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Viruses May 2024COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly...
Sequential Infection with Influenza A Virus Followed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Leads to More Severe Disease and Encephalitis in a Mouse Model of COVID-19.
COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection ('twinfection') is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.
Topics: Animals; COVID-19; Mice; Disease Models, Animal; SARS-CoV-2; Influenza A virus; Orthomyxoviridae Infections; Mice, Transgenic; Angiotensin-Converting Enzyme 2; Humans; Coinfection; Lung; Encephalitis, Viral; Influenza Vaccines; Female; Immunity, Innate
PubMed: 38932155
DOI: 10.3390/v16060863 -
Viruses May 2024This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years.
OBJECTIVE
This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years.
METHODS
This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42).
RESULTS
All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed.
CONCLUSION
The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.
Topics: Humans; Male; Female; Vietnam; Child; Chickenpox Vaccine; Antibodies, Viral; Infant; Vaccines, Attenuated; Child, Preschool; Vaccination; Chickenpox; Immunogenicity, Vaccine; Herpesvirus 3, Human; Southeast Asian People
PubMed: 38932134
DOI: 10.3390/v16060841 -
Viruses May 2024Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges... (Review)
Review
Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines.
Topics: Animals; Swine; Viral Vaccines; Swine Diseases; Virus Diseases; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated; Viruses
PubMed: 38932126
DOI: 10.3390/v16060833 -
Viruses May 2024When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic...
When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic manipulation and may include point mutations, codon and gene deletions, and genome rearrangements. Attenuation typically involves the reduction in virus replication, due to direct effects on viral structural and replicative machinery or viral factors that antagonize host defense or cause disease. However, attenuation must balance reduced replication and immunogenic antigen expression. In the present study, we explored a new approach in order to discover attenuating mutations. Specifically, we used protein structure modeling and computational methods to identify amino acid substitutions in the RSV nonstructural protein 1 (NS1) predicted to cause various levels of structural perturbation. Twelve different mutations predicted to alter the NS1 protein structure were introduced into infectious virus and analyzed in cell culture for effects on viral mRNA and protein expression, interferon and cytokine expression, and caspase activation. We found the use of structure-based machine learning to predict amino acid substitutions that reduce the thermodynamic stability of NS1 resulted in various levels of loss of NS1 function, exemplified by effects including reduced multi-cycle viral replication in cells competent for type I interferon, reduced expression of viral mRNAs and proteins, and increased interferon and apoptosis responses.
Topics: Humans; Machine Learning; Viral Nonstructural Proteins; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Virus Replication; Vaccines, Attenuated; Respiratory Syncytial Virus Infections; Amino Acid Substitution; Mutation; Cell Line
PubMed: 38932114
DOI: 10.3390/v16060821 -
Microorganisms Jun 2024serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic...
serovar Gallinarum biovar Gallinarum (SG) causes fowl typhoid, a notifiable infectious disease in poultry. However, the pathogenic mechanism of SG-induced systemic infection in chickens remains unclear. Thioredoxin reductase (TrxB) is a redox protein crucial for regulating various enzyme activities in serovar, but the role in SG-induced chicken systemic infection has yet to be determined. Here, we constructed a mutant SG strain lacking the gene (::Cm) and used chicken embryo inoculation and chicken oral infection to investigate the role of gene in the pathogenicity of SG. Our results showed that ::Cm exhibited no apparent differences in colony morphology and growth conditions but exhibited reduced tolerance to HO and increased resistance to bile acids. In the chicken embryo inoculation model, there was no significant difference in the pathogenicity of ::Cm and wild-type (WT) strains. In the chicken oral infection, the WT-infected group exhibited typical clinical symptoms of fowl typhoid, with complete mortality between days 6 and 9 post infection. In contrast, the ::Cm group showed a 100% survival rate, with no apparent clinical symptoms or pathological changes observed. The viable bacterial counts in the liver and spleen of the ::Cm-infected group were significantly reduced, accompanied by decreased expression of cytokines and chemokines (IL-1β, IL-6, IL-12, CXCLi1, TNF-α, and IFN-γ), which were significantly lower than those in the WT group. These results show that the pathogenicity of the -deficient strain was significantly attenuated, indicating that the gene is a crucial virulence factor in SG-induced systemic infection in chickens, suggesting that may become a potentially effective target for controlling and preventing SG infection in chickens.
