bluuebunny/crossref_metadata_2025 huggingface dataset:
A Large Cohort Study of SARS-CoV-2 Detection in Saliva: A Non-Invasive Alternative Diagnostic Test for Patients with Bleeding Disorders
Authors: Lopes Josiane Iole França , da Costa Silva Carlos Alexandre , Cunha Rodrigo Guimarães , Soares Alexandra Martins , Lopes Maria Esther Duarte , da Conceição Neto Orlando Carlos , Alves Arthur Daniel Rocha , da Costa Nunes Pimentel Coelho Wagner Luis , Amorim Filho Luiz , Amado Leon Luciane Almeida
Published: December 2021

Diagnosis of SARS-CoV-2 infections is mostly based on the nasopharyngeal swabs (NPS). However, this collection is invasive and uncomfortable, especially for children and patients with coagulopathies, whose NPS collection often causes bleeding. Thus, the aim of this study was to evaluate the usefulness and accuracy of saliva for the diagnosis of COVID-19 in patients presenting bleeding disorders. Samples of NPS, oropharyngeal swabs (OPS), and saliva were collected simultaneously from 1159 hospitalized patients with hematological diseases and from 524 healthcare workers, both symptomatic and asymptomatic for SARS-CoV-2. All samples were evaluated for SARS-CoV-2 by qRT-PCR. SARS-CoV-2 was detected in NPS, OPS and saliva from 16.9%, 14.4% and 15.6% individuals, respectively. Tests in saliva showed sensitivity, specificity, and overall agreement of 73.3%, 96.9% and 92.7% (=0.74), respectively. Salivary tests had good accuracy (AUC = 0.7) for discriminating negative and positive qRT-PCR for SARS-CoV-2. Higher sensitivity was observed in symptomatic than in non-symptomatic patients, as well as in healthy subjects than in patients with hematological disease, in both OPS and saliva. The mean viral load in NPS was significantly higher than in OPS and in saliva samples (p < 0.001). Saliva is a good diagnostic tool to detect SARS-CoV-2, especially among patients symptomatic for COVID-19, and is a valuable specimen for mass screening of hospitalized patients with hematological diseases, especially for those that with bleeding disorders.
Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood–Brain Barrier System
Authors: Fikatas Antonios , Dehairs Jonas , Noppen Sam , Doijen Jordi , Vanderhoydonc Frank , Meyen Eef , Swinnen Johannes V. , Pannecouque Christophe , Schols Dominique
Published: December 2021

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood–brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.
Innate Immune Signaling and Role of Glial Cells in Herpes Simplex Virus- and Rabies Virus-Induced Encephalitis
Authors: Feige Lena , Zaeck Luca M. , Sehl-Ewert Julia , Finke Stefan , Bourhy Hervé
Published: December 2021

The environment of the central nervous system (CNS) represents a double-edged sword in the context of viral infections. On the one hand, the infectious route for viral pathogens is restricted via neuroprotective barriers; on the other hand, viruses benefit from the immunologically quiescent neural environment after CNS entry. Both the herpes simplex virus (HSV) and the rabies virus (RABV) bypass the neuroprotective blood–brain barrier (BBB) and successfully enter the CNS parenchyma via nerve endings. Despite the differences in the molecular nature of both viruses, each virus uses retrograde transport along peripheral nerves to reach the human CNS. Once inside the CNS parenchyma, HSV infection results in severe acute inflammation, necrosis, and hemorrhaging, while RABV preserves the intact neuronal network by inhibiting apoptosis and limiting inflammation. During RABV neuroinvasion, surveilling glial cells fail to generate a sufficient type I interferon (IFN) response, enabling RABV to replicate undetected, ultimately leading to its fatal outcome. To date, we do not fully understand the molecular mechanisms underlying the activation or suppression of the host inflammatory responses of surveilling glial cells, which present important pathways shaping viral pathogenesis and clinical outcome in viral encephalitis. Here, we compare the innate immune responses of glial cells in RABV- and HSV-infected CNS, highlighting different viral strategies of neuroprotection or Neuroinflamm. in the context of viral encephalitis.
Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes
Authors: Schleiss Mark R. , Fernández-Alarcón Claudia , Hernandez-Alvarado Nelmary , Wang Jian Ben , Geballe Adam P. , McVoy Michael A.
Published: December 2021

