bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers in a Cohort of HIV-Infected Patients Single- or Co-Infected with HTLV-1, HTLV-2, and/or HCV: A Cross-Sectional, Observational Study
Authors: Caterino-de-Araujo Adele , Campos Karoline R. , Oliveira Luanda M. S. , Rigato Paula O.
Published: September 2022

HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed such biomarkers in 129 blood samples of HIV-infected individuals matched for age and sex and divided into six groups (G1 (69 HIV); G2 (9 HIV/HTLV-1); G3 (6 HIV/HTLV-2); G4 (11 HIV/HCV); G5 (19 HIV/HCV/HTLV-1); and G6 (15 HIV/HCV/HTLV-2)). Eight cytokines/chemokines from fifteen analytes could be compared. The highest levels of Th1 and pro-inflammatory cytokines were detected in G2 (IFN-γ) and G6 (IL-6 and IL1-β) and of chemokines in G1 (MIG, IP10, RANTES), G4 (MCP1), and G6 (MIP1-β). The highest CD4 cells number and the lowest HIV VL were identified in G3 and the opposite results in G2. Positive correlations between CD4 and CD8 cells counts and IL-6 levels were detected in G2 and G5 and of HIV VL and RANTES in G4. Negative correlations were detected between CD8 and IFN-γ in G4 and HIV VL and RANTES in G6. Despite the small number of the cohort analyzed, and although the cross-sectional study design does not allow firm conclusions, the homogeneity of the characteristics of HIV/HTLV-co-infected individuals regarding age, time and route of HIV acquisition, and criteria for introducing ART enable us to suggest a negative impact of HTLV-1 and a possible protective role of HTLV-2 in HIV infection progression in such patients.
Thermosensitive Hydrogel Wound Dressing Loaded with Bacteriophage Lysin LysP53
Authors: Li Changchang , Nyaruaba Raphael , Zhao Xiaowei , Xue Heng , Li Yuhong , Yang Hang , Wei Hongping
Published: September 2022

Wound infections are prone to attacks from infectious pathogens, including multidrug resistant bacteria that render conventional antimicrobials ineffective. Recently, lysins have been proposed as alternatives to conventional antimicrobials to tackle the menace of multidrug resistance pathogens. The coupling of lysins with a material that will cover the wound may prove beneficial in both protecting and treating wound infections. Hence, in this study, a Gram-negative lysin, LysP53, was coupled with a thermosensitive hydrogel, poloxamer P407, and its efficacy to treat wound infection was tested. In vitro, the addition of LysP53 to the poloxamer did not affect its thermosensitive characteristics, nor did it affect the hydrogel structure. Moreover, the lysin hydrogel could hydrolyze the peptidoglycan, demonstrating that it may have bactericidal activity. Up to 10.4% of LysP53 was released from the hydrogel gradually within 24 h, which led to a 4-log reduction of stationary phase Acinetobacter baumannii. Lastly, the lysin hydrogel was found safe with no cytotoxic effects observed in cells. Ex vivo, LysP53 hydrogel could inhibit bacterial growth on a pig skin decolonization model, with 3-log differences compared to non-treated groups. Overall, our results suggest that lysin-loaded hydrogels may provide a novel solution to treat wound infections caused by resistant bacteria.
A Potential Role for Substance P in West Nile Virus Neuropathogenesis
Authors: Ronca Shannon E. , Gunter Sarah M. , Kairis Rebecca Berry , Lino Allison , Romero Jonathan , Pautler Robia G. , Nimmo Alan , Murray Kristy O.
Published: September 2022

Of individuals who develop West Nile neuroinvasive disease (WNND), ~10% will die and >40% will develop long-term complications. Current treatment recommendations solely focus on supportive care; therefore, we urgently need to identify novel and effective therapeutic options. We observed a correlation between substance P (SP), a key player in neuroinflammation, and its receptor Neurokinin-1 (NK1R). Our study in a wild-type BL6 mouse model found that SP is upregulated in the brain during infection, which correlated with neuroinvasion and damage to the blood–brain barrier. Blocking the SP/NK1R interaction beginning at disease onset modestly improved survival and prolonged time to death in a small pilot study. Although SP is significantly increased in the brain of untreated WNND mice when compared to mock-infected animals, levels of WNV are unchanged, indicating that SP likely does not play a role in viral replication but may mediate the immune response to infection. Additional studies are necessary to define if SP plays a mechanistic role or if it represents other mechanistic pathways.
SARS-CoV-2 Spike and Nucleocapsid Antibody Response in Vaccinated Croatian Healthcare Workers and Infected Hospitalized Patients: A Single Center Cohort Study
Authors: Brlić Paola Kučan , Pavletić Martina , Lerga Mate , Krstanović Fran , Matešić Marina Pribanić , Miklić Karmela , Malić Suzana , Mikša Leonarda , Pajcur Maja , Peruč Dolores , Schubert Maren , Bertoglio Federico , Arapović Jurica , Protić Alen , Šustić Alan , Milošević Marko , Šain Luka Čičin , Jonjić Stipan , Lisnić Vanda Juranić , Brizić Ilija
Published: September 2022

Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees’ anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination.
Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection
Authors: Ferreira da Silva Ana Caroline , Cunha-Silva Marlone , Sevá-Pereira Tiago , Mazo Daniel F.
Published: September 2022

Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.
Phage Diving: An Exploration of the Carcharhinid Shark Epidermal Virome
Authors: Hesse Ryan D. , Roach Michael , Kerr Emma N. , Papudeshi Bhavya , Lima Laís F. O. , Goodman Asha Z. , Hoopes Lisa , Scott Mark , Meyer Lauren , Huveneers Charlie , Dinsdale Elizabeth A.
Published: September 2022

The epidermal microbiome is a critical element of marine organismal immunity, but the epidermal virome of marine organisms remains largely unexplored. The epidermis of sharks represents a unique viromic ecosystem. Sharks secrete a thin layer of mucus which harbors a diverse microbiome, while their hydrodynamic dermal denticles simultaneously repel environmental microbes. Here, we sampled the virome from the epidermis of three shark species in the family Carcharhinidae: the genetically and morphologically similar Carcharhinus obscurus (n = 6) and Carcharhinus galapagensis (n = 10) and the outgroup Galeocerdo cuvier (n = 15). Virome taxonomy was characterized using shotgun metagenomics and compared with a suite of multivariate analyses. All three sharks retain species-specific but highly similar epidermal viromes dominated by uncharacterized bacteriophages which vary slightly in proportional abundance within and among shark species. Intraspecific variation was lower among C. galapagensis than among C. obscurus and G. cuvier. Using both the annotated and unannotated reads, we were able to determine that the Carcharhinus galapagensis viromes were more similar to that of G. cuvier than they were to that of C. obscurus, suggesting that behavioral niche may be a more prominent driver of virome than host phylogeny.
Obesity and Dysmetabolic Factors among Deceased COVID-19 Adults under 65 Years of Age in Italy: A Retrospective Case-Control Study
Authors: Kondili Loreta A. , Quaranta Maria Giovanna , Viganò Mauro , Tata Xhimi , D’Angelo Franca , Lo Noce Cinzia , Palmieri Luigi , Onder Graziano , D’Amico Federico , Inglese Elvira , Puoti Massimo , Aghemo Alessio , Tosti Maria Elena
Published: September 2022

Background: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. Methods: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February–December 2020. Multivariate logistic regression identified the mortality risk factors. Results: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07–14.76), obesity (adjOR 8.58, CI 3.30–22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06–94.22), heart disease (adjOR 17.68, 95% CI 3.80–82.18), cancer (adjOR 13.28, 95% CI 4.25–41.51) and male sex (adjOR 5.24, 95% CI 2.30–11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. Conclusion: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals’ death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.
A Simple and Effective Method to Concentrate Hepatitis C Virus: Aqueous Two-Phase System Allows Highly Efficient Enrichment of Enveloped Viruses
Authors: Kim Heesun , Yi Johan , Yu Jinbae , Park Jaesung , Jang Sung Key
Published: September 2022

To investigate the proliferation cycle of a virus, virus-host interaction, and pathogenesis of a virus, virion particles must be concentrated from the media of virus cell culture or the sera of virus-infected patients. Ultracentrifugation of the culture media is a standard method for concentrating virion particles. However, this method is time-consuming and requires special equipment (ultracentrifuge). Moreover, a large number of infectious viruses are lost during enrichment. We developed a new method of hepatitis C virus (HCV) concentration to overcome the issues associated with traditional methods of virus concentration. We used an aqueous two-phase system (ATPS) to concentrate the virus. HCV, which causes various liver diseases, such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, was used as a model virus to test the efficacy and reliability of the ATPS. The efficiency of HCV concentration by the ATPS was approximately three times higher than that by ultracentrifugation. Moreover, the infectivity of the concentrated HCV, which is a labile virus, remained the same after concentration of the virus by the ATPS. Considering the simplicity and effectiveness of the ATPS, it is the method of choice for concentrating viruses.
SARS-CoV-2 Production, Purification Methods and UV Inactivation for Proteomics and Structural Studies
Authors: Plavec Zlatka , Domanska Aušra , Liu Xiaonan , Laine Pia , Paulin Lars , Varjosalo Markku , Auvinen Petri , Wolf Sharon G. , Anastasina Maria , Butcher Sarah J.
Published: September 2022