PubMed: 38930562
DOI: 10.3390/microorganisms12061180 -
Animals : An Open Access Journal From... Jun 2024The QXL87 live attenuated vaccine strain for infectious bronchitis represents the first approved QX type (GI-19 lineage) vaccine in China. This strain was derived from...
The QXL87 live attenuated vaccine strain for infectious bronchitis represents the first approved QX type (GI-19 lineage) vaccine in China. This strain was derived from the parental strain CK/CH/JS/2010/12 through continuous passage in SPF chicken embryos. To elucidate the molecular mechanism behind its attenuation, whole-genome sequencing was conducted on both the parental and attenuated strains. Analysis revealed 145 nucleotide mutations in the attenuated strain, leading to 48 amino acid mutations in various proteins, including Nsp2 (26), Nsp3 (14), Nsp4 (1), S (4), 3a (1), E (1), and N (1). Additionally, a frameshift mutation caused by a single base insertion in the ORFX resulted in a six-amino-acid extension. Subsequent comparison of post-translational modification sites, protein structure, and protein-protein binding sites between the parental and attenuated strains identified three potential virulence genes: Nsp2, Nsp3, and S. The amino acid mutations in these proteins not only altered their conformation but also affected the distribution of post-translational modification sites and protein-protein interaction sites. Furthermore, three potential functional mutation sites-P106S, A352T, and L472F, all located in the Nsp2 protein-were identified through PROVEAN, PolyPhen, and I-Mutant. Overall, our findings suggest that Nsp2, Nsp3, and S proteins may play a role in modulating IBV pathogenicity, with a particular focus on the significance of the Nsp2 protein. This study contributes to our understanding of the molecular mechanisms underlying IBV attenuation and holds promise for the development of safer live attenuated IBV vaccines using reverse genetic approaches.
PubMed: 38929403
DOI: 10.3390/ani14121784 -
Communicable Diseases Intelligence... Jun 2024This report from the Australian Rotavirus Surveillance Program describes the circulating rotavirus genotypes identified in children and adults during the period 1...
This report from the Australian Rotavirus Surveillance Program describes the circulating rotavirus genotypes identified in children and adults during the period 1 January to 31 December 2022. After two years of a lower number of stool samples received as a result of the coronavirus disease 2019 (COVID-19) pandemic, this reporting period saw the highest number of samples received since the 2017 surveillance period, with samples received from all states and territories. During this period, 1,379 faecal specimens had been referred for rotavirus G- and P- genotype analysis, of which 1,276 were confirmed as rotavirus positive. In total, 1,119/1,276 were identified as wildtype rotavirus, 155/1,276 identified as the Rotarix vaccine strain and 2/1,276 that could not be confirmed as vaccine or wildtype due to sequencing failure. Whilst G12P[8] was the dominant genotype nationally among wildtype samples (28.2%; 315/1,119), multiple genotypes were identified at similar frequencies including G9P[4] (22.3%; 249/1,119) and G2P[4] (20.3%; 227/1,119). Geographical differences in genotype distribution were observed, largely driven by outbreaks reported in some jurisdictions. Outbreaks and increased reports of rotavirus disease were reported in the Northern Territory, Queensland, and New South Wales. A small number of unusual genotypes, potentially zoonotic in nature, were identified, including: G8P[14]; G10[14]; caninelike G3P[3]; G6P[9]; and G11P[25]. Ongoing rotavirus surveillance is crucial to identify changes in genotypic patterns and to provide diagnostic laboratories with quality assurance by reporting incidences of wildtype, vaccine-like, or false positive rotavirus results.