The development of a vaccine against congenital human cytomegalovirus (HCMV) infection is a major priority. The pentameric complex (PC) of virion envelope proteins gH, gL, UL128, UL130, and UL131A is a key vaccine target. To determine the importance of immunity to the homologous PC encoded by guinea pig cytomegalovirus (GPCMV) in preventing congenital CMV, PC-intact and PC-deficient live-attenuated vaccines were generated and directly compared for immunogenicity and efficacy against vertical transmission in a vertical transmission model. A virulent PC-intact GPCMV (PC/intact) was modified by galK mutagenesis either to abrogate PC expression (PC/null; containing a frame-shift mutation in GP129, homolog of UL128) or to delete genes encoding three MHC Class I homologs and a protein kinase R (PKR) evasin while retaining the PC (3DX/Δ145). Attenuated vaccines were compared to sham immunization in a two-dose preconception subcutaneous inoculation regimen in GPCMV seronegative Hartley guinea pigs. Vaccines induced transient, low-grade viremia in 5/12 PC/intact-, 2/12 PC/null-, and 1/11 3DX/Δ145-vaccinated animals. Upon completion of the two-dose vaccine series, ELISA titers for the PC/intact group (geometic mean titer (GMT) 13,669) were not significantly different from PC/null (GMT 8127) but were significantly higher than for the 3DX/Δ145 group (GMT 6185; p < 0.01). Dams were challenged with salivary gland-adapted GPCMV in the second trimester. All vaccines conferred protection against maternal viremia. Newborn weights were significantly lower in sham-immunized controls (84.5 ± 2.4 g) compared to PC/intact (96 ± 2.3 g), PC/null (97.6 ± 1.9 g), or 3DX/Δ145 (93 ± 1.7) pups (p < 0.01). Pup mortality in sham-immunized controls was 29/40 (73%) and decreased to 1/44 (2.3%), 2/46 (4.3%), or 4/40 (10%) in PC/intact, PC/null, or 3DX/Δ145 groups, respectively (all p < 0.001 compared to control). Congenital GPCMV transmission occurred in 5/44 (11%), 16/46 (35%), or 29/38 (76%) of pups in PC/intact, PC/null, or 3DX/Δ145 groups, versus 36/40 (90%) in controls. For infected pups, viral loads were lower in pups born to vaccinated dams compared to controls. Sequence analysis demonstrated that infected pups in the vaccine groups had salivary gland-adapted GPCMV and not vaccine strain-specific sequences, indicating that congenital transmission was due to the challenge virus and not vaccine virus. We conclude that inclusion of the PC in a live, attenuated preconception vaccine improves immunogenicity and reduces vertical transmission, but PC-null vaccines are equal to PC-intact vaccines in reducing maternal viremia and protecting against GPCMV-related pup mortality.
Possible Arbovirus Found in Virome of Melophagus ovinus
Authors: Litov Alexander G. , Belova Oxana A. , Kholodilov Ivan S. , Gadzhikurbanov Magomed N. , Gmyl Larissa V. , Oorzhak Natalia D. , Saryglar Anna A. , Ishmukhametov Aydar A. , Karganova Galina G.
Published: December 2021

Members of the Lipopteninae subfamily are blood-sucking ectoparasites of mammals. The sheep ked (Melophagus ovinus) is a widely distributed ectoparasite of sheep. It can be found in most sheep-rearing areas and can cause skin irritation, restlessness, anemia, weight loss and skin injuries. Various bacteria and some viruses have been detected in M. ovinus; however, the virome of this ked has never been studied using modern approaches. Here, we study the virome of M. ovinus collected in the Republic of Tuva, Russia. In our research, we were able to assemble full genomes for five novel viruses, related to the Rhabdoviridae (Sigmavirus), Iflaviridae, Reoviridae and Solemoviridae families. Four viruses were found in all five of the studied pools, while one virus was found in two pools. Phylogenetically, all of the novel viruses clustered together with various recently described arthropod viruses. All the discovered viruses were tested on their ability to replicate in the mammalian porcine embryo kidney (PEK) cell line. Aksy-Durug Melophagus sigmavirus RNA was detected in the PEK cell line cultural supernate after the first, second and third passages. Such data imply that this virus might be able to replicate in mammalian cells, and thus, can be considered as a possible arbovirus.
Serum Neutralization Profiles of Straw-Colored Fruit Bats (Eidolon helvum) in Makurdi (Nigeria), against Four Lineages of Lagos Bat Lyssavirus
Authors: Ameh Veronica Odinya , Wu Guanghui , Goharriz Hooman , Shipley Rebecca , Fooks Anthony R. , Sabeta Claude T. , McElhinney Lorraine M.
Published: December 2021

Lagos bat lyssavirus (LBV) comprising four lineages (A, B, C and D) can potentially cause the fatal disease rabies. Although LBV-B was initially isolated in Nigeria in 1956, there is no information on LBV lineages circulating in Nigeria. This study was undertaken for the first time to measure the neutralizing antibodies against four lineages of LBVs in straw-colored fruit bats (Eidolon helvum) in Makurdi, Nigeria. Serum samples (n = 180) collected during two periods (November 2017–March 2018 and November 2018–March 2019) from terminally bled bats captured for human consumption were tested using a modified fluorescent antibody virus neutralization (mFAVN) assay. A high proportion of bat sera (74%) neutralized at least one lineage of LBV (with reciprocal titers from 9 to >420.89) and most of them neutralized LBV-A (63%), followed by LBV-D (49%), LBV-C (45%) and LBV-B (24%). The majority of positive sera (75%, n = 100) neutralized multiple LBV lineages while the remaining 25% (n = 33) neutralized only a single lineage, i.e., LBV-A (n = 23), LBV-D (n = 8) and LBV-C (n = 2). None exclusively neutralized LBV-B. The results suggest that exposure to LBV is common in E. helvum and that LBV-A (but not LBV-B) is likely to be circulating in this region of Nigeria.
JAK-STAT Pathway: A Novel Target to Tackle Viral Infections
Authors: Ezeonwumelu Ifeanyi Jude , Garcia-Vidal Edurne , Ballana Ester
Published: December 2021

