for clinical translation.