bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Predator Exclusion and Habitat on Seroprevalence of New World Orthohantavirus Harbored by Two Sympatric Rodents within the Interior Atlantic Forest
Authors: Spruill-Harrell Briana , Pérez-Umphrey Anna , Valdivieso-Torres Leonardo , Cao Xueyuan , Owen Robert D. , Jonsson Colleen B.
Published: October 2021

Understanding how perturbations to trophic interactions influence virus–host dynamics is essential in the face of ongoing biodiversity loss and the continued emergence of RNA viruses and their associated zoonoses. Herein, we investigated the role of predator exclusion on rodent communities and the seroprevalence of hantaviruses within the Reserva Natural del Bosque Mbaracayú (RNBM), which is a protected area of the Interior Atlantic Forest (IAF). In the IAF, two sympatric rodent reservoirs, Akodon montensis and Oligoryzomys nigripes, harbor Jaborá and Juquitiba hantavirus (JABV, JUQV), respectively. In this study, we employed two complementary methods for predator exclusion: comprehensive fencing and trapping/removal. The goal of exclusion was to preclude the influence of predation on small mammals on the sampling grids and thereby potentially reduce rodent mortality. Following baseline sampling on three grid pairs with different habitats, we closed the grids and began predator removal. By sampling three habitat types, we controlled for habitat-specific effects, which is important for hantavirus–reservoir dynamics in neotropical ecosystems. Our six-month predator exclusion experiment revealed that the exclusion of terrestrial mammalian predators had little influence on the rodent community or the population dynamics of A. montensis and O. nigripes. Instead, fluctuations in species diversity and species abundances were influenced by sampling session and forest degradation. These results suggest that seasonality and landscape composition play dominant roles in the prevalence of hantaviruses in rodent reservoirs in the IAF ecosystem.
Novel Virulent Bacteriophage ΦSG005, Which Infects Streptococcus gordonii, Forms a Distinct Clade among Streptococcus Viruses
Authors: Fujiki Jumpei , Yoshida Shin-ichi , Nakamura Tomohiro , Nakamura Keisuke , Amano Yurika , Nishida Keita , Nishi Keitaro , Sasaki Michihito , Iwasaki Tomohito , Sawa Hirofumi , Komatsuzawa Hitoshi , Hijioka Hiroshi , Iwano Hidetomo
Published: October 2021

Bacteriophages are viruses that specifically infect bacteria and are classified as either virulent phages or temperate phages. Despite virulent phages being promising antimicrobial agents due to their bactericidal effects, the implementation of phage therapy depends on the availability of virulent phages against target bacteria. Notably, virulent phages of Streptococcus gordonii, which resides in the oral cavity and is an opportunistic pathogen that can cause periodontitis and endocarditis have previously never been found. We thus attempted to isolate virulent phages against S. gordonii. In the present study, we report for the first time a virulent bacteriophage against S. gordonii, ΦSG005, discovered from drainage water. ΦSG005 is composed of a short, non-contractile tail and a long head, revealing Podoviridae characteristics via electron microscopic analysis. In turbidity reduction assays, ΦSG005 showed efficient bactericidal effects on S. gordonii. Whole-genome sequencing showed that the virus has a DNA genome of 16,127 bp with 21 coding sequences. We identified no prophage-related elements such as integrase in the ΦSG005 genome, demonstrating that the virus is a virulent phage. Phylogenetic analysis indicated that ΦSG005 forms a distinct clade among the streptococcus viruses and is positioned next to streptococcus virus C1. Molecular characterization revealed the presence of an anti-CRISPR (Acr) IIA5-like protein in the ΦSG005 genome. These findings facilitate our understanding of streptococcus viruses and advance the development of phage therapy against S. gordonii infection.
Newcastle Disease Virus Vectored Chicken Infectious Anaemia Vaccine Induces Robust Immune Response in Chickens
Authors: Chellappa Madhan Mohan , Dey Sohini , Pathak Dinesh Chandra , Singh Asmita , Ramamurthy Narayan , Ramakrishnan Saravanan , Mariappan Asok Kumar , Dhama Kuldeep , Vakharia Vikram N.
Published: October 2021