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections.
Changes of Host Immunity Mediated by IFN-γ+ CD8+ T Cells in Children with Adenovirus Pneumonia in Different Severity of Illness
Authors: Zheng Ruilin , Li Yinghua , Chen Danyang , Su Jingyao , Han Ning , Chen Haitian , Ning Zhihui , Xiao Misi , Zhao Mingqi , Zhu Bing
Published: December 2021

The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L compared with the healthy control (3.92 × 109/L) and the mild patients (4.27 × 109/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8+ T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8+ T and CD4+ T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ+ CD8+ T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.
Systemic and Intestinal Viral Reservoirs in CD4+ T Cell Subsets in Primary SIV Infection
Authors: Wang Xiaolei , Ziani Widade , Veazey Ronald S. , Xu Huanbin
Published: December 2021

The HIV reservoir size in target CD4+ T cells during primary infection remains unknown. Here, we sorted peripheral and intestinal CD4+ T cells and quantified the levels of cell-associated SIV RNA and DNA in rhesus macaques within days of SIVmac251 inoculation. As a major target cell of HIV/SIV, CD4+ T cells in both tissues contained a large amount of SIV RNA and DNA at day 8–13 post-SIV infection, in which productive SIV RNA highly correlated with the levels of cell-associated SIV DNA. Memory CD4+ T cells had much higher viral RNA and DNA than naïve subsets, yet memory CD4+ T cells co-expressing CCR5 had no significant reservoir size compared with those that were CCR5-negative in blood and intestine. Collectively, memory CD4+ T cells appear to be the major targets for primary infection, and viral reservoirs are equally distributed in systemic and lymphoid compartments in acutely SIV-infected macaques.
Oral Selective TLR8 Agonist Selgantolimod Induces Multiple Immune Cell Responses in Humans
Authors: Ayithan Natarajan , Ghosh Alip , Dwivedi Ankit , Wallin Jeffrey J. , Tan Susanna K. , Chen Diana , Kottilil Shyam , Poonia Bhawna
Published: December 2021

TLR8 agonists have the potential for use as immunomodulatory components in therapeutic modalities for viral infections such as chronic HBV (CHB) and HIV. In this study, using peripheral blood samples from a phase 1a clinical trial, we examined the acute effects of a single oral administration of a selective TLR8 agonist on immune cell phenotypes. Administration of the TLR8 agonist selgantolimod (SLGN) in healthy individuals resulted in alteration in frequencies of peripheral blood monocytes, pDCs, mDCs and MAIT cells. Frequencies of mDCs and lymphoid cells significantly reduced after 8 h of SLGN administration, whereas pDC frequencies significantly increased, with changes possibly reflecting migration of different cell types between peripheral and tissue compartments in response to the agonist. Myeloid cell activation was evident by an upregulated expression of co-stimulatory molecules CD40 and CD86 accompanied by the production of IL-6 and IL-18 from these cells. Concomitantly, there was induction of the early activation marker CD69 on innate and adaptive lymphoid cells, including MAIT and NK cell subsets. Further, these activated lymphoid cells had enhanced expression of the effector molecules granzyme B and perforin. Microarray analysis of isolated lymphocytes and monocytes from baseline and post-SLGN treatment revealed changes in expression of genes involved in cellular response to cytokine stimulus, innate immune response, myeloid cell differentiation and antigen receptor-mediated signaling pathway. In a preliminary analysis of samples from CHB patients treated with selgantolimod, activation of innate and adaptive lymphocytes was evident. In conclusion, this first in-human study shows that selgantolimod administration in humans results in activation of multiple immune cell responses with antiviral potential.
Development of a Novel Double Antibody Sandwich ELISA for Quantitative Detection of Porcine Deltacoronavirus Antigen
Authors: Wang Wei , Li Jizong , Fan Baochao , Zhang Xuehan , Guo Rongli , Zhao Yongxiang , Zhou Junming , Zhou Jinzhu , Sun Dongbo , Li Bin
Published: December 2021

