Human Adenovirus Type Research Articles

Effect of Human Adenovirus Type 35 Concentration on Its Inactivation and Sorption on Titanium Dioxide Nanoparticles.

Removal of pathogenic viruses from water resources is critically important for sanitation and public health. Nanotechnology is a promising technology for virus inactivation. In this paper, the effects of titanium dioxide (TiO2) anatase nanoparticles (NPs) on humanadenovirustype 35 (HAdV-35) removal under static and dynamic (with agitation) batch conditions were comprehensively studied. Batch experiments were performed at room temperature (25°C) with and without ambient light using three different initial virus concentrations. The virus inactivation experimental data were satisfactorily fitted with a pseudo-first-order expression with a time-dependent rate coefficient. The experimental results demonstrated that HAdV-35 sorption onto TiO2 NPs was favored with agitation under both ambient light and dark conditions. However, no distinct relationships between virus initial concentration and removal efficiency could be established from the experimental data.

Detection and quantification of adenovirus, polyomavirus, and papillomavirus in urban sewage.

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 102 to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses.

Genomic Expedition: Deciphering Human Adenovirus Strains from the 2023 Outbreak in West Bengal, India: Insights into Viral Evolution and Molecular Epidemiology.

Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022-2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four randomly selected samples underwent whole-genome sequencing. Analysis revealed a prevalent recombinant strain, merging type 3 and type 7 of human mastadenovirus B1 (HAd-B1) species, indicating the emergence of recent strains of species B in India. Furthermore, distinctions in VA-RNAs and the E3 region suggested that current circulating strains of human mastadenovirus B1 (HAd-B1) possess the capacity to evade host immunity, endure longer within hosts, and cause severe respiratory infections. This study underscores the significance of evaluating the complete genome sequence of HAdV isolates to glean insights into their outbreak potential and the severity of associated illnesses.

Initial safety assessment of the endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer: NRG-GI007.

341 Background: Definitive chemoradiation (CRT) is a standard-of-care for patients (Pts) with medically inoperable esophageal cancer (EC). The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that about half of Pts have locally persistent disease. OBP-301 is a conditionally restricted, replication-competent adenovirus derived from human adenovirus type 5 that adds a human Telomerase Reverse Transcriptase (hTERT) gene promoter, replicating only in tumor cells to cause lysis. It may cause immunogenic cell death, enhance RT, and improve local control. OBP-301 was previously studied with RT in Japanese esophageal cancer Pts and shown to be safe and has promising activity.1 Methods: In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 is added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fractions) for Pts with medically inoperable EC. Pts receive 1-2mL of intratumoral OBP-301 1×1012virus particles/ml via endoscopy 3 days prior to and then at days 12 and 26 of CRT. The primary endpoint is dose-limiting toxicity (DLT), defined as adverse events (AEs, by CTCAE v5) definitely or probably attributed to OBP-301 that meet either of the following: (1) leading to a >14-day cumulative delay in CRT or (2) any grade ≥ 3 AE EXCEPT: grade 3 nausea/vomiting, grade 3 esophagitis or dehydration, first occurrence of grade 3/4 neutropenia, or grade 3/4 lymphopenia. Initially, 6 evaluable Pts (eligible and started protocol treatment) are enrolled. If protocol defined DLT occurs in ≤1 of 6 Pts, the dose will be deemed safe and an expansion cohort of 9 more will be enrolled to further assess safety and obtain a preliminary assessment of clinical complete response. If ≥2 Pts have a DLT then one de-escalated OBP-301 dose will be assessed. Results: From June 2020 to April 2023, 6 evaluable Pts were enrolled. Median age was 73.5 years, all male. Five Pts had adenocarcinoma and 1 had squamous cell carcinoma; 3 Pts had node-positive disease. All Pts received all planned OBP-301 injections, along with 50.4 Gy RT. Four out of 6 Pts received all 5 weekly doses of chemo for > 85% of planned total dose, and 2 got 4 weekly doses for > 70% of planned total dose. No Pt experienced ³7 day treatment delay. The following treatment-related (attributed as definitely, probably, or possibly related to CRT and/or OBP-301) grade 3 AEs were reported across 5 Pts: decreased neutrophil count (3 Pts), decreased lymphocyte count (2 Pts), decreased WBC (2 Pts), and fever and fatigue (1 Pt each). There were 4 Pts with AEs reported as definitely or probably related to OBP-301, all grade ≤2. No DLT occurred. Conclusions: No DLTs in the 6 evaluable Pts were observed and it is concluded that the initial OBP-301 dose level is safe. NRG-GI007 was reopened on August 7, 2023 to the expansion cohort. Full toxicity and treatment data will be presented. 1. Eur J Cancer 2021;153:98. Clinical trial information: NCT04391049 .

