Immunotherapies and immunomodulatory approaches in clinical trials - a mini review.

The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.

Advances in therapeutic and managemental approaches of bovine mastitis: a comprehensive review.

Mastitis (intramammary inflammation) caused by infectious pathogens is still considered a devastating condition of dairy animals affecting animal welfare as well as economically incurring huge losses to the dairy industry by means of decreased production performance and increased culling rates. Bovine mastitis is the inflammation of the mammary glands/udder of bovines, caused by bacterial pathogens, in most cases. Routine diagnosis is based on clinical and subclinical forms of the disease. This underlines the significance of early and rapid identification/detection of etiological agents at the farm level, for which several diagnostic techniques have been developed. Therapeutic regimens such as antibiotics, immunotherapy, bacteriocins, bacteriophages, antimicrobial peptides, probiotics, stem cell therapy, native secretory factors, nutritional, dry cow and lactation therapy, genetic selection, herbs, and nanoparticle technology-based therapy have been evaluated for their efficacy in the treatment of mastitis. Even though several strategies have been developed over the years for the purpose of managing both clinical and subclinical forms of mastitis, all of them lacked the efficacy to eliminate the associated etiological agent when used as a monotherapy. Further, research has to be directed towards the development of new therapeutic agents/techniques that can both replace conventional techniques and also solve the problem of emerging antibiotic resistance. The objective of the present review is to describe the etiological agents, pathogenesis, and diagnosis in brief along with an extensive discussion on the advances in the treatment and management of mastitis, which would help safeguard the health of dairy animals.

Bovine brucellosis - a comprehensive review.

Brucellosis is a zoonotic disease of great animal welfare and economic implications worldwide known since ancient times. The emergence of brucellosis in new areas as well as transmission of brucellosis from wild and domestic animals is of great significance in terms of new epidemiological dimensions. Brucellosis poses a major public health threat by the consumption of non-pasteurized milk and milk products produced by unhygienic dairy farms in endemic areas. Regular and meticulous surveillance is essentially required to determine the true picture of brucellosis especially in areas with continuous high prevalence. Additionally, international migration of humans, animals and trade of animal products has created a challenge for disease spread and diagnosis in non-endemic areas. Isolation and identification remain the gold standard test, which requires expertise. The advancement in diagnostic strategies coupled with screening of newly introduced animals is warranted to control the disease. Of note, the diagnostic value of miRNAs for appropriate detection of B. abortus infection has been shown. The most widely used vaccine strains to protect against Brucella infection and related abortions in cattle are strain 19 and RB51. Moreover, it is very important to note that no vaccine, which is highly protective, safe and effective is available either for bovines or human beings. Research results encourage the use of bacteriophage lysates in treatment of bovine brucellosis. One Health approach can aid in control of this disease, both in animals and man.

Plant-based vaccines and antibodies to combat COVID-19: current status and prospects.

Globally, researchers are undertaking significant efforts to design and develop effective vaccines, therapeutics, and antiviral drugs to curb the spread of coronavirus disease 2019 (COVID-19). Plants have been used for the production of vaccines, monoclonal antibodies, immunomodulatory proteins, drugs, and pharmaceuticals via molecular farming/transient expression system and are considered as bioreactors or factories for their bulk production. These biological products are stable, safe, effective, easily available, and affordable. Plant molecular farming could facilitate rapid production of biologics on an industrial scale, and has the potential to fulfill emergency demands, such as in the present situation of the COVID-19 pandemic. This article aims to describe the methodology and basics of plant biopharming, in addition to its prospective applications for developing effective vaccines and antibodies to counter COVID-19.

COVID-19 in the elderly people and advances in vaccination approaches.

The rapid worldwide spread of the COVID-19 pandemic, caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in tens of millions of infections and over one million deaths. SARS-CoV-2 infection affects all age groups; however, those over 60 years old are affected more severely. Moreover, pre-existing co-morbidities result in higher COVID-19-associated mortality in the geriatric population. This article highlights the associated risk factors of SARS-CoV-2 infection in older people and progress in developing COVID-19 vaccines, especially for efficient vaccination of the older population. There is also a summary of immunomodulatory and immunotherapeutic approaches to ameliorate the outcome of COVID-19 in older individuals.

BCG vaccine: a hope to control COVID-19 pandemic amid crisis.

COVID-19 caused by the virus SARS-CoV-2 has gripped essentially all countries in the world, and has infected millions and killed hundreds of thousands of people. Several innovative approaches are in development to restrain the spread of SARS-CoV-2. In particular, BCG, a vaccine against tuberculosis (TB), is being considered as an alternative therapeutic modality. BCG vaccine is known to induce both humoral and adaptive immunities, thereby activating both nonspecific and cross-reactive immune responses in the host, which combined could effectively resist other pathogens including SARS-CoV-2. Notably, some studies have revealed that SARS-CoV-2 infectivity, case positivity, and mortality rate have been higher in countries that have not adopted BCG vaccination than in countries that have done so. This review presents an overview of the concepts underlying BCG vaccination and its nonspecific immuological effects and protection, resulting in 'trained immunity' and potential utility for resisting COVID-19.