Newcastle disease virus (NDV) strain R2B, with an altered fusion protein cleavage site, was used as a viral vector to deliver the immunogenic genes VP2 and VP1 of chicken infectious anaemia virus (CIAV) to generate a bivalent vaccine candidate against these diseases in chickens. The immunogenic genes of CIAV were expressed as a single transcriptional unit from the NDV backbone and the two CIA viral proteins were obtained as separate entities using a self-cleaving foot-and-mouth disease virus 2A protease sequence between them. The recombinant virus (rR2B-FPCS-CAV) had similar growth kinetics as that of the parent recombinant virus (rR2B-FPCS) in vitro with similar pathogenicity characteristics. The bivalent vaccine candidate when given in specific pathogen-free chickens as primary and booster doses was able to elicit robust humoral and cell-mediated immune (CMI) responses obtained in a vaccination study that was conducted over a period of 15 weeks. In an NDV and CIAV ELISA trial, there was a significant difference in the titres of antibody between vaccinated and control groups which showed slight reduction in antibody titre by 56 days of age. Hence, a second booster was administered and the antibody titres were maintained until 84 days of age. Similar trends were noticed in CMI response carried out by lymphocyte transformation test, CD4+ and CD8+ response by flow cytometry analysis and response of real time PCR analysis of cytokine genes. Birds were challenged with virulent NDV and CIAV at 84 days and there was significant reduction in the NDV shed on the 2nd and 4th days post challenge in vaccinated birds as compared to unvaccinated controls. Haematological parameters comprising PCV, TLC, PLC and PHC were estimated in birds that were challenged with CIAV that indicated a significant reduction in the blood parameters of controls. Our findings support the development and assessment of a bivalent vaccine candidate against NDV and CIAV in chickens.
Cytomegalovirus Infections in Children with Primary and Secondary Immune Deficiencies
Authors: Bateman Caroline M. , Kesson Alison , Powys Madeleine , Wong Melanie , Blyth Emily
Published: October 2021

Cytomegalovirus (CMV) is a human herpes virus that causes significant morbidity and mortality in immunosuppressed children. CMV primary infection causes a clinically mild disease in healthy children, usually in early childhood; the virus then utilises several mechanisms to establish host latency, which allows for periodic reactivation, particularly when the host is immunocompromised. It is this reactivation that is responsible for the significant morbidity and mortality in immunocompromised children. We review CMV infection in the primary immunodeficient host, including early identification of these infants by newborn screening to allow for CMV infection prevention strategies. Furthermore, clinical CMV is discussed in the context of children treated with secondary immunodeficiency, particularly paediatric cancer patients and children undergoing haematopoietic stem cell transplant (HSCT). Treatments for CMV are highlighted and include CMV immunotherapy.
Utilizing the VirIdAl Pipeline to Search for Viruses in the Metagenomic Data of Bat Samples
Authors: Budkina Anna Y. , Korneenko Elena V. , Kotov Ivan A. , Kiselev Daniil A. , Artyushin Ilya V. , Speranskaya Anna S. , Khafizov Kamil , Akimkin Vasily G.
Published: October 2021

According to various estimates, only a small percentage of existing viruses have been discovered, naturally much less being represented in the genomic databases. High-throughput sequencing technologies develop rapidly, empowering large-scale screening of various biological samples for the presence of pathogen-associated nucleotide sequences, but many organisms are yet to be attributed specific loci for identification. This problem particularly impedes viral screening, due to vast heterogeneity in viral genomes. In this paper, we present a new bioinformatic pipeline, VirIdAl, for detecting and identifying viral pathogens in sequencing data. We also demonstrate the utility of the new software by applying it to viral screening of the feces of bats collected in the Moscow region, which revealed a significant variety of viruses associated with bats, insects, plants, and protozoa. The presence of alpha and beta coronavirus reads, including the MERS-like bat virus, deserves a special mention, as it once again indicates that bats are indeed reservoirs for many viral pathogens. In addition, it was shown that alignment-based methods were unable to identify the taxon for a large proportion of reads, and we additionally applied other approaches, showing that they can further reveal the presence of viral agents in sequencing data. However, the incompleteness of viral databases remains a significant problem in the studies of viral diversity, and therefore necessitates the use of combined approaches, including those based on machine learning methods.
An Opportunistic Survey Reveals an Unexpected Coronavirus Diversity Hotspot in North America
Authors: Ip Hon S. , Griffin Kathryn M. , Messer Jeffrey D. , Winzeler Megan E. , Shriner Susan A. , Killian Mary Lea , K. Torchetti Mia , DeLiberto Thomas J. , Amman Brian R. , Cossaboom Caitlin M. , Harvey R. Reid , Wendling Natalie M. , Rettler Hannah , Taylor Dean , Towner Jonathan S. , Barton Behravesh Casey , Blehert David S.
Published: October 2021