Neutralizing monoclonal antibodies protect against human adenovirus type 55 infection in transgenic mice and tree shrews

ABSTRACT Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

Respiratory syncytial virus among hospitalized patients of severe acute respiratory infection in Bhutan: Cross-sectional study.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, particularly in young children. In Bhutan, respiratory disease continues to be among the top 10 diseases of morbidity for several years. This study aimed to estimate the prevalence of RSV among hospitalized patients with severe acute respiratory infection (SARI) in Bhutan. Respiratory specimens were collected from SARI patients of all ages in 2016 and 2018 following influenza surveillance guidelines. Specimens were tested for influenza and RSV, human metapneumovirus, adenovirus, and human parainfluenza virus types 1, 2, and 3 using real-time reverse-transcription polymerase chain reaction assay. Descriptive statistics were used to analyze the result in STATA 16.1. Of the 1339 SARI specimens tested, 34.8% were positive for at least one viral pathogen. RSV was detected in 18.5% of SARI cases, followed by influenza in 13.4% and other respiratory viruses in 3%. The median age of SARI cases was 3 (IQR: 0.8-21 years)years. RSV detection was higher among children aged 0-6 (Adj OR: 3.03; 95% CI: 1.7-5.39) and 7-23 months (Adj OR: 3.01; 95% CI: 1.77-5.12) compared with the children aged 5-15 years. RSV was also associated with breathing difficulty (Adj OR: 1.73; 95% CI: 1.17-2.56) and pre-existing lung disease, including asthma (Adj OR: 2.78; 95% CI: 0.99-7.8). Respiratory viruses were detected in a substantial proportion of SARI hospitalizations in Bhutan.

Epidemiology and molecular detection of human adenovirus and non-polio enterovirus in fecal samples of children with acute gastroenteritis: A five-year surveillance in northern Brazil.

Acute gastroenteritis (AGE) is a common pediatric infection that remains a significant cause of childhood morbidity and mortality worldwide, especially in low-income regions. Thus, the objective of this study was to detect human adenovirus (HAdV) and non-polio enterovirus (NPEV) in fecal samples from the Gastroenteritis Surveillance Network, and to identify circulating strains by nucleotide sequencing. A total of 801 fecal samples were tested using qPCR/RT-qPCR, and 657 (82.0%) were inoculated into HEp-2C and RD cell lines. The HAdV and NPEV positivity rates obtained using qPCR/RT-qPCR were 31.7% (254/801) and 10.5% (84/801), respectively, with 5.4% (43/801) co-detection. Cytopathic effect was observed in 9.6% (63/657) of patients, 2.7% (18/657) associated with HAdV, and 6.2% (41/657) associated with NPEV after testing by ICC-PCR. A comparison of the two methodologies demonstrated an agreement of 93.5% for EVNP and 64.4% for HAdV. These two viruses were detected throughout the study period, with HAdV positivity rates ranging from 41% in Amapá to 18% in Pará. The NEPV varied from 18% in Pará/Rondônia to 3% in Acre. The most affected age group was over 60 months for both HAdV and NPEV. Samples previously positive for rotavirus and norovirus, which did not show a major difference in the presence or absence of diarrhea, fever, and vomiting, were excluded from the clinical analyses of these two viruses. These viruses circulated over five years, with a few months of absence, mainly during the months corresponding to the waves of SARS-CoV-2 infection in Brazil. Five HAdV species were identified (A, B, C, D, and F), with a greater predominance of HAdV-F41 (56.5%) followed by HAdV-C (15.2%). Three NPEV species (A, B, and C) were detected, with serotypes E14 (19.3%) and CVA-24 (16.1%) being the most prevalent. The present study revealed a high diversity of NPEV and HAdV types circulating in children with AGE symptoms in the northern region of Brazil.