Porcine deltacoronavirus (PDCoV) can cause diarrhea and dehydration in newborn piglets. Here, we developed a double antibody sandwich quantitative enzyme-linked immunosorbent assay (DAS-ELISA) for detection of PDCoV by using a specific monoclonal antibody against the PDCoV N protein and an anti-PDCoV rabbit polyclonal antibody. Using DAS-ELISA, the detection limit of recombinant PDCoV N protein and virus titer were approximately 0.5 ng/mL and 103.0 TCID50/mL, respectively. A total of 59 intestinal and 205 fecal samples were screened for the presence of PDCoV by using DAS-ELISA and reverse transcriptase real-time PCR (RT-qPCR). The coincidence rate of the DAS-ELISA and RT-qPCR was 89.8%. DAS-ELISA had a sensitivity of 80.8% and specificity of 95.6%. More importantly, the DAS-ELISA could detect the antigen of PDCoV inactivated virus, and the viral antigen concentrations remained unchanged in the inactivated virus. These results suggest that DAS-ELISA could be used for antigen detection of clinical samples and inactivated vaccines. It is a novel method for detecting PDCoV infections and evaluating the PDCoV vaccine.
Deciphering the Molecular Basis for Attenuation of Flavobacterium columnare Strain Fc1723 Used as Modified Live Vaccine against Columnaris Disease
Authors: Cai Wenlong , Arias Covadonga R.
Published: December 2021

Vaccines are widely employed in aquaculture to prevent bacterial infections, but their use by the U.S. catfish industry is very limited. One of the main diseases affecting catfish aquaculture is columnaris disease, caused by the bacterial pathogen Flavobacterium columnare. In 2011, a modified-live vaccine against columnaris disease was developed by selecting mutants that were resistant to rifampin. The previous study has suggested that this vaccine is stable, safe, and effective, but the mechanisms that resulted in attenuation remained uncharacterized. To understand the molecular basis for attenuation, a comparative genomic analysis was conducted to identify specific point mutations. The PacBio RS long-read sequencing platform was used to obtain draft genomes of the mutant attenuated strain (Fc1723) and the parent virulent strain (FcB27). Sequence-based genome comparison identified 16 single nucleotide polymorphisms (SNP) unique to the mutant. Genes that contained mutations were involved in rifampin resistance, gliding motility, DNA transcription, toxin secretion, and extracellular protease synthesis. The results also found that the vaccine strain formed biofilm at a significantly lower rate than the parent strain. These observations suggested that the rifampin-resistant phenotype and the associated attenuation of the vaccine strain result from the altered activity of RNA polymerase (RpoB) and possible disrupted protein secretion systems.
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β
Authors: Gao Qi , Yang Yunlong , Quan Weipeng , Zheng Jiachen , Luo Yizhuo , Wang Heng , Chen Xiongnan , Huang Zhao , Chen Xiaojun , Xu Runda , Zhang Guihong , Gong Lang
Published: December 2021

African swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and vaccine development. CD2v and MGF360-505R genes have been implicated in the modulation of the immune response. The molecular mechanisms contributing to innate immunity are poorly understood. In this study, we discover the cytopathic effect and apoptosis of ΔCD2v/ΔMGF360-505R-ASFV after infection in porcine alveolar macrophages (PAMs) was significantly less than wild-type ASFV. We demonstrated that CD2v- and MGF360-505R-deficient ASFV decrease the level of apoptosis by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription. Compared with wild-type ASFV infection, the levels of phospho-NF-κB p65 and p-IκB protein decreased in CD2v- and MGF360-505R-deficient ASFV. Moreover, CD2v- and MGF360-505R-deficient ASFV induced less IL-1β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. We further found that MGF360-12L, MGF360-13L, and MGF-505-2R suppress the promoter activity of NF-κB by reporter assays, and CD2v activates the NF-κB signaling pathway. These findings suggested that CD2v- and MGF360-505R-deficient ASFV could reduce the level of ASFV p30 and the apoptosis of PAMs by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription, which might reveal a novel strategy for ASFV to maintain the replication of the virus in the host.
Overview of Neutralizing Antibodies and Their Potential in COVID-19
Authors: Morales-Núñez José Javier , Muñoz-Valle José Francisco , Torres-Hernández Paola Carolina , Hernández-Bello Jorge
Published: December 2021

The antibody response to respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major focus of COVID-19 research due to its clinical relevance and importance in vaccine and therapeutic development. Neutralizing antibody (NAb) evaluations are useful for the determination of individual or herd immunity against SARS-CoV-2, vaccine efficacy, and humoral protective response longevity, as well as supporting donor selection criteria for convalescent plasma therapy. In the current manuscript, we review the essential concepts of NAbs, examining their concept, mechanisms of action, production, and the techniques used for their detection; as well as presenting an overview of the clinical use of antibodies in COVID-19.
Data-Driven Decision Making and Proactive Citizen–Scientist Communication: A Cross-Sectional Study on COVID-19 Vaccination Adherence
Authors: Syundyukov Emil , Mednis Martins , Zaharenko Linda , Pildegovica Eva , Danovska Ieva , Kistkins Svjatoslavs , Seidmann Abraham , Benis Arriel , Pirags Valdis , Tzivian Lilian
Published: December 2021