In summer 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was detected on mink farms in Utah. An interagency One Health response was initiated to assess the extent of the outbreak and included sampling animals from on or near affected mink farms and testing them for SARS-CoV-2 and non-SARS coronaviruses. Among the 365 animals sampled, including domestic cats, mink, rodents, raccoons, and skunks, 261 (72%) of the animals harbored at least one coronavirus. Among the samples that could be further characterized, 127 alphacoronaviruses and 88 betacoronaviruses (including 74 detections of SARS-CoV-2 in mink) were identified. Moreover, at least 10% (n = 27) of the coronavirus-positive animals were found to be co-infected with more than one coronavirus. Our findings indicate an unexpectedly high prevalence of coronavirus among the domestic and wild free-roaming animals tested on mink farms. These results raise the possibility that mink farms could be potential hot spots for future trans-species viral spillover and the emergence of new pandemic coronaviruses.
Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells
Authors: Kim Eun Seon , Jeon Min-Tae , Kim Kyu-Sung , Lee Suji , Kim Suji , Kim Do-Geun
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.
Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids
Authors: Hartmann Samantha R. , Goetschius Daniel J. , Hu Jiafen , Graff Joshua J. , Bator Carol M. , Christensen Neil D. , Hafenstein Susan L.
Published: October 2021

Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. However, studies have been hampered due to restricted tropism that makes production and purification of high titer virus problematic. This issue has been overcome by developing alternative HPV production methods such as virus-like particles (VLPs), which are devoid of a native viral genome. Structural studies have been limited in resolution due to the heterogeneity, fragility, and stability of the VLP capsids. The mouse papillomavirus (MmuPV1) presented here has provided the opportunity to study a native papillomavirus in the context of a common laboratory animal. Using cryo EM to solve the structure of MmuPV1, we achieved 3.3 Å resolution with a local symmetry refinement method that defined smaller, symmetry related subparticles. The resulting high-resolution structure allowed us to build the MmuPV1 asymmetric unit for the first time and identify putative L2 density. We also used our program ISECC to quantify capsid flexibility, which revealed that capsomers move as rigid bodies connected by flexible linkers. The MmuPV1 flexibility was comparable to that of a HPV VLP previously characterized. The resulting MmuPV1 structure is a promising step forward in the study of papillomavirus and will provide a framework for continuing biochemical, genetic, and biophysical research for papillomaviruses.
Expression of an Antiviral Gene GmRUN1 from Soybean Is Regulated via Intron-Mediated Enhancement (IME)
Authors: Diao Pengfei , Sun Hongyu , Bao Zhuo , Li Wenxia , Niu Niu , Li Weimin , Wuriyanghan Hada
Published: October 2021

Most of R (resistance) genes encode the protein containing NBS-LRR (nucleotide binding site and leucine-rich repeat) domains. Here, N. benthamiana plants were used for transient expression assays at 3–4 weeks of age. We identified a TNL (TIR-NBS-LRR) encoding gene GmRUN1 that was resistant to both soybean mosaic virus (SMV) and tobacco mosaic virus (TMV). Truncation analysis indicated the importance of all three canonical domains for GmRUN1-mediated antiviral activity. Promoter-GUS analysis showed that GmRUN1 expression is inducible by both salicylic acid (SA) and a transcription factor GmDREB3 via the cis-elements as-1 and ERE (ethylene response element), which are present in its promoter region. Interestingly, GmRUN1 gDNA (genomic DNA) shows higher viral resistance than its cDNA (complementary DNA), indicating the existence of intron-mediated enhancement (IME) for GmRUN1 regulation. We provided evidence that intron2 of GmRUN1 increased the mRNA level of native gene GmRUN1, a soybean antiviral gene SRC7 and also a reporter gene Luciferase, indicating the general transcriptional enhancement of intron2 in different genes. In summary, we identified an antiviral TNL type soybean gene GmRUN1, expression of which was regulated at different layers. The investigation of GmRUN1 gene regulatory network would help to explore the mechanism underlying soybean-SMV interactions.
Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Children and Adolescents: A Systematic Review
Authors: Lv Meng , Luo Xufei , Shen Quan , Lei Ruobing , Liu Xiao , Liu Enmei , Li Qiu , Chen Yaolong
Published: October 2021