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within E1 or E3 genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both in vitro and in vivo and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs)- follicular helper T (Tfh) cells- germinal centre (GC) / memory B cells (MBCs)- long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the E1 and E3 genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.

Seroprevalence of human adenovirus type 5 neutralizing antibodies in the Philippines.

Human adenovirus (HAdV), particularly the HAdV type 5 (HAdV-5), has been extensively utilized in the development of vector vaccines due to its high immunogenicity, good safety profile, and ease of propagation. However, one of the main challenges in its use is the presence of pre-existing immunity among vaccine recipients. Pre-existing neutralizing antibodies (NAbs) can prevent the uptake of HAdV-5 vectors and reduce vaccine efficacy. Hence, this study investigated the seroprevalence of NAbs against HAdV-5 in urban and rural regions of the Philippines. Luciferase-based neutralization assay was performed on 391 plasma/serum samples. Out of these samples, 346 or 88.5% were positive for HAdV-5 NAbs, and the majority of them (56.8%) had high titers against the virus. Among the regions included in this study, Bicol (Region V) had the highest seroprevalence rate (94.1%). Our findings show that a significant number of adults in the Philippines have pre-existing immunity against HAdV-5. This supports the recommendation that vaccination programs in the country should consider implementing vaccination techniques, such as a prime-boost regimen or addition of booster doses, to address the potential negative effects of pre-existing HAdV-5 immunity in the efficacy of adenoviral vector-based vaccines.

Higher affinities of fibers with cell receptors increase the infection capacity and virulence of human adenovirus type 7 and type 55 compared to type 3.

HAdV-3, -7, and -55 are the predominant types causing acute respiratory disease outbreaks and can lead to severe and fatal pneumonia in children and adults. In recent years, emerging or re-emerging strains of HAdV-7 and HAdV-55 have caused multiple outbreaks globally in both civilian and military populations, drawing increased attention. Clinical studies have reported that HAdV-7 and HAdV-55 cause more severe pneumonia than HAdV-3. This study aimed to investigate the mechanisms explaining the higher severity of HAdV-7 and HAdV-55 infection compared to HAdV-3 infection. Our findings provided evidence linking the receptor-binding protein fiber to stronger infectivity of the strains mentioned above by comparing several fiber-chimeric or fiber-replaced adenoviruses. Our study improves our understanding of adenovirus infection and highlights potential implications, including in novel vector and vaccine development.

Immunogenicity and protective efficacy of a recombinant adenovirus containing the fusion protein of bovine parainfluenza virus type 3 genotype C in mice

Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen of cattle that causes substantial economic losses. A replicating-defective recombinant human adenovirus type 5 (HAd5), carrying a fusion protein of BPIV3 genotype C (HAd5-F), was constructed and evaluated for its immunogenicity and protective efficacy in mice. After intramuscular injection with the HAd5-F, the IgG titers against F proteins increased to 1:102,400, and virus-neutralizing titers increased to 1:256, significantly higher than those in the group injected with inactivated BPIV3C in mice (p<0.05). The splenic CD4+/CD8+T lymphocytes and IFN-γ+/IL-4+ cytokine percentages were more significant in the HAd5-F group than those in the control group. A BPIV3C challenge in a mouse model was used to assess protective efficacy of the HAd5-F. The viral loads in the lungs and tracheas of mice immunized with the HAd5-F were significantly lower than those in the control group (p<0.0001). There were no significant histopathological alterations in the lungs of mice vaccinated with the HAd5-F. These findings suggested that the HAd5-F elicited excellent immunity against BPIV3C infection.