Due to the severe impact of COVID-19 on public health, rollout of the vaccines must be large-scale. Current solutions are not intended to promote an active collaboration between communities and public health researchers. We aimed to develop a digital platform for communication between scientists and the general population, and to use it for an exploratory study on factors associated with vaccination readiness. The digital platform was developed in Latvia and was equipped with dynamic consent management. During a period of six weeks 467 participants were enrolled in the population-based cross-sectional exploratory study using this platform. We assessed demographics, COVID-19-related behavioral and personal factors, and reasons for vaccination. Logistic regression models adjusted for the level of education, anxiety, factors affecting the motivation to vaccinate, and risk of infection/severe disease were built to investigate their association with vaccination readiness. In the fully adjusted multiple logistic regression model, factors associated with vaccination readiness were anxiety (odds ratio, OR = 3.09 [95% confidence interval 1.88; 5.09]), feelings of social responsibility (OR = 1.61 [1.16; 2.22]), and trust in pharmaceutical companies (OR = 1.53 [1.03; 2.27]). The assessment of a large number of participants in a six-week period show the potential of a digital platform to create a data-driven dialogue on vaccination readiness.
A Systematic Review on COVID-19 Vaccine Strategies, Their Effectiveness, and Issues
Authors: Khandker Shahad Saif , Godman Brian , Jawad Md. Irfan , Meghla Bushra Ayat , Tisha Taslima Akter , Khondoker Mohib Ullah , Haq Md. Ahsanul , Charan Jaykaran , Talukder Ali Azam , Azmuda Nafisa , Sharmin Shahana , Jamiruddin Mohd. Raeed , Haque Mainul , Adnan Nihad
Published: December 2021

COVID-19 vaccines are indispensable, with the number of cases and mortality still rising, and currently no medicines are routinely available for reducing morbidity and mortality, apart from dexamethasone, although others are being trialed and launched. To date, only a limited number of vaccines have been given emergency use authorization by the US Food and Drug Administration and the European Medicines Agency. There is a need to systematically review the existing vaccine candidates and investigate their safety, efficacy, immunogenicity, unwanted events, and limitations. The review was undertaken by searching online databases, i.e., Google Scholar, PubMed, and ScienceDirect, with finally 59 studies selected. Our findings showed several types of vaccine candidates with different strategies against SARS-CoV-2, including inactivated, mRNA-based, recombinant, and nanoparticle-based vaccines, are being developed and launched. We have compared these vaccines in terms of their efficacy, side effects, and seroconversion based on data reported in the literature. We found mRNA vaccines appeared to have better efficacy, and inactivated ones had fewer side effects and similar seroconversion in all types of vaccines. Overall, global variant surveillance and systematic tweaking of vaccines, coupled with the evaluation and administering vaccines with the same or different technology in successive doses along with homologous and heterologous prime-booster strategy, have become essential to impede the pandemic. Their effectiveness appreciably outweighs any concerns with any adverse events.
Vaccination against Cancer or Infectious Agents during Checkpoint Inhibitor Therapy
Authors: Nasti Tahseen H. , Eberhardt Christiane S.
Published: December 2021

The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic cancer vaccines is a promising option as vaccination may help to overcome resistance to immunotherapies while immunotherapies may increase immune responses to the particular cancer vaccine by reinvigorating exhausted T cells. Thus, it would be possible to reprogram a response with appropriate vaccines, using a particular cancer antigen and a corresponding ICI. Target populations include currently untreatable cancer patients or those who receive treatment regimens with high risk of serious side effects. In addition, with the increased use of ICI in clinical practice, questions arise regarding safety and efficacy of administration of conventional vaccines, such as influenza or COVID-19 vaccines, during active ICI treatment. This review discusses the main principles of prophylactic and therapeutic cancer vaccines, the potential impact on combining therapeutic cancer vaccines with ICI, and briefly summarizes the current knowledge of safety and effectiveness of influenza and COVID-19 vaccines in ICI-treated patients.
The Differences in the Level of Anti-SARS-CoV-2 Antibodies after mRNA Vaccine between Convalescent and Non-Previously Infected People Disappear after the Second Dose—Study in Healthcare Workers Group in Poland
Authors: Kwiecińska-Piróg Joanna , Przekwas Jana , Kraszewska Zuzanna , Sękowska Alicja , Brodzka Sylwia , Wiktorczyk-Kapischke Natalia , Grudlewska-Buda Katarzyna , Wałecka-Zacharska Ewa , Zacharski Maciej , Mańkowska-Cyl Aneta , Gospodarek-Komkowska Eugenia , Skowron Krzysztof
Published: December 2021

