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With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and production efficiency. Notably, biotechnology-based approaches have fueled rapid advances in biological research, including (a) genetic manipulation in poultry breeding to improve the growth and egg production traits and disease resistance, (b) rapid identification of infectious agents using DNA-based approaches, (c) inclusion of natural and synthetic feed additives to poultry diets to enhance their nutritional value and maximize feed utilization by birds, and (d) production of biological products such as vaccines and various types of immunostimulants to increase the defensive activity of the immune system against pathogenic infection. Indeed, managing both existing and newly emerging infectious diseases presents a challenge for poultry production. However, recent strides in vaccine technology are demonstrating significant promise for disease prevention and control. This review focuses on the evolving applications of biotechnology aimed at enhancing vaccine immunogenicity, efficacy, stability, and delivery. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity. [ABSTRACT FROM AUTHOR]

Influenza B viruses (IBV) circulate annually, with young children, the elderly and immunocompromised individuals being at high risk. Yearly vaccinations are recommended to protect against seasonally influenza viruses, including IBV. Live attenuated influenza vaccines (LAIV) provide the unique opportunity for direct exposure to the antigenically variable surface glycoproteins as well as the more conserved internal components. Ideally, LAIV Master Donor Viruses (MDV) should accurately reflect seasonal influenza strains. Unfortunately, the continuous evolution of IBV have led to significant changes in conserved epitopes compared to the IBV MDV based on B/Ann Arbor/1/1966 strain. Here, we propose a recent influenza B/Brisbane/60/2008 as an efficacious MDV alternative, as its internal viral proteins more accurately reflect those of circulating IBV strains. We introduced the mutations responsible for the temperature sensitive (ts), cold adapted (ca) and attenuated (att) phenotype of B/Ann Arbor/1/1966 MDV LAIV into B/Brisbane/60/2008 to generate a new MDV LAIV. In vitro and in vivo analysis demonstrated that the mutations responsible of the ts, ca, and att phenotype of B/Ann Arbor/1/1966 MDV LAIV were able to infer the same phenotype to B/Brisbane/60/2008, demonstrating its potential as a new MDV for the development of LAIV to protect against contemporary IBV strains. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a recently emerged, novel human coronavirus responsible for the currently ongoing COVID-19 pandemic. Recombination is a well-known evolutionary strategy of coronaviruses, which may frequently result in significant genetic alterations, such as deletions throughout the genome. In this study we identified a co-infection with two genetically different SARS-CoV-2 viruses within a single patient sample via amplicon-based next generation sequencing in Hungary. The recessive strain contained an 84 base pair deletion in the receptor binding domain of the Spike protein gene and was found to be gradually displaced by a dominant non-deleterious variant over-time. We have identified the region of the RBD that is affected by the mutation, created homology models of the RBDΔ84 mutant, and based on the available experimental data and calculations, we propose that the mutation has a deteriorating effect on the binding of RBD to the ACE2 receptor, which results in the negative selection of this variant. Extending the sequencing capacity toward the discovery of emerging recombinant or deleterious strains may facilitate the early recognition of novel strains with altered phenotypic attributes and understand key elements of Spike protein evolution. Such studies may greatly contribute to future therapeutic research and general understanding of genomic processes of the virus. [ABSTRACT FROM AUTHOR]

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars. [ABSTRACT FROM AUTHOR]

The poxvirus, myxoma virus (MYXV) has shown efficacy as an oncolytic virus (OV) in some cancer models. However, MYXV replication within murine cancer models and spontaneous canine sarcomas is short-lived. In mice, successful treatment of tumors requires frequent injections with MYXV. We hypothesize that treatment of cancer with a recombinant MYXV that promotes apoptosis could improve the efficacy of MYXV. The orfC gene of walleye dermal sarcoma virus (WDSV), which induces apoptosis, was recombined into the MYXV genome (MYXVorfC). A marked increase in apoptosis was observed in cells infected with MYXVorfC. To ensure that expression of WDSV orfC by MYXV does not potentiate the pathogenesis of MYXV, we evaluated the effects of MYXVorfC inoculation in the only known host of MYXV, New Zealand white rabbits. Virus dissemination in rabbit tissues was similar for MYXVorfC and MYXV. Virus titers recovered from tissues were lower in MYXVorfC-infected rabbits as compared to MYXV-infected rabbits. Importantly, rabbits infected with MYXVorfC had a delayed onset of clinical signs and a longer median survival time than rabbits infected with MYXV. This study indicates that MYXVorfC is attenuated and suggests that MYXVorfC will be safe to use as an OV therapy in future studies. [ABSTRACT FROM AUTHOR]

Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs. [ABSTRACT FROM AUTHOR]

Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, such as the adaptation of viruses to replicate at low temperatures. These approaches require an extensive investment of time and resources before identifying potential vaccine candidates that can be safely implemented as LAIV to protect humans. In addition, the mechanism of attenuation of these vaccines is poorly understood in some cases. Importantly, LAIV are more efficacious than inactivated vaccines because their ability to mount efficient innate and adaptive humoral and cellular immune responses. Therefore, the design of potential LAIV based on known properties of viral proteins appears to be a highly appropriate option for the treatment of influenza viral infections. For that, the viral RNA synthesis machinery has been a research focus to identify key amino acid substitutions that can lead to viral attenuation and their use in safe, immunogenic, and protective LAIV. In this review, we discuss the potential to manipulate the influenza viral RNA-dependent RNA polymerase (RdRp) complex to generate attenuated forms of the virus that can be used as LAIV for the treatment of influenza viral infections, one of the current and most effective prophylactic options for the control of influenza in humans. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity., Competing Interests: The authors declare no conflict of interest.