Severe acute respiratory syndrome coronavirus-2 is the causative agent of COVID-19. During the pandemic of 2019–2022, at least 500 million have been infected and over 6.3 million people have died from COVID-19. The virus is pleomorphic, and due to its pathogenicity is often handled in very restrictive biosafety containments laboratories. We developed two effective and rapid purification methods followed by UV inactivation that allow easy downstream handling of the virus. We monitored the purification through titering, sequencing, mass spectrometry and electron cryogenic microscopy. Although pelleting through a sucrose cushion, followed by gentle resuspension overnight gave the best particle recovery, infectivity decreased, and the purity was significantly worse than if using the size exclusion resin Capto Core. Capto Core can be used in batch mode, and was seven times faster than the pelleting method, obviating the need for ultracentrifugation in the containment laboratory, but resulting in a dilute virus. UV inactivation was readily optimized to allow handling of the inactivated samples under standard operating conditions. When containment laboratory space is limited, we recommend the use of Capto Core for purification and UV for inactivation as a simple, rapid workflow prior, for instance, to electron cryogenic microscopy or cell activation experiments.
Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018
Authors: Ismael Nalia , Wilkinson Eduan , Mahumane Isabel , Gemusse Hernane , Giandhari Jennifer , Bauhofer Adilson , Vubil Adolfo , Mambo Pirolita , Singh Lavanya , Mabunda Nédio , Bila Dulce , Engelbrecht Susan , Gudo Eduardo , Lessells Richard , de Oliveira Túlio
Published: September 2022

HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time.
Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus
Authors: Mucker Eric M. , Shamblin Josh D. , Goff Arthur J. , Bell Todd M. , Reed Christopher , Twenhafel Nancy A. , Chapman Jennifer , Mattix Marc , Alves Derron , Garry Robert F. , Hensley Lisa E.
Published: September 2022

The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models for evaluating the efficacy of medical countermeasures. Here we addressed one criticism of the model, a requirement for a high-titer administration of virus, as well as improving our understanding of monkeypox virus pathogenesis. To do so, we infected macaques with a challenge dose containing a characterized inoculum enriched for the extracellular form of monkeypox virus. Although there were some differences between diseases caused by the enriched preparation compared with a relatively similar unpurified preparation, we were unable to reduce the viral input with the enriched preparation and maintain severe disease. We found that inherent factors contained within the serum of nonhuman primate blood affect the stability of the monkeypox extracellular virions. As a first step to study a role of the extracellular form in transmission, we also showed the presence of this form in the oropharyngeal swabs from nonhuman primates exposed to monkeypox virus.
Analysis of Adverse Effects of COVID-19 Vaccines Experienced by Healthcare Workers at Guizhou Provincial Staff Hospital, China
Authors: Wei Yunhua , Wang Yan , Liu Lin , Zha Yan , Yang Yuqi , Wang Yuanlin , Roberts Neil , Li Yaying
Published: September 2022

Objective: A retrospective survey was conducted of adverse events following immunization (AEFI) experienced by health care workers (HCWs) in a relatively remote ethnic region in southwest China (Guizhou Province) who received COVID-19 vaccines. Methods: From 18 January 2021 to 21 January 2022, all HCWs of Guizhou Provincial Staff Hospital, China, who received at least one dose of inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), or one dose of adenovirus type-5 (Ad5) vectored COVID-19 vaccine were asked to complete a self-report questionnaire to provide information on any adverse events that may have occurred in the first 3 days after injection. The frequency of AEFI corresponding to the three types of vaccines were compared and the potential risks of AEFI due to the three different vaccines were predicted by multivariate logistic regression analysis. Results: Of the 904 HCWs who completed the survey, the rates of AEFI were 10.1% (80/794) due to Vero cell, 16.3% (13/80) due to CHO cell, and 46.67% (14/30) due to Ad5 vectored vaccines, and the rates were significantly different (χ2 = 38.7, p < 001) between the three vaccines. Multivariate logistic regression models predict that (1) compared to the Ad 5 vectored group, the risk of AEFI occurrence in the Vero cell group was reduced by about 85.9% (OR = 0.141, 95% CI: 0.065–0.306, p < 0.001) and in the CHO cell group by about 72.1% (OR = 0.279, 95% CI: 0.107–0.723, p = 0.009), (2) the odds for women experiencing AEFI were about 2.1 (OR = 2.093, 95% CI: 1.171–3.742, p = 0.013) times as high as those of men, and (3) the risk of AEFI for HCWs with a Bachelor’s degree or above was about 2.2 (OR = 2.237, 95% CI: 1.434–3.489, p = 0.001) times higher than in HCWs who do not have a Bachelor’s degree. Conclusions: 1. The inactivated COVID-19 vaccine (Vero cell), recombinant novel coronavirus vaccine (CHO cell), and adenovirus type-5 (Ad5) vectored COVID-19 vaccine made in China are safe and relatively broad-spectrum. 2. The prevalence of AEFI is more common in women healthcare workers. 3. The risk of AEFI was higher in those with a Bachelor’s degree or above and may be related to the psychological and social effects triggered by the global COVID-19 pandemic.
Examining the Prevailing Negative Sentiments Related to COVID-19 Vaccination: Unsupervised Deep Learning of Twitter Posts over a 16 Month Period
Authors: Ng Qin Xiang , Lim Shu Rong , Yau Chun En , Liew Tau Ming
Published: September 2022

