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Microbial Biotechnology Jul 2024Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and...
Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC-Linker-COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO-26 K equivalent (COE) of the epidemic strain PEDV-AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168-CLE, B. subtilis 168, or phosphate-buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL-4, IFN-γ) levels in the B. subtilis 168-CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168-CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.
Topics: Porcine epidemic diarrhea virus; Animals; Bacillus subtilis; Spores, Bacterial; Mice; Antibodies, Viral; Swine; Viral Vaccines; Coronavirus Infections; Swine Diseases; Antigens, Viral; Administration, Oral; Cytokines; Immunoglobulin G; Mice, Inbred BALB C; Female; Cell Surface Display Techniques; Spike Glycoprotein, Coronavirus
PubMed: 38953907
DOI: 10.1111/1751-7915.14518 -
Oncotarget Jul 2024
Correction: BALB/c mice immunized with a combination of virus-like particles incorporating Kaposi sarcoma-associated herpesvirus (KSHV) envelope glycoproteins gpK8.1, gB, and gH/gL induced comparable serum neutralizing antibody activity to UV-inactivated KSHV.
Topics: Animals; Herpesvirus 8, Human; Mice; Mice, Inbred BALB C; Antibodies, Neutralizing; Viral Envelope Proteins; Antibodies, Viral; Vaccines, Virus-Like Particle; Humans; Ultraviolet Rays
PubMed: 38953905
DOI: 10.18632/oncotarget.28600 -
The Journal of Experimental Medicine Sep 2024Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin...
Gain-of-function mutations in STING cause STING-associated vasculopathy with onset in infancy (SAVI) characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease. Here, we report and characterize a novel STING variant (F269S) identified in a SAVI patient. Single-cell transcriptomics of patient bone marrow revealed spontaneous activation of interferon (IFN) and inflammatory pathways across cell types and a striking prevalence of circulating naïve T cells was observed. Inducible STING F269S expression conferred enhanced signaling through ligand-independent translocation of the protein to the Golgi, protecting cells from viral infections but preventing their efficient immune priming. Additionally, endothelial cell activation was promoted and further exacerbated by cytokine secretion by SAVI immune cells, resulting in inflammation and endothelial damage. Our findings identify STING F269S mutation as a novel pathogenic variant causing SAVI, highlight the importance of the crosstalk between endothelial and immune cells in the context of lung disease, and contribute to a better understanding of how aberrant STING activation can cause pathology.
Topics: Membrane Proteins; Humans; Endothelial Cells; Lung Diseases, Interstitial; Signal Transduction; Vascular Diseases; Golgi Apparatus; Interferons; Male; Gain of Function Mutation; Mutation; Infant
PubMed: 38953896
DOI: 10.1084/jem.20232167 -
ACS Nano Jul 2024The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus...
The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication. The saOAs could not only efficiently infect tumor cells transferrin receptor-mediated endocytosis but also exhibit enhanced viral replication and tumor oncolysis under ultrasound irradiation. We revealed that the sonosensitizer loaded on the viruses induced the generation of ROS within tumor cells, which triggered JNK-mediated autophagy, ultimately leading to the enhanced viral replication. In mouse models of malignant melanoma, the combination of saOAs and sonodynamic therapy elicited a robust antitumor immune response, resulting in significant inhibition of melanoma growth and improved host survival. This work highlights the potential of sonodynamic therapy in enhancing the effectiveness of OAs and provides a promising platform for fully exploiting the antitumor efficacy of oncolytic virotherapy.
PubMed: 38953884
DOI: 10.1021/acsnano.4c01115 -
Emerging Microbes & Infections Jul 2024SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with...
SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv) form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.
PubMed: 38953857
DOI: 10.1080/22221751.2024.2373307 -
Indian Journal of Public Health Apr 2024
Topics: Humans; Saliva; Nipah Virus; Henipavirus Infections; India
PubMed: 38953831
DOI: 10.4103/ijph.ijph_1185_23 -
Indian Journal of Public Health Apr 2024An outbreak of dengue fever struck Tikarapada village, Rayagada district (April 2020). Among 117 fever cases, 49 tested positive for the dengue NS1 antigen. To identify...