(1) Background: In many infections, antibodies play a crucial role in controlling infection. In COVID-19, the dynamics of the immune system response to SARS-CoV-2 is not fully understood. (2) Methods: The study was conducted on 120 healthcare workers from Dr. Antoni Jurasz University Hospital No. 1 in Bydgoszcz, between June and December 2020. In all participants, IgA and IgG antibody serum concentrations were measured using the semi-quantitative Anti-SARS-CoV-2 ELISA test (Euroimmun). After vaccination, in January and February 2021, antibody levels were examined using the quantitative IgG Anti-SARS-CoV-2 Quantivac ELISA test (Euroimmun). (3) Results: During the whole study period, the SARS-CoV-2 infection was confirmed in 29 (24.2%) participants. In all infected participants, IgA and IgG antibodies were detectable after infection by semi-quantitative serological tests. Levels of antibodies were higher one month after the first dose in the convalescents than in the non-previously infected participants. In this second group, the level of antibodies increased significantly after the second dose of vaccines compared to the first dose. (4) Conclusions: The level of antibodies after the first dose of vaccine in the convalescents’ group is higher than in the SARS-CoV-2 non-infected group, but the differences disappear after the second vaccination.
A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice
Authors: Li Qiao , Liu Zhihua , Liu Yi , Liang Chen , Shu Jiayi , Jin Xia , Li Chuanyou , Kou Zhihua
Published: December 2021

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.
VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants
Authors: Prates-Syed Wasim A. , Chaves Lorena C. S. , Crema Karin P. , Vuitika Larissa , Lira Aline , Côrtes Nelson , Kersten Victor , Guimarães Francisco E. G. , Sadraeian Mohammad , Barroso da Silva Fernando L. , Cabral-Marques Otávio , Barbuto José A. M. , Russo Momtchilo , Câmara Niels O. S. , Cabral-Miranda Gustavo
Published: December 2021

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.
Humoral Immune Response to SARS-CoV-2 Vaccination after a Booster Vaccine Dose in Two Kidney Transplant Recipients with Fabry Disease and Variable Secondary Immunosuppressive Regimens
Authors: Bernea Lavinia , Ailioaie Oana R. , Benhamouda Nadine , Tartour Eric , Germain Dominique P.
Published: December 2021

The urgent need to fight the COVID-19 pandemic has accelerated the development of vaccines against SARS-CoV-2 and approval processes. Initial analysis of two-dose regimens with mRNA vaccines reported up to 95% efficacy against the original strain of the SARS-CoV-2 virus. Challenges arose with the appearance of new strains of the virus, and reports that solid organ transplant recipients may have reduced vaccination success rates after a two-dose mRNA vaccination regimen encouraged health authorities to recommend a booster in immunocompromised patients. Fabry disease is an X-linked inherited lysosomal disorder, which may lead to chronic end-stage renal disease. We report on two patients with advanced Fabry disease, renal graft and adjunctive immunosuppressive therapies who exhibited variable humoral vaccination-related immune responses against SARS-CoV-2 after three vaccine doses. The first patient developed mild COVID-19 infection, while the second patient did not seroconvert after three shots of an mRNA vaccine. Both cases emphasize that patients with Fabry disease and renal graft are susceptible to develop a weak response to COVID-19 vaccination and highlight the importance of maintaining barrier protection measures. Vaccination of family members should be encouraged to lower the risk of viral transmission to immunocompromised, transplanted patients, including vaccinated ones.
Comirnaty-Elicited and Convalescent Sera Recognize Different Spike Epitopes
Authors: Hein Sascha , Benz Nuka Ivalu , Eisert Jonathan , Herrlein Marie-Luise , Oberle Doris , Dreher Michael , Stingl Julia C. , Hildt Christoph , Hildt Eberhard
Published: December 2021

Many of the approved SARS-CoV-2 vaccines are based on a stabilized variant of the spike protein. This raises the question of whether the immune response against the stabilized spike is identical to the immune response that is elicited by the native spike in the case of a SARS-CoV-2 infection. Using a peptide array-based approach, we analysed the binding of antibodies from Comirnaty-elicited, convalescent, and control sera to the peptides covering the spike protein. A total of 37 linear epitopes were identified. A total of 26 of these epitopes were almost exclusively recognized by the convalescent sera. Mapping these epitopes to the spike structures revealed that most of these 26 epitopes are masked in the pre-fusion structure. In particular, in the conserved central helix, three epitopes that are only exposed in the post-fusion conformation were identified. This indicates a higher spike-specific antibody diversity in convalescent sera. These differences could be relevant for the breadth of spike-specific immune response.
A Study on Performance Evaluation of Biodiesel from Grape Seed Oil and Its Blends for Diesel Vehicles
Authors: Fadairo Adebayo , Ip Weng Fai
Published: December 2021