Aim: To identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccines in children and adolescents. Methods: We conducted a systematic review of published studies and ongoing clinical studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged < 18 years). Databases including PubMed, Web of Science, WHO COVID-19 database, and China National Knowledge Infrastructure (CNKI) were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to identify ongoing studies. Results: Eight published studies with a total of 2852 children and adolescents and 28 ongoing clinical studies were included. Of the eight published studies, two were RCTs, two case series, and four case reports. The investigated COVID-19 vaccines had good safety profiles in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. A limited number of cases of myocarditis and pericarditis were reported. The RCTs showed that the immune response to BNT162b2 in adolescents aged 12–15 years was non-inferior to that in young people aged 16–25 years, while with 3 μg CoronaVac injection the immune response was stronger than with 1.5 μg. The efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100), based on one RCT. Of the 28 ongoing clinical studies, twenty-three were interventional studies. The interventional studies were being conducted in fifteen countries, among them, China (10, 43.5%) and United States(9, 39.1%) had the highest number of ongoing trials. BNT162b2 was the most commonly studied vaccine in the ongoing trials. Conclusion: Two COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical studies of the COVID-19 vaccination in children and adolescents with longer follow-up time, larger sample size, and a greater variety of vaccines are still urgently needed.
Pulmonary Infection Caused by Mycobacterium malmoense in a Chronic HIV-Infected Individual Participating in a Therapeutic Vaccine Trial
Authors: Marques Joana Silva , Bodro Marta , Torres Berta , García Felipe , Martínez José Antonio , Leal Lorna
Published: October 2021

We report a case of Mycobacterium malmoense pulmonary infection and HIV-1 chronic co-infection in a 60-year-old man while participating in an HIV-1 therapeutic vaccine clinical trial and during the analytical treatment interruption. We present clinical and therapeutic features of a complicated M. malmoense pulmonary infection along with discussion of the possible relation to the HIV-1 cure-related interventions.
Flu and Tdap Maternal Immunization Hesitancy in Times of COVID-19: An Italian Survey on Multiethnic Sample
Authors: Cavaliere Anna Franca , Zaami Simona , Pallottini Marta , Perelli Federica , Vidiri Annalisa , Marinelli Enrico , Straface Gianluca , Signore Fabrizio , Scambia Giovanni , Marchi Laura
Published: October 2021

Background: Tdap and flu immunization in pregnancy has been proven to be both effective and safe. Despite this, the vaccination rate in pregnant women is low in Italy. The COVID-19 pandemic has focused the attention of public opinion on communicable diseases, underlining the importance of primary prevention measures such as vaccination. We conducted a survey to investigate the behavior of pregnant women during the COVID-19 pandemic regarding maternal immunization to identify the reasons for vaccine hesitancy in order to overcome them. The new challenge is COVID-19 vaccination in pregnancy, and preliminary data show hesitancy towards it. Our analysis may be useful to improve immunization in the pregnant population, including through the COVID-19 vaccine. Methods: A targeted survey was performed in Italy including 520 women who experienced in the first trimester of pregnancy, prior to the novel coronavirus spread, the 2019–2020 influenza vaccination campaign and the Tdap vaccine recommendation in the third trimester during the COVID pandemic. They represent a unique model to investigate if the new coronavirus outbreak might have changed attitudes towards vaccination in pregnancy in the same patients. Data were collected from a self-completed paper questionnaire. Descriptive statistics were calculated and percentages were compared using the chi-2 test or Fisher’s exact test. Results: We obtained data from 195 of the 520 women who gave birth during the inclusion period; 325 cases declined to participate in the survey. A total of 8.7% (17 cases) performed flu vaccination in the first trimester of pregnancy (pre-COVID era), 50.8% (99 cases) accepted Tdap immunization during their third trimester of gestation (COVID-19 pandemic) and 6.7% (13 cases) received both vaccines during pregnancy. For both the flu and Tdap shots, pregnant patients were more likely to accept the vaccines if they were recommended by a healthcare provider, whereas the main reason not to be vaccinated was the lack of such a recommendation. Conclusions: Our survey shows that the COVID-19 experience, which has raised awareness as to the role of vaccines in preventable diseases, may positively change attitudes toward immunization in pregnancy. Vaccination must be recommended to all pregnant women and organized during routine prenatal care as an important element for the prevention of communicable diseases. Vaccination hesitancy can be minimized through consistent recommendation to all pregnant women offered by obstetric staff during routine prenatal care. This approach is likely to be effective in terms of building trust in flu and Tdpa immunization among pregnant women, as well as to avoid unjustified hesitancy towards the more recent COVID-19 vaccines.
Factors Associated with COVID-19 Vaccine Intentions in Eastern Zimbabwe: A Cross-Sectional Study
Authors: McAbee Lauren , Tapera Oscar , Kanyangarara Mufaro
Published: October 2021