Despite the demonstrated efficacy, safety, and availability of COVID-19 vaccines, efforts in global mass vaccination have been met with widespread scepticism and vaccine hesitancy or refusal. Understanding the reasons for the public’s negative opinions towards COVID-19 vaccination using Twitter may help make new headways in improving vaccine uptake. This study, therefore, examined the prevailing negative sentiments towards COVID-19 vaccination via the analysis of public twitter posts over a 16 month period. Original tweets (in English) from 1 April 2021 to 1 August 2022 were extracted. A bidirectional encoder representations from transformers (BERT)-based model was applied, and only negative sentiments tweets were selected. Topic modelling was used, followed by manual thematic analysis performed iteratively by the study investigators, with independent reviews of the topic labels and themes. A total of 4,448,314 tweets were analysed. The analysis generated six topics and three themes related to the prevailing negative sentiments towards COVID-19 vaccination. The themes could be broadly understood as either emotional reactions to perceived invidious policies or safety and effectiveness concerns related to the COVID-19 vaccines. The themes uncovered in the present infodemiology study fit well into the increasing vaccination model, and they highlight important public conversations to be had and potential avenues for future policy intervention and campaign efforts.
Antibody Response and Adverse Events of AZD1222 COVID-19 Vaccination in Patients Undergoing Dialysis: A Prospective Cohort Study
Authors: Wang Hsi-Hao , Wu Jia-Ling , Chang Min-Yu , Wu Hsin-Mian , Ho Li-Chun , Chi Po-Jui , Wu Ching-Fang , Lee Wan-Chia , Liou Hung-Hsiang , Hung Shih-Yuan , Lee Yi-Che
Published: September 2022

This study observed the antibody response and adverse events of AZD1222 (Oxford/AstraZeneca) vaccination in dialysis patients. A prospective cohort study was conducted in E-Da Healthcare Group hospitals between 1 July and 30 November 2021. Patients receiving hemodialysis (HD, n = 204) or peritoneal dialysis (PD, n = 116) were enrolled alongside healthy subjects (control, n = 34). Anti-SARS-CoV-2 S1 RBD IgG antibodies were measured before the first vaccination (T0), four to six weeks afterwards (T1), one week before the second dose (T2), and four to six weeks afterwards (T3). Adverse events were recorded one week after each dose. The positive IgG rates in the HD (T1: 72%; T2: 62%) and PD (T1: 69%; T2: 70%) groups were lower than the control group (T1: 97%; T2: 91%), with lower median antibody titers. At T3, the positive antibody response rates (HD: 94%; PD: 93%; control: 100%) and titers were similar. Titers were higher after the second dose in all groups. Adverse events were more severe after the first dose and less common with HD than PD or controls. Dialysis patients exhibited lower antibody responses than controls after the first dose of the AZD1222 vaccine but achieved similar responses after consecutive vaccination. Age, health status, two vaccine doses, and alcohol consumption may influence antibody levels.
Oral Vaccination Using a Probiotic Vaccine Platform Combined with Prebiotics Impacts Immune Response and the Microbiome
Authors: Fox Bridget E. , Vilander Allison C. , Gilfillan Darby , Dean Gregg A. , Abdo Zaid
Published: September 2022