NGR-bearing human adenovirus type 5 infects cells in flotillin- or caveolin-mediated manner depending on the NGR insertion site

Human adenoviruses represent attractive candidates for the design of cancer gene therapy vectors. Modification of adenovirus tropism by incorporating a targeting ligand into the adenovirus capsid proteins allows retargeting of adenovirus towards the cells of interest. Human adenovirus type 5 (HAdV-C5) bearing NGR containing peptide (CNGRCVSGCAGRC) inserted into the fiber (AdFNGR) or the hexon (AdHNGR) protein demonstrated an increased transduction of endothelial cells showing expression of aminopeptidase N, also known as CD13, and αvβ3 integrin both present on tumor vasculature, indicating that NGR-bearing adenoviruses could be used as tools for anti-angiogenic cancer therapy. Here we investigated how AdFNGR and AdHNGR infect cells lacking HAdV-C5 primary receptor, coxsackie and adenovirus receptor, and we showed that both AFNGR and AdHNGR enter cells by dynamin- and lipid raft-mediated endocytosis, while clathrin is not required for endocytosis of these viruses. We present evidence that productive infection of both AdFNGR and AdHNGR involves lipid rafts, with usage of flotillin-mediated cell entry for AdFNGR and limited role of caveolin in AdHNGR transduction efficiency. Lipid rafts play important role in angiogenesis and process of metastasis. Therefore, the ability of AdFNGR and AdHNGR to use lipid raft-dependent endocytosis, involving respectively flotillin- or caveolin-mediated pathway, could give them an advantage in targeting tumor cells lacking HAdV-C5 primary receptor.

Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy.

Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates (P=0.044), whereas the same was not evident in high MSI (MSI-H) versus non-MSI-H patients (P=0.528). We observed a few high-frequency mutation genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) that probably carry functional importance in response to H101 treatment, among which KMT2D and ADAP1 mutations were associated with inferior progression-free survival (PFS) and/or overall survival (OS) (P<0.05). Notably, H101 treatment-induced accumulating subclones or clusters in primary tumors and some (Signature 2) were associated with shorter PFS. We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.

Characterization of Pre-Existing Neutralizing Antibody to Human Adenovirus Types 5 and 49 and Simian Type 23 in Chinese Population.

Recombinant adenovirus vector has been widely used in vaccine development. Due to the pre-existing immunity of human adenovirus type 5 (HAd5) in humans, a range of rare human and chimpanzee adenovirus vectors have been developed. In the previous study, we constructed novel adenovirus vector Sad23L and Ad49L based on simian adenovirus type 23 (SAd23) and human adenovirus type 49 (HAd49), which were used in the development of ZIKV and COVID-19 vaccines. However, the levels of pre-existing neutralizing antibody (NAb) of HAd49 and SAd23 remain unclear in China. In this study, we measured NAbs titers of HAd5, HAd49, and SAd23 in 600 healthy blood donors from 6 regions across China. NAb titer of HAd49 or SAd23 was significantly lower than that of HAd5 (p < 0.001). There was no significant difference in seroprevalence and NAb titers of three adenoviruses between male and female donors. The seropositive rates of HAd5 and SAd23 increased with age growth in a positive correlation (p < 0.01), while in contrast to HAd5, HAd49, and SAd23 had a low level of pre-existing immunity in Chinese population, which suggested that Ad49L and Sad23L vectors could be used in vaccine development for humans.

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies.ClinicalTrials.gov Identifier: NCT05110911.

Molecular epidemiology of circulating human adenoviruses among acute respiratory infection patients seeking healthcare facilities in West Bengal, India

Human adenovirus (HAdV) causes acute respiratory infections leading to mortality in children. This study analyzes the circulating respiratory HAdV genotypes in West Bengal, India during 2018-2022 among symptomatic patients. The overall positivity rate was 6.8%, out of which 26.4% were co-infected with other respiratory viruses. Children aged 2 to 5 years were mostly infected. Phylogenetic analysis revealed that the recombinant HAdV-B type 7/3, which has remarkable outbreak potential, predominantly circulated in this region followed by the non-recombinant HAdV-B type 3/3. Moreover, the amino acid sequences encoded by both the hexon and fiber genes of these two circulating strains possessed a few mutations that mostly diverged from the prototype strain, although the divergence was less pronounced in case of the amino acids encoded by the fiber gene of HAdV-B type 3/3. Overall, the results underscore the need for continuous surveillance of respiratory HAdV types to combat future possible epidemics.

Comparative analysis of the impact of 40 adenovirus types on dendritic cell activation and CD8+ T cell proliferation capacity for the identification of favorable immunization vector candidates.