Vaccines are one of the most effective public health strategies to protect against infectious diseases, yet vaccine hesitancy has emerged as a global health threat. Understanding COVID-19 knowledge and attitudes and their association with vaccine intentions can help the targeting of strategies to increase vaccination uptake and achieve herd immunity. The goal of this study was to assess COVID-19 knowledge, attitudes, and behaviors, and identify factors associated with COVID-19 vaccine intentions among heads of households in Manicaland Province, Zimbabwe. A cross-sectional survey was conducted in May 2021 among 551 randomly selected households. Data were collected on socio-demographic characteristics, and knowledge, attitudes, and behaviors regarding COVID-19 and the vaccines. More than half (55.7%) of the respondents reported intending to vaccinate themselves or their households. Multivariate logistic regression indicated that the likelihood of vaccine intentions was most strongly associated with confidence in vaccine safety. Additionally, the odds of intending to get vaccinated were significantly higher among heads of households who were male, had a higher level of education, and identified vaccination and face mask usage as prevention measures. Among perceived motivators to vaccinate, recommendations from the World Health Organization and availability of the vaccine free of charge increased the likelihood of vaccine intentions, while country of vaccine manufacturer posed a barrier to vaccine intentions. As the vaccine rollout in Zimbabwe continues, efforts to increase COVID-19 vaccination coverage and achieve herd immunity should target females and less educated populations and be tailored to address concerns about vaccine safety and country of manufacturer.
Direct and Indirect Proof of SARS-CoV-2 Infections in Indigenous Wiwa Communities in North-Eastern Colombia—A Cross-Sectional Assessment Providing Preliminary Surveillance Data
Authors: Concha Gustavo , Frickmann Hagen , Oey Anke , Strengert Monika , Kreienbrock Lothar , Kann Simone
Published: October 2021

To provide initial data on local SARS-CoV-2 epidemiology and spread in indigenous communities in north-eastern Colombia, respiratory swabs and serum samples from volunteers of indigenous communities were examined in March and April 2021. Samples from non-indigenous Colombians from the same villages were included as well. While previous exposure to SARS-CoV-2 was assessed by analysing serum samples for IgG and IgM with a rapid antibody point-of-care-test (POCT), screening for active infections was carried out with an antigen POCT test and real-time PCR from nasal swabs. In 380 indigenous and 72 non-indigenous volunteers, 61 (13.5%) active infections and an additional 113 (25%) previous infections were identified using diagnostic serology and molecular assays. Previous infections were more frequent in non-indigenous volunteers, and relevant associations of clinical features with active or previous SARS-CoV-2 infections were not observed. Symptoms reported were mild to moderate. SARS-CoV-2 was frequent in the assessed Colombian indigenous communities, as 38.5% of the study participants showed signs of exposure to SARS-CoV-2, which confirms the need to include these indigenous communities in screening and vaccination programs.
A Rapid Systematic Review of Factors Influencing COVID-19 Vaccination Uptake in Minority Ethnic Groups in the UK
Authors: Kamal Atiya , Hodson Ava , Pearce Julia M.
Published: October 2021

COVID-19 has disproportionately affected minority ethnic groups in the United Kingdom. To maximise the effectiveness of the vaccination programme, it is important to understand and address disparities in vaccine uptake. The aim of this review was to identify factors influencing COVID-19 vaccination uptake between minority ethnic groups in the UK. A search was undertaken in peer-reviewed databases, polling websites and grey literature from January 2020–May 2021. Studies were included if they reported data on vaccine uptake or the reasons for or against accepting the COVID-19 vaccination for minority ethnic groups in the UK. Twenty-one papers met the inclusion criteria, all of which were rated as either good or moderate quality. Ethnic minority status was associated with higher vaccine hesitancy and lower vaccine uptake compared with White British groups. Barriers included pre-existing mistrust of formal services, lack of information about the vaccine’s safety, misinformation, inaccessible communications, and logistical issues. Facilitators included inclusive communications which address vaccine concerns via trusted communicators and increased visibility of minority ethnic groups in the media. Community engagement to address the concerns and informational needs of minority ethnic groups using trusted and collaborative community and healthcare networks is likely to increase vaccine equity and uptake.
Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation
Authors: Caucci Sara , Corvaro Benedetta , Tiano Sofia Maria Luigia , Valenza Anna , Longo Roberta , Marinelli Katia , Ferreri Monica Lucia , Spiridigliozzi Patrik , Salvoni Giovanna , Bagnarelli Patrizia , Menzo Stefano
Published: October 2021