Coronavirus disease 2019 (COVID-19) in domestic animals and wildlife: advances and prospects in the development of animal models for vaccine and therapeutic research.

SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), is suspected to have been first contracted via animal-human interactions; it has further spread across the world by efficient human-to-human transmission. Recent reports of COVID-19 in companion animals (dogs and cats) and wild carnivores such as tigers have created a dilemma regarding its zoonotic transmission. Although in silico docking studies, sequence-based computational studies, and experimental studies have shown the possibility of SARS-CoV-2 infection and transmission in cats, ferrets, and other domestic/wild animals, the results are not conclusive of infection under natural conditions. Identifying the potential host range of SARS-CoV-2 will not only help prevent the possibility of human-to-animal and animal-to-human transmission but also assist in identifying efficient animal models that can mimic the clinical symptoms, transmission potential, and pathogenesis of the disease. Such an efficient animal model will accelerate the process of development and evaluation of vaccines, immunotherapeutics, and other remedies for SARS-CoV-2.

Antibody-based immunotherapeutics and use of convalescent plasma to counter COVID-19: advances and prospects.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has spread to several countries globally. Currently, there is no specific drug or vaccine available for managing COVID-19. Antibody-based immunotherapeutic strategies using convalescent plasma, monoclonal antibodies (mAbs), neutralizing antibodies (NAbs), and intravenous immunoglobulins have therapeutic potential. AREAS COVERED: This review provides the current status of the development of various antibody-based immunotherapeutics such as convalescent plasma, mAbs, NAbs, and intravenous immunoglobulins against COVID-19. The review also highlights their advantages, disadvantages, and clinical utility for the treatment of COVID-19 patients. EXPERT OPINION: In a pandemic situation such as COVID-19, the development of new drugs should focus on and expedite the strategies where safety and efficacy are proven. Antibody-based immunotherapeutic approaches such as convalescent plasma, intravenous immunoglobulins, and mAbs have a proven record of safety and efficacy and are in use for decades. Some of them are already being used to manage COVID-19 patients and found to be useful. However, the mAbs with virus neutralization potential is the need of the hour during this COVID-19 pandemic to be more specific and virus targeted. The research and investment need to be accelerated to bring them into clinical use for prophylactic and therapeutic purposes against COVID-19.

COVID-19 - Recent advancements in identifying novel vaccine candidates and current status of upcoming SARS-CoV-2 vaccines.

The COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly. To date, countries have relied on the prevention of the disease through isolation, quarantine, and clinical care of affected individuals. However, studies on the roles of asymptomatic and mildly infected subjects in disease transmission, use of antiviral drugs, and vaccination of the general population will be very important for mitigating the effects of the eventual return of this pandemic. Initial investigations are ongoing to evaluate antigenic structures of SARS-CoV-2 and the immunogenicity of vaccine candidates. There also is a need to comprehensively compile the details of previous studies on SARS-related vaccines that can be extrapolated to identify potent vaccine targets for developing COVID-19 vaccines. This review aims to analyze previous studies, current status, and future possibilities for producing SARS-CoV-2 vaccines.

COVID-19: animals, veterinary and zoonotic links.

Coronavirus disease 2019 (COVID-19), has spread over 210 countries and territories beyond China shortly. On February 29, 2020, the World Health Organization (WHO) denoted it in a high-risk category, and on March 11, 2020, this virus was designated pandemic, after its declaration being a Public Health International Emergency on January 30, 2020. World over high efforts are being made to counter and contain this virus. The COVID-19 outbreak once again proves the potential of the animal-human interface to act as the primary source of emerging zoonotic diseases. Even though the circumstantial evidence suggests the possibility of an initial zoonotic emergence, it is too early to confirm the role of intermediate hosts such as snakes, pangolins, turtles, and other wild animals in the origin of SARS-CoV-2, in addition to bats, the natural hosts of multiple coronaviruses such as SARS-CoV and MERS-CoV. The lessons learned from past episodes of MERS-CoV and SARS-CoV are being exploited to retort this virus. Best efforts are being taken up by worldwide nations to implement effective diagnosis, strict vigilance, heightened surveillance, and monitoring, along with adopting appropriate preventive and control strategies. Identifying the possible zoonotic emergence and the exact mechanism responsible for its initial transmission will help us to design and implement appropriate preventive barriers against the further transmission of SARS-CoV-2. This review discusses in brief about the COVID-19/SARS-CoV-2 with a particular focus on the role of animals, the veterinary and associated zoonotic links along with prevention and control strategies based on One-health approaches.