An outbreak of dengue fever struck Tikarapada village, Rayagada district (April 2020). Among 117 fever cases, 49 tested positive for the dengue NS1 antigen. To identify mosquito-related factors in the outbreak, a survey of 101 houses found Aedes breeding sites in 11.6% of containers. Aedes aegypti (79%) and Aedes albopictus (21%) emerged from collected pupae. The village exhibited high (house index = 24.8), (container index = 11.6), (pupal index = 32.7), and (Breteau index = 40.6) indices. The findings confirmed the presence of Aedes and ample breeding sites, suggesting their role in the outbreak. A report recommending integrated vector control measures was submitted to district and state health authorities.
Topics: Dengue; Aedes; Animals; Disease Outbreaks; Humans; India; Mosquito Vectors; Male; Adult; Female; Adolescent; Child; Middle Aged; Dengue Virus; Young Adult; Mosquito Control; Child, Preschool
PubMed: 38953830
DOI: 10.4103/ijph.ijph_749_23 -
Indian Journal of Public Health Apr 2024Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases... (Review)
Review
Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Global Health; Incidence; Prognosis; Prevalence; Tobacco, Smokeless; Papillomaviridae; Human Papillomavirus Viruses
PubMed: 38953816
DOI: 10.4103/ijph.ijph_827_23 -
Indian Journal of Public Health Apr 2024Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India.
BACKGROUND
Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India.
OBJECTIVES
This paper explored the possibility of any ongoing transmission of Zika virus (ZIKV) in the Bhopal region of Central India, where the last outbreak of this disease was reported in 2018.
MATERIALS AND METHODS
We screened a group of 75 febrile patients who had already tested negative for the locally endemic causes of fever like dengue, chikungunya, enteric fever, malaria, and scrub typhus and two groups of asymptomatic healthy individuals represented by blood donors (n = 75) and antenatal mothers (n = 75). We tested blood samples of febrile patients for ZIKV RNA using real-time polymerase chain reaction (PCR), and for the healthy individuals, we determined anti-zika immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay.
RESULTS
ZIKV RNA was not detected in any of the 75 samples tested by real-time PCR assay. Among the voluntary blood donors and antenatal mothers, a total of 10 (15.38%) and 5 (6.66%) individuals were found to be seropositive for anti-ZIKV IgG antibodies, respectively. The seropositive group was found to have higher age 33.06 (±10.83) years as compared to seronegative individuals 26.60 (±5.12) years (P = 0.037).
CONCLUSION
This study, which is the first survey of seroprevalence of anti-Zika antibodies from India, reports an overall seropositivity rate of 10% for anti-Zika antibodies among the healthy population, suggesting an ongoing, low level, silent transmission of ZIKV in the local community.
Topics: Humans; India; Zika Virus Infection; Seroepidemiologic Studies; Adult; Female; Pilot Projects; Male; Zika Virus; Immunoglobulin G; Young Adult; Antibodies, Viral; Middle Aged; RNA, Viral; Adolescent; Enzyme-Linked Immunosorbent Assay; Real-Time Polymerase Chain Reaction
PubMed: 38953800
DOI: 10.4103/ijph.ijph_1098_23 -
Food & Function Jul 2024Obesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes,...
Obesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes, including the development of obesity, and dysbiosis has been observed in obese individuals. In this study, we aimed to evaluate the impact of a new probiotic formulation, containing two probiotic strains and the bioactive compound octacosanol, on body weight, metabolic parameters, and concentrations of certain adipocytokines and appetite-regulating hormones in obese women. This double blind placebo-controlled supplementary intervention study included twenty-five women in the intervention group and twenty-three in the placebo group, and it lasted 12 weeks. Daily oral supplementation included 7 × 10 CFU of 299v (DSM9843), 5 × 10 CFU of var. (DBVPG6763), and 40 mg of octacosanol or placebo. Body weight, metabolic parameters, adipocytokines, and appetite-regulating hormones were assessed before (T0) and after the intervention (T1). After the intervention, significantly lower median concentrations of CRP ( = 0.005) and IL-6 ( = 0.012) were measured in the intervention group than the baseline, while the median concentrations of ghrelin ( = 0.026) and HDL-cholesterol ( = 0.03) were significantly increased. The intervention group had lower CRP levels ( = 0.023) and higher ghrelin levels ( = 0.006) than the placebo group. Significant changes in BMI between groups were not observed. In summary, although the new probiotic formulation showed beneficial effects on IL-6, CRP, HDL, and ghrelin levels, its potential effects on regulating triglyceride, insulin, and glucose levels require further studies before the novel dietary intervention could be considered a useful adjuvant therapy and an effective strategy for the management of obesity and obesity-associated comorbidities.
PubMed: 38953736
DOI: 10.1039/d4fo01269k