Topics: Humans; Rotavirus Infections; Rotavirus; Australia; Genotype; Feces; Rotavirus Vaccines; Child, Preschool; Infant; Child; Adult; COVID-19; SARS-CoV-2; Adolescent; Female; Male; Disease Outbreaks; Vaccines, Attenuated; Infant, Newborn; Annual Reports as Topic; Epidemiological Monitoring; Middle Aged
PubMed: 38926653
DOI: 10.33321/cdi.2024.48.27 -
Life Sciences Jun 2024SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host... (Review)
Review
SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2.
PubMed: 38925222
DOI: 10.1016/j.lfs.2024.122861 -
Journal of Medical Virology Jun 2024Globally, Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children under 5 years old, with Pakistan having the highest rates of RVA-related...
Molecular characterization of rotavirus indicates predominance of G9P[4] genotype among children with acute gastroenteritis: First report after vaccine introduction in Pakistan.
Globally, Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children under 5 years old, with Pakistan having the highest rates of RVA-related morbidity and mortality. The current study aims to determine the genetic diversity of rotavirus and evaluate the impact of Rotarix-vaccine introduction on disease epidemiology in Pakistan. A total of 4749 children, hospitalized with acute gastroenteritis between 2018 and 2020, were tested at four hospitals in Lahore and Karachi. Of the total, 19.3% (918/4749) cases were tested positive for RVA antigen, with the positivity rate varying annually (2018 = 22.7%, 2019 = 14.4%, 2020 = 20.9%). Among RVA-positive children, 66.3% were under 1 year of age. Genotyping of 662 enzyme-linked immuno sorbent assay-positive samples revealed the predominant genotype as G9P[4] (21.4%), followed by G1P[8] (18.9%), G3P[8] (11.4%), G12P[6] (8.7%), G2P[4] (5.7%), G2P[6] (4.8%), and 10.8% had mixed genotypes. Among vaccinated children, genotypes G9P[4] and G12P[6] were more frequently detected, whereas a decline in G2P[4] was observed. Phylogenetic analysis confirmed the continued circulation of indigenous genotypes detected earlier in the country except G9 and P[6] strains. Our findings highlight the predominance of G9P[4] genotype after the vaccine introduction thus emphasizing continual surveillance to monitor the disease burden, viral diversity, and their impact on control of rotavirus gastroenteritis in children.
Topics: Humans; Rotavirus; Gastroenteritis; Rotavirus Infections; Genotype; Rotavirus Vaccines; Infant; Child, Preschool; Pakistan; Female; Male; Vaccines, Attenuated; Phylogeny; Genetic Variation; Feces; Acute Disease
PubMed: 38924137
DOI: 10.1002/jmv.29761 -
Pathogens (Basel, Switzerland) May 2024African horse sickness is a devastating viral disease of equids. It is transmitted by biting midges of the genus with mortalities reaching over 90% in naïve horses. It... (Review)
Review
African horse sickness is a devastating viral disease of equids. It is transmitted by biting midges of the genus with mortalities reaching over 90% in naïve horses. It is endemic to sub-Saharan Africa and is seasonally endemic in many parts of southern Africa. However, outbreaks in Europe and Asia have occurred that caused significant economic issues. There are attenuated vaccines available for control of the virus but concerns regarding the safety and efficacy means that alternatives are sought. One promising alternative is the use of virus-like particles in vaccine preparations, which have the potential to be safer and more efficacious as vaccines against African horse sickness. These particles are best made in a complex, eukaryotic system, but due to technical challenges, this may cause significant economic strain on the developing countries most affected by the disease. Therefore, this review also summarises the success so far, and potential, of recombinant protein expression in plants to reduce the economic strain of production.
PubMed: 38921755
DOI: 10.3390/pathogens13060458