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.
Antibody Persistence 6 Months Post-Vaccination with BNT162b2 among Health Care Workers
Authors: Campo Flaminia , Venuti Aldo , Pimpinelli Fulvia , Abril Elva , Blandino Giovanni , Conti Laura , De Virgilio Armando , De Marco Federico , Di Noia Vincenzo , Di Domenico Enea Gino , Di Martino Simona , Ensoli Fabrizio , Giannarelli Diana , Mandoj Chiara , Mazzola Francesco , Moretto Silvia , Petruzzi Gerardo , Petrone Fabrizio , Pichi Barbara , Pontone Martina , Vidiri Antonello , Vujovic Branka , Piaggio Giulia , Sperandio Eleonora , Rosati Valentina , Cognetti Francesco , Morrone Aldo , Ciliberto Gennaro , Pellini Raul
Published: October 2021

Background: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. Methods: An immunogenicity evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. Results: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53–339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. Conclusions: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.
To Vaccinate or Not: Impact of Bovine Viral Diarrhoea in French Cow-Calf Herds
Authors: Arnoux Sandie , Bidan Fabrice , Damman Alix , Petit Etienne , Assié Sébastien , Ezanno Pauline
Published: October 2021

Bovine viral diarrhoea (BVD) remains an issue despite control programs implemented worldwide. Virus introduction can occur through contacts with neighbouring herds. Vaccination can locally protect exposed herds. However, virus spread depends on herd characteristics, which may impair vaccination efficiency. Using a within-herd epidemiological model, we compared three French cow-calf farming systems named by their main breed: Charolaise, Limousine, and Blonde d’Aquitaine. We assessed vaccination strategies of breeding females assuming two possible protections: against infection or against vertical transmission. Four commercial vaccines were considered: Bovilis®, Bovela®, Rispoval®, and Mucosiffa®. We tested various virus introduction frequency in a naïve herd. We calculated BVD economic impact and vaccination reward. In Charolaise, BVD economic impact was 113€ per cow over 5 years after virus introduction. Irrespective of the vaccine and for a high enough risk of introduction, the yearly expected reward was 0.80€ per invested euro per cow. Vaccination should not be stopped before herd exposure has been decreased. In contrast, the reward was almost nil in Blonde d’Aquitaine and Limousine. This highlights the importance of accounting for herd specificities to assess BVD impact and vaccination efficiency. To guide farmers’ vaccination decisions against BVD, we transformed this model into a French decision support tool.
Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine
Authors: Porier Danielle L. , Wilson Sarah N. , Auguste Dawn I. , Leber Andrew , Coutermarsh-Ott Sheryl , Allen Irving C. , Caswell Clayton C. , Budnick James A. , Bassaganya-Riera Josep , Hontecillas Raquel , Weger-Lucarelli James , Weaver Scott C. , Auguste Albert J.
Published: October 2021

Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.
Blocking HIF to Enhance NK Cells: Hints for New Anti-Tumor Therapeutic Strategies?
Authors: Vitale Massimo , Parodi Monica
Published: October 2021

Natural Killer (NK) cells are becoming an ever more promising tool to design new anti-tumor strategies. However, two major issues are still a challenge to obtain versatile and effective NK-based therapies: the way to maximize the persistency of powerful NK effectors in the patient, and the way to overcome the multiple escape mechanisms that keep away or suppress NK cells at the tumor site. In this regard, targeting the hypoxia-inducible factors (HIFs), which is important for both tumor progression and immune suppression, may be an opportunity. Especially, in the context of the ongoing studies focused on more effective NK-based therapeutic products.
Comparing the Clinical and Economic Outcomes Associated with Adjuvanted versus High-Dose Trivalent Influenza Vaccine among Adults Aged ≥ 65 Years in the US during the 2019–20 Influenza Season—A Retrospective Cohort Analysis