Unique to mucosal vaccination is the reciprocal influence of the microbiome and mucosal immune responses, where the immune system is constantly balancing between the clearance of pathogens and the tolerance of self-antigen, food, and the microbiota. Secretory IgA plays a major role in maintaining the homeostasis of a healthy gut microbiome. Natural polyreactive IgA often coats members of the commensal microbiota to aid in their colonization, while high-affinity specific IgA binds to pathogens resulting in their clearance. We developed a probiotic-based mucosal vaccination platform using the bacterium Lactobacillus acidophilus (rLA) with the potential to influence this balance in the IgA coating. In this study, we sought to determine whether repeated administration of rLA alters the host intestinal microbial community due to the immune response against the rLA vaccine. To address this, IgA-seq was employed to characterize shifts in IgA-bound bacterial populations. Additionally, we determined whether using rice bran as a prebiotic would influence the immunogenicity of the vaccine and/or IgA-bound bacterial populations. Our results show that the prebiotic influenced the kinetics of rLA antibody induction and that the rLA platform did not cause lasting disturbances to the microbiome.
Cost-Effectiveness of Intranasal Live-Attenuated Influenza Vaccine for Children: A Systematic Review
Authors: Chan Kenneth , Wong Charlene , Choi Horace
Published: September 2022

Introduction: The public health burden of seasonal influenza is significant, and influenza vaccination is the most effective preventive strategy. Nonetheless, the recommendation of influenza immunization in the pediatric population is still underrepresented. Our work aimed to assess the cost-effectiveness of pediatric influenza vaccination with the intranasal live-attenuated influenza vaccine (LAIV). Methods: We performed a systematic review of publications from PubMed/MEDLINE, Embase, and Scopus, covering the period from 1 January 2000 to 30 April 2022. We searched for economic evaluations that studied the impacts of LAIV among children or the pediatric population. Studies that considered incremental cost-effectiveness ratios (ICERs), in terms of cost per gain in life years, quality adjusted life years, or disability-adjusted life years, were covered. The Consensus Health Economic Criteria (CHEC) Extended Checklist was adopted to check the quality of the included studies. Results: Thirteen studies were included for the final review that were of good or excellent quality. The implementation of influenza vaccination with intranasal LAIV in the pediatric population was cost-effective when compared to the immunization strategies for the elderly and the high-risk groups alone or with no vaccination. The efficacy of LAIV for children, vaccination coverage, and the vaccine price were significant factors to the cost-effectiveness of influenza vaccination for children. Another significant contribution to the cost-effectiveness was the herd immunity arising from pediatric immunization against influenza. Conclusions: The implementation of influenza vaccination in the pediatric population with LAIV is cost-effective. Policymakers and health authorities may consider the evidence on the development of the pediatric influenza vaccination in their immunization schedules.
Correlations between Circulating and Tumor-Infiltrating CD4+ Treg Subsets with Immune Checkpoints in Colorectal Cancer Patients with Early and Advanced Stages
Authors: Al-Mterin Mohammad A. , Murshed Khaled , Elkord Eyad
Published: September 2022

The existence of various T regulatory cell (Treg) subsets in colorectal cancer (CRC) could play a variety of functions in the regulation of anti-cancer immunity. We studied correlations between CD4+ Treg subsets with the expression of immunological checkpoints on CD4+ T cells, including PD-1, TIM-3, LAG-3, and CTLA-4 in CRC patients with early and advanced TNM staging. Strong positive correlations were found between frequencies of FoxP3+ Tregs and FoxP3+Helios+ Tregs with frequencies of various immune checkpoint-expressing CD4+ T cells in the tumor microenvironment (TME). However, there were strong negative correlations between frequencies of FoxP3−Helios− T cells and these immune checkpoint-expressing CD4+ T cells. Specifically, in the TME, we found that the correlations between FoxP3+ Tregs, FoxP3+Helios+ Tregs, FoxP3+Helios− Tregs, and FoxP3−Helios− T cells with CD4+LAG-3+ T cells and CD4+CTLA-4+ T cells were higher in patients with early stages, suggesting the potential of these highly immunosuppressive cells in inhibiting inflammatory responses in the TME. However, the correlations between FoxP3+ Tregs, FoxP3+Helios+ Tregs, and FoxP3−Helios− T cells with CD4+TIM-3+ T cells were higher in patients with advanced stages. This is the first study to explore correlations of Treg subpopulations with immune checkpoint-expressing CD4+ T cells in CRC based on clinicopathological features of CRC patients. The findings of our study provide a justification for focusing on these cells that possess highly immunosuppressive features. Understanding the correlations between different immune checkpoints and Treg subsets in CRC patients has the potential to enhance our understanding of core mechanisms of Treg-mediated immunosuppression in cancer.
An Assessment and Comparison of the Efficacy of Two Licensed Tetravalent Leptospira Vaccines for Dogs Using an Improved Challenge Model
Authors: Klaasen Henricus Leo Bernardus Maria , Veen Mark van der , Dorrestein-Spierenburg Christina Maria , Cao Qi
Published: September 2022