Etiology, epidemiology, pathology, and advances in diagnosis, vaccine development, and treatment of Gallibacterium anatis infection in poultry: a review.

Gallibacterium anatis is a Gram-negative bacterium of the Pasteurellaceae family that resides normally in the respiratory and reproductive tracts in poultry. It is a major cause of oophoritis, salpingitis, and peritonitis, decreases egg production and mortality in hens thereby severely affecting animal welfare and overall productivity by poultry industries across Europe, Asia, America, and Africa. In addition, it has the ability to infect wider host range including domesticated and free-ranging avian hosts as well as mammalian hosts such as cattle, pigs and human. Evaluating the common virulence factors including outer membrane vesicles, fimbriae, capsule, metalloproteases, biofilm formation, hemagglutinin, and determining novel factors such as the RTX-like toxin GtxA, elongation factor-Tu, and clustered regularly interspaced short palindromic repeats (CRISPR) has pathobiological, diagnostic, prophylactic, and therapeutic significance. Treating this bacterial pathogen with traditional antimicrobial drugs is discouraged owing to the emergence of widespread multidrug resistance, whereas the efficacy of preventing this disease by classical vaccines is limited due to its antigenic diversity. It will be necessary to acquire in-depth knowledge on important virulence factors, pathogenesis and, concerns of rising antibiotic resistance, improvised treatment regimes, and novel vaccine candidates to effectively tackle this pathogen. This review substantially describes the etio-epidemiological aspects of G. anatis infection in poultry, and updates the recent development in understanding the pathogenesis, organism evolution and therapeutic and prophylactic approaches to counter G. anatis infection for safeguarding the welfare and health of poultry.

Technological interventions and advances in the diagnosis of intramammary infections in animals with emphasis on bovine population-a review.

Mastitis, an inflammation of the udder, is a challenging problem in dairy animals accounting for high economic losses. Disease complexity, degree of economic losses and increasing importance of the dairy industries along with public health concerns envisages devising appropriate diagnostics of mastitis, which can offer rapid, accurate and confirmatory diagnosis. The various diagnostic tests of mastitis have been divided into general or phenotypic and specific or genotypic tests. General or phenotypic tests are those that identify general alterations, which are not specific to any pathogen. Genotypic tests are specific, hence confirmatory for diagnosis of mastitis and include specific culture, polymerase chain reaction (PCR) and its various versions (e.g. qRT-PCR), loop-mediated isothermal amplification, lateral flow assays, nucleotide sequencing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and other molecular diagnostic methods. However, for highly specific and confirmatory diagnosis, pure cultures still provide raw materials for more sophisticated diagnostic technological interventions like PCR and nucleotide sequencing. Diagnostic ability of like infra-red thermography (IRT) has been shown to be similar to California mastitis test and also differentiates clinical mastitis from subclinical mastitis cases. As such, IRT can become a convenient and portable diagnostic tool. Of note, magnetic nanoparticles-based colorimetric biosensor assay was developed by using for instance proteolytic activity of plasmin or anti-S. aureus antibody. Last but not least, microRNAs have been suggested to be potential biomarkers for diagnosing bovine mastitis. This review summarizes the various diagnostic tests available for detection of mastitis including diagnosis through general and specific technological interventions and advances.

Contagious caprine pleuropneumonia - a comprehensive review.

Contagious caprine pleuropneumonia (CCPP) is a serious disease of goats, occasionally sheep and wild ruminants, caused by Mycoplasma capricolum subspecies capripneumoniae (Mccp). The disease is characterized by severe serofibrinous pleuropneumonia, very high morbidity (∼100%), and mortality (80-100%). CCPP affects goats in more than 40 countries of the world thereby posing a serious threat to goat farming around the globe. The characteristic clinical signs of CCPP are severe respiratory distress associated with sero-mucoid nasal discharge, coughing, dyspnea, pyrexia, pleurodynia, and general malaise. In later stages, severe lobar fibrinous pleuropneumonia, profuse fluid accumulation in pleural cavity, severe congestion of lungs and adhesion formation is observed. Mycoplasmal antigen interactions with host immune system and its role in CCPP pathogenesis are not clearly understood. CCPP is not a zoonotic disease. Diagnosis has overcome cumbersome and lengthy conventional tests involving culture, isolation, and identification by advanced serological (LAT, cELISA) or gene-based amplification of DNA (PCR, RFLP, and hybridization) and sequencing. The latex agglutination test (LAT) is rapid, simple, and better test for field and real-time diagnosis applicable to whole blood or serum and is more sensitive than the CFT and easier than the cELISA. Moreover, the studies on antibiotic sensitivity and exploration of novel antibiotics (fluoroquinolones, macrolides) can help in better therapeutic management besides preventing menace of antibiotic resistance. Re-visiting conventional prophylactic measures focussing on developing novel strain-based or recombinant vaccines using specific antigens (capsular or cellular) should be the most important strategy for controlling the disease worldwide.