With incessant increases in fuel prices worldwide and concerns for environmental pollution, the need for alternative sources of energy is becoming urgent. In this study, the potential of grape seed oil for biodiesel as an alternative fuel was evaluated. Refined grape seed oil was bought in liquid form and then subjected to an alkali-catalyzed transesterification process for biodiesel production. The physicochemical properties of the resulting biodiesel—namely, viscosity, cetane number, and heating value—were investigated. The biodiesel was blended with a conventional diesel in various proportions and combusted in a four-cylinder, four-stroke compression ignition (diesel) engine under two loading conditions. Experimental results revealed that the blend ratio of B70 (70% GS biodiesel and 30% conventional diesel) gave the best overall engine performance in terms of maximum power, minimum emissions, and fuel consumption. Furthermore, a novel neural network technique called extreme learning machine was adopted to investigate the optimal blend ratio using the dataset obtained from the experimental results. The results also indicate that the best choice of biodiesel blend ratio is approximately B73.67 (73.67% GS biodiesel and 26.33% conventional diesel). The study shows that grape seed oil could serve as a reliable source of production of quality biodiesel fuels, which could be used as an alternative to conventional diesel fuels.
Establishing and Optimizing a Bacterial Consortia for Effective Biodegradation of Petroleum Contaminants: Advancing Classical Microbiology via Experimental and Mathematical Approach
Authors: Wu Baichun , Deng Jingmin , Niu Hao , Liang Jiahao , Arslan Muhammad , Gamal El-Din Mohamed , Wang Qinghong , Guo Shaohui , Chen Chunmao
Published: December 2021

In classical microbiology, developing a high-efficiency bacterial consortium is a great challenge for faster biodegradation of petroleum contaminants. In this study, a systematic experimental and mathematical procedure was adopted to establish a bacterial consortium for the effective biodegradation of heavy oil constituents. A total of 27 bacterial consortia were established as per orthogonal experiments, using 8 petroleum-degrading bacterial strains. These bacteria were closer phylogenetic relatives of Brevundimonas sp. Tibet-IX23 (Y1), Bacillus firmus YHSA15, B. cereus MTCC 9817, B. aquimaris AT8 (Y2, Y6 and Y7), Pseudomonas alcaligenes NBRC (Y3), Microbacterium oxydans CV8.4 (Y4), Rhodococcus erythropolis SBUG 2052 (Y5), and Planococcus sp. Tibet-IX21 (Y8), and were used in different combinations. Partial correlation analysis and a general linear model hereafter were applied to investigate interspecific relationships among different strains and consortia. The Y1 bacterial species showed a remarkable synergy, whereas Y3, Y4, and Y6 displayed a strong antagonism in all consortia. Inoculation ratios of different strains significantly influenced biodegradation. An optimal consortium was constructed with Y1, Y2, Y5, Y7, and Y8, which revealed maximum degradation of 11.238 mg/mL OD600 for oil contaminants. This study provides a line of evidence that a functional consortium can be established by mathematical models for improved bioremediation of petroleum-contaminated environment.
The Slope Association Type as a Comparative Index for the Evaluation of Environmental Risks
Authors: Deumlich Detlef , Völker Lidia , Funk Roger , Koch Tobias
Published: December 2021

The topography is one of the determining site characteristics, of which the slope inclination is significant for natural science aspects, including the estimation of water erosion risk and as a criterion for agricultural subsidies. The slopes within an area vary greatly and occupy very different proportions of the area. Algorithms that take this heterogeneity into account were developed in the 1970s with the medium-scale agricultural site mapping (MMK). It also contains the slope association types (SAT, in German: “Hangneigungsflächentyp”), which classifies different slopes and summarizes them as one value per reference area. The SAT can be used across various scales and different targets. Applicability is given to soil and water conservation tasks, administrative tasks as field selection or agricultural subsidies, and over a wide range of scales from small catchments areas to whole landscape analyses. Thus, one value on an area basis characterizes an important topographic factor.
Climate-Induced Yield Losses for Winter Wheat in Henan Province, North China and Their Relationship with Circulation Anomalies
Authors: Zheng Hui , Huang Jin , Chen Jiadong
Published: December 2021

Risk analysis using climate-induced yield losses (CIYL) extracted from long-term yield data have been recognized in China, but the research focusing on the time-series characteristics of risk and the circulation signals behind yield losses still remains incomplete. To address these challenges, a case study on winter wheat production in Henan province, north China was conducted by using annual series of yield in 17 cities during 1988–2017 and monthly series of 15 types of large-scale oceanic-atmospheric circulation indices (LOACI). A comprehensive risk assessment method was established by combining the intensity, frequency, and variability of CIYL and principal component analysis (PCA). The results showed that the westernmost Henan was identified as the area of higher-risk. PCA and Mann–Kendall trend tests indicated that the southern, northern, eastern, and western areas in Henan province were classified as having different annual CIYL variations in these four sub-regions; the decreasing trend of CIYL in northern area was the most notable. Since the 2000s, a significant decline in CIYL was found in each sub-region. It should be noted that the key LOACI, which includes Tropical Northern Atlantic Index (TNA), Western Hemisphere warm pool (WHWP), and Southern oscillation index (SOI), indicated significant CIYL anomalies in some months. Furthermore, the regional yield simulation results using linear regression for the independent variables of year and various LOACI were satisfactory, with the average relative error ranging from 3.48% to 6.87%.
Proposing the Optimum Withdrawing Scenarios to Provide the Western Coastal Area of Port Said, Egypt, with Sufficient Groundwater with Less Salinity
Authors: Abdelfattah Mohamed , Abu-Bakr Heba Abdel-Aziz , Gaber Ahmed , Geriesh Mohamed H. , Elnaggar Ashraf Y. , Nahhas Nihal El , Hassan Taher Mohammed
Published: December 2021