An objective of the present studies was to compare the protective effects of two European licensed canine tetravalent leptospirosis vaccines, Nobivac L4 and Versican Plus L4. Four similar challenge studies in beagle dogs were performed. In each study the dogs were assigned to one of three treatment groups as follows: group 1, Nobivac L4; group 2, Versican Plus L4; group 3, non-vaccinated control group. Two vaccinations were followed by a Leptospira challenge. Strains of the following serogroups were used for challenge: study 1, Grippotyphosa; study 2, Icterohaemorrhagiae; study 3, Canicola; study 4, Australis. Parameters of efficacy were antibody titres; body temperature; clinical signs; cultures of Leptospira bacteria from the blood, urine, kidney and liver; rapid urinalysis; macroscopic and histopathological examination at necropsy. It was concluded that compared to vaccination with Versican Plus L4, vaccination with Nobivac L4 resulted in generally better control of leptospirosis disease parameters after the challenge including a complete prevention of the clinical signs following a Grippotyphosa and Icterohaemorrhagiae challenge. In contrast, vaccination with Versican Plus L4 only prevented infection by Australis and shedding by Grippotyphosa and Australis but it did not lead to any statistically significant reduction of either infection or shedding following an Icterohaemorrhagiae challenge.
Development of an ELISA-Based Potency Assay for Inactivated Influenza Vaccines Using Cross-Reactive Nanobodies
Authors: Cheung Chung Y. , Dubey Sitara , Hadrovic Martina , Ball Christina R. , Ramage Walter , McDonald Jacqueline U. , Harvey Ruth , Hufton Simon E. , Engelhardt Othmar G.
Published: September 2022

Inactivated vaccines are the main influenza vaccines used today; these are usually presented as split (detergent-disrupted) or subunit vaccines, while whole-virus-inactivated influenza vaccines are rare. The single radial immune diffusion (SRD) assay has been used as the gold standard potency assay for inactivated influenza vaccines for decades; however, more recently, various alternative potency assays have been proposed. A new potency test should be able to measure the amount of functional antigen in the vaccine, which in the case of influenza vaccines is the haemagglutinin (HA) protein. Potency tests should also be able to detect the loss of potency caused by changes to the structural and functional integrity of HA. To detect such changes, most alternative potency tests proposed to date use antibodies that react with native HA. Due to the frequent changes in influenza vaccine composition, antibodies may need to be updated in line with changes in vaccine viruses. We have developed two ELISA-based potency assays for group 1 influenza A viruses using cross-reactive nanobodies. The nanobodies detect influenza viruses of subtype H1N1 spanning more than three decades, as well as H5N1 viruses, in ELISA. We found that the new ELISA potency assays are sensitive to the nature of the reference antigen (standard) used to quantify vaccine antigens; using standards matched in their presentation to the vaccine type improved correspondence between the ELISA and SRD assays.
Cutaneous Adverse Reactions to SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis
Authors: Bellinato Francesco , Fratton Zeno , Girolomoni Giampiero , Gisondi Paolo
Published: September 2022

Background: An increasing number of cutaneous adverse reactions (CARs) to SARS-CoV-2 vaccines have been reported, but their incidence is debated. Objective: To estimate the pooled incidence of CARs to SARS-CoV-2 vaccines in the general adult population. Methods: A systematic review and meta-analysis of original articles published on MEDLINE via PubMed and Web Of Science from 1 January 2020 to 18 July 2022 was undertaken. Studies reporting the incidence proportion of CARs (defined as number of new cases of CARs on the total of vaccinated people) were included. All types of SARS-CoV-2 vaccine were included. People receiving at least one dose were considered eligible. Local cutaneous reactions were excluded. Results: A total of 970 records were identified and screened by title and abstract; 22 observational studies were included with aggregate data on 93,165 participants. The pooled incidence of overall CARs was 5% (95%CI 4–6%; I2 = 99%; p < 0.001), ranging from <0.01 to 19.00%. Most CARs were new onset dermatitis including rash, urticaria and vascular lesions; one case of Steven–Johnson syndrome and six cases of erythema multiforme were reported. In the sensitivity analysis we found that the incidence of CARs after the first and second dose was similar, i.e., 3% (95%CI 2–3%; I2 = 96%; p < 0.001) and 3% (95%CI 2–4%; I2 = 97%; p < 0.001), respectively. The magnitude of incidence of CARs remained unchanged independently of vaccine platform and in the general population versus healthcare workers. Conclusions: CARs associated with SARS-CoV-2 vaccines are frequent but mild and self-remitting, whereas severe CARs are rare.
Vaccine Literacy, COVID-19 Vaccine-Related Concerns, and Intention to Recommend COVID-19 Vaccines of Healthcare Workers in a Pediatric and Maternity Hospital: A Cross-Sectional Study
Authors: Maki Wakana , Ishitsuka Kazue , Yamaguchi Koushi , Morisaki Naho
Published: September 2022