For the development of new adenovirus (AdV)-based vectors, it is important to understand differences in immunogenicity. In a side-by-side in vitro analysis, we evaluated the effect of 40 AdV types covering human AdV (HAdV) species A through G on the expression of 11 activation markers and the secretion of 12 cytokines by AdV-transduced dendritic cells, and the effect on CD8+ T cell proliferation capacity. We found that the expression of activation markers and cytokines differed widely between the different HAdV types, and many types were able to significantly impair the proliferation capacity of CD8+ T cells. Univariate and multivariate regression analyses suggested an important role of type I interferons in mediating this suppression of CD8+ T cells, which we confirmed experimentally in a proliferation assay using a type I interferon receptor blocking antibody. Using Bayesian statistics, we calculated a prediction model that suggests HAdV types HAdV-C1, -D8, -B7, -F41, -D33, -C2, -A31, -B3 and -D65 as the most favorable candidates for vaccine vector development.

Selenadiazole Inhibited Adenovirus-Induced Apoptosis through the Oxidative-Damage-Mediated Bcl-2/Stat 3/NF-κB Signaling Pathway.

Human adenovirus type 7 (HAdV7) infection causes severe pneumonia, yet there are still no breakthroughs in treatment options for adenovirus, and the road to antiviral drug development faces major challenges. We attempted to find new drugs and we stumbled upon one: selenadiazole. Selenadiazole has been shown to have significant anti-tumor effects due to its unique chemical structure and drug activity. However, its effectiveness against viruses has not been evaluated yet. In our study, selenadiazole also showed superior antiviral activity. In vitro experiments, selenadiazole was able to inhibit adenovirus-mediated mitochondrial-oxidative-damage-related apoptosis, and in in vivo experiments, selenadiazole was able to inhibit apoptosis by modulating the apoptotic signaling pathway Bcl-2/Stat3/NF-κB, etc., and was able to largely attenuate adenovirus-infection-induced pneumonia and lung injury in mice. This study aims to describe a new antiviral treatment option from the perspective of anti-adenovirus-mediated oxidative stress and its associated apoptosis and to provide theoretical guidance for the treatment of clinical adenovirus infection to a certain extent.

The Virucidal Effect of the Chlorination of Water at the Initial Phase of Disinfection May Be Underestimated If Contact Time Calculations Are Used.

For the microbiological safety of drinking water, disinfection methods are used to remove or inactivate microorganisms. Chlorine and chlorine dioxide are often used as disinfectants in drinking water treatment plants (DWTPs). We investigated the effectiveness of these chemicals in inactivate echovirus 30 (E30), simian 11 rotavirus (RV SA11), and human adenovirus type 2 (HAdV2) in purified water from a DWTP. Within two minutes of contact, chlorine dioxide inactivated E30 by 4-log10, RV SA11 by 3-log10, and HAdV2 could not be detected, while chlorine reduced E30 by 3-log10, RV SA11 by 2-3log10, and HAdV2 by 3-4log10. However, viral genomes could be detected for up to 2 h using qPCR. The CT method, based on a combination of disinfectant concentration and contact time, during such a short initial phase, is problematic. The high concentrations of disinfectant needed to neutralize organic matter may have a strong immediate effect on virus viability. This may lead to the underestimation of disinfection and overdosing of disinfectants in water with organic contamination. These results are useful for the selection of disinfection systems for reuse of treated wastewater and in the risk assessment of water treatment processes using chlorine and chlorine dioxide.

An easy pill to swallow: oral recombinant vaccines for the 21st century.

Oral vaccines have a distinctive advantage of stimulating immune responses in the mucosa, where numerous pathogens gain entry and cause disease. Although various efforts have been attempted to create recombinant mucosal vaccines that provoke strong immunogenicity, the outcomes in clinical trials have been weak or inconsistent. Therefore, next-generation mucosal vaccines are needed that are more immunogenic. Here, we discuss oral vaccines with an emphasis on a next-generation mucosal vaccine that utilizes a nonreplicating human recombinant adenovirus type-5 (rAd5) vector. Numerous positive clinical results investigating oral rAd5 vaccines are reviewed, with a summary of the immunogenicity and efficacy results for specific vaccine indications of influenza, norovirus, and SARS-CoV-2. The determination of correlates of protection for oral vaccination and the potential impact this novel vaccine formulation may have on disease transmission are also discussed. In summary, successful oral vaccination can be accomplished and would have major public health benefits if approved.