Recently, groundwater resources in Egypt have become one of the important sources to meet human needs and activities, especially in coastal areas such as the western area of Port Said, where seawater desalination cannot be used due to the problem of oil spill and the reliance upon groundwater resources. Thus, the purpose of the study is the sustainable management of the groundwater resources in the coastal aquifer entailing groundwater abstraction. In this regard, the Visual MODFLOW and SEAWAT codes were used to simulate groundwater flow and seawater intrusion in the study area for 50 years (from 2018 to 2068) to predict the drawdown, as well as the salinity distribution due to the pumping of the wells on the groundwater coastal aquifer based on field investigation data and numerical modelling. Different well scenarios were used, such as the change in well abstraction rate, the different numbers of abstraction wells, the spacing between the abstraction wells and the change in screen depth in abstraction. The recommended scenarios were selected after comparing the predicted drawdown and salinity results for each scenario to minimize the seawater intrusion and preserve these resources from degradation.
Shallow Groundwater Quality Assessment and Its Suitability Analysis for Drinking and Irrigation Purposes
Authors: Jat Baloch Muhammad Yousuf , Zhang Wenjing , Chai Juanfen , Li Shuxin , Alqurashi Muwaffaq , Rehman Gohar , Tariq Aqil , Talpur Shakeel Ahmed , Iqbal Javed , Munir Mamoona , Hussein Enas E.
Published: December 2021

For shallow groundwater, hydrogeochemical processes and quality assessment must be addressed because shallow groundwater is freely available in many parts of the globe. Due to recent anthropogenic activities and environmental changes in Sakrand, Sindh, Pakistan, the groundwater is extremely vulnerable. To provide safe drinking and agricultural water, hydrogeochemical analysis is required. Ninety-five groundwater samples were analyzed using agricultural and drinking indices to determine the hydrogeochemical parameters using multivariate analysis such as Pearson correlations, principal component cluster analysis, as well as Piper diagrams and Gibbs plot for drinking and agricultural indices. An abundance of ions was observed through the statistical summary; however, cations and anions were recorded in the orders Na+ > Ca2+ > Mg2+ > K+ and HCO3− > Cl− > SO42− > NO3− > F−. The hydrogeochemical process used to quantify the major reactions occurring in the groundwater system showed rock dominance; the Piper diagrams evaluated the water type. A mixed pattern of calcium, magnesium, and chloride ions (Ca2+−Mg2+−Cl− type) was observed. Additionally, the ion exchange method showed an excess of bicarbonate ions due to carbonic acid weathering. The water quality index (WQI) resulted 32.6% of groundwater being unsuitable for human consumption; however, the United States Salinity Laboratory (USSL) diagram showed 60% of samples were unsuitable for irrigation due to high salinity and the Wilcox diagram depicted 5% of samples lying in the unsuitable region. Most of the water samples were suitable for drinking; only a few samples were unsafe for drinking purposes for children due to the high hazard index.
Study of Impact of Cloud-Seeding on Intensity-Duration-Frequency (IDF) Curves of Sharjah City, the United Arab Emirates
Authors: Almheiri Khalid B. , Rustum Rabee , Wright Grant , Adeloye Adebayo J.
Published: December 2021

Despite the availability of some studies related to rainfall characteristics in Sharjah city and the UAE, very few of these studies have investigated any causal link between recent cloud-seeding missions and the increasing rainfall intensities and urban floods being experienced. This study has assessed the impact of cloud-seeding operations that started in 2010 on the IDF curves of Sharjah city, The UAE. Hourly rainfall data spanning between 2010 and 2020 available at three stations, namely Sharjah Airport, Al Dhaid, and Mleiha, and provided by the National Center of Meteorology were used. To allow comparison with the pre-cloudseeding (2010) era, these records were extended back to 1992 using the much longer data available at Dubai Airport with the aid of the Self-organizing map approach. The developed IDF curves showed an apparent increase in rainfall intensities after implementing the cloud-seeding missions. In addition, the estimated mean rainfall intensities for three regions of the city were also much higher for the cloudseeded years compared to the pre-cloudseeding period. The study suggests that, while cloud-seeding provides water security benefits, its impact on urban flooding should also be carefully considered in the context of urban development plans.