Vaccine literacy of healthcare workers (HCWs) may affect the COVID-19 vaccine uptake of the general population. This study aimed to clarify the vaccine literacy level of HCWs in Japan and its impacts on their concerns about vaccines and intention to recommend that others receive vaccines. This cross-sectional survey was conducted in July 2021 based on the recruitment of HCWs in a pediatric and maternity hospital and research center in Tokyo, Japan. All HCWs in this center had the chance to receive the COVID-19 vaccine before the survey, and their vaccine coverage was relatively high, at 95%. A total of 1519 workers answered the questionnaire. The results showed that HCWs with lower functional vaccine literacy had 1.5 times as many concerns about the efficacy of vaccines and 1.6 times as many concerns about the future side effects compared with those with higher literacy. Further, HCWs with higher vaccine literacy were more likely to recommend that older people, people with comorbidities, and pregnant women receive vaccines. Our findings suggest that high vaccine literacy alleviates concerns about COVID-19 vaccines and raised the intention to recommend vaccines to others. To achieve high vaccine coverage, countermeasures such as personalized education are essential.
Mapping the Prevalence of COVID-19 Vaccine Acceptance at the Global and Regional Level: A Systematic Review and Meta-Analysis
Authors: Renzi Erika , Baccolini Valentina , Migliara Giuseppe , Bellotta Ciro , Ceparano Mariateresa , Donia Pierluigi , Marzuillo Carolina , De Vito Corrado , Villari Paolo , Massimi Azzurra
Published: September 2022

Despite the availability of effective and safe vaccines, the acceptance of COVID-19 vaccination is suboptimal. In this meta-analysis we quantified the prevalence estimates of COVID-19 vaccine acceptance with a specific focus on worldwide geographical differences. We searched PubMed, Scopus, Web of Science and PsycInfo up to April 2021 (PROSPERO ID: CRD42021235328). Generalized random-effects linear models with a logit link were used to calculate the pooled estimated rate of vaccine acceptance at both the global and regional level. A meta-regression analysis was performed to assess the association between COVID-19 vaccine acceptance and various characteristics of the studies. Overall, 71 articles yielding 128 prevalence estimates were included. The pooled prevalence of COVID-19 vaccination acceptance rate was 66% (95% CI: 61–71%). This varied by geographic area, ranging from 36% (95% CI: 18–60%) in Africa to 83% (95% CI: 82–84%) in Oceania, and there was high variability between countries (15.4% Cameroon–100% Bhutan). Meta-regression analysis showed that studies that investigated COVID-19 vaccination intentions using multiple choice/scoring gave a vaccine acceptance prevalence lower than studies with only two possible answers (yes/no) (ß: −1.02 95% CI: −1.41 to −0.63). Despite some variation in the estimates, the results showed that one in three people may refuse/delay COVID-19 vaccination.
The Role of Knowledge, Attitude, Confidence, and Sociodemographic Factors in COVID-19 Vaccination Adherence among Adolescents in Indonesia: A Nationwide Survey
Authors: Efendi Defi , Rifani Sabira Ridha , Milanti Ariesta , Efendi Ferry , Wong Cho Lee , Rustina Yeni , Wanda Dessie , Sari Dian , Fabanjo Ivonne Junita , De Fretes Elzina Dina , Mohamad Rini Wahyuni , Sawasemariay Oktoviandi , Faidiban Ruth Harriet , Nur Qoriah , Tiwery Indah Benita , Huda Mega Hasanul , Mobalen Oktovina , Nuraidah
Published: September 2022

COVID-19 vaccination in adolescents is important because the adolescent population has the highest incidence of COVID-19. This study aimed to explore the factors associated with COVID-19 vaccination adherence among Indonesian adolescents. This cross-sectional study involved 7986 adolescents, polled through online and offline surveys conducted in six major islands of Indonesia. The online questionnaire was distributed through popular social messaging and social media platforms. Our team also contacted schools and public places to recruit participants from remote areas. In total, 7299 respondents completed the questionnaire. Binary logistic analysis revealed that higher levels of knowledge, positive attitudes, and confidence in the COVID-19 vaccine were significantly associated with higher COVID-19 vaccination adherence in adolescents. Sociodemographic factors were also significantly associated with higher adherence to vaccination programs. Meanwhile, younger age and habitation in private housing were related to lower adherence to the vaccination program. Parental factors related to adolescent compliance were education level, household income, history of infection of family or friends with COVID-19, and working status. The national authorities and stakeholders should take extensive measures to increase attitude, knowledge, confidence, and family support among adolescence through multiple channels.
Molecular Crosstalk between the Immunological Mechanism of the Tumor Microenvironment and Epithelial–Mesenchymal Transition in Oral Cancer
Authors: Renu Kaviyarasi , Vinayagam Sathishkumar , Veeraraghavan Vishnu Priya , Mukherjee Anirban Goutam , Wanjari Uddesh Ramesh , Prabakaran D. S. , Ganesan Raja , Dey Abhijit , Vellingiri Balachandar , Kandasamy Sabariswaran , Ramanathan Gnanasambandan , Doss C George Priya , George Alex , Gopalakrishnan Abilash Valsala
Published: September 2022

Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer.
Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus
Authors: Vijayanand Sharon , Patil Smital , Joshi Devyani , Menon Ipshita , Braz Gomes Keegan , Kale Akanksha , Bagwe Priyal , Yacoub Shadi , Uddin Mohammad N. , D’Souza Martin J.
Published: September 2022

This ‘proof-of-concept’ study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with adjuvant MP encapsulating Alhydrogel® and AddaVax. We characterized the vaccine MP for size, surface charge, morphology, and encapsulation efficiency. Further, we evaluated the in vitro immunogenicity, cytotoxicity, and antigen-presentation of vaccine/adjuvant MP in murine dendritic cells (DCs). Additionally, we tested the in vivo immunogenicity of the MP vaccine in mice through MN administration. We evaluated the serum IgG, IgA, IgG1, and IgG2a responses using an enzyme-linked immunosorbent assay. The results indicate that the particulate form of the vaccine is more immunogenic than the antigen suspension in vitro. We found the vaccine/adjuvant MP to be non-cytotoxic to DCs. The expression of antigen-presenting molecules, MHC I/II, and their costimulatory molecules, CD80/40, increased with the addition of the adjuvants. Moreover, the results suggest that the MP vaccine is cross presented by the DCs. In vivo, the adjuvanted MP vaccine induced increased antibody levels in mice following vaccination and will further be assessed for its cell-mediated responses.
Role of Immune Cells and Receptors in Cancer Treatment: An Immunotherapeutic Approach
Authors: Mukherjee Anirban Goutam , Wanjari Uddesh Ramesh , Namachivayam Arunraj , Murali Reshma , Prabakaran D. S. , Ganesan Raja , Renu Kaviyarasi , Dey Abhijit , Vellingiri Balachandar , Ramanathan Gnanasambandan , Doss C. George Priya , Gopalakrishnan Abilash Valsala
Published: September 2022

Cancer immunotherapy moderates the immune system’s ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer and the immune system. Immune responses to tumors and lymphoid malignancies are influenced by B cells, γδT cells, NK cells, and dendritic cells (DCs). Cancer immunotherapy, which encompasses adoptive cancer therapy, monoclonal antibodies (mAbs), immune checkpoint therapy, and CART cells, has revolutionized contemporary cancer treatment. This article reviews recent developments in immune cell regulation and cancer immunotherapy. Various options are available to treat many diseases, particularly cancer, due to the progress in various immunotherapies, such as monoclonal antibodies, recombinant proteins, vaccinations (both preventative and curative), cellular immunotherapies, and cytokines.
Vaccines Administration in the Perspective of Patient Safety and Quality of Healthcare: Lesson from the Experience of an Italian Teaching Hospital for Pandemic Preparedness
Authors: De Micco Francesco , De Benedictis Anna , Sommella Lorenzo , Di Mattia Andrea , Campanozzi Laura Leondina , Alloni Rossana , Tambone Vittoradolfo
Published: September 2022

The development and administration of vaccines against COVID-19 was a key element in the fight against the pandemic, as it protected health systems and helped restore global economies. National implementation plans and vaccination strategies for COVID-19 vaccines ensured the immunization of large segments of the population in the shortest time. However, even before the start of the vaccination campaign, it was clear to decision-makers that the usual methods of vaccination were not suitable. The aim of this report is to share the experience of an Italian teaching hospital in the organisation of spaces and activities of healthcare workers to realise a safe vaccination campaign. An in-depth analysis of how the vaccination campaign was organised could be useful to understand strengths and weaknesses learnt from this experience and plan an effective, efficient, and resilient response to future pandemics right away. The adoption of a systemic clinical risk management (SCRM) could guarantee healthcare organizations a more adequate and resilient response in an ethics of a job well done perspective, allowing them to maintain high patient safety standards regardless of the contingent situation for which safety first should be the motto of a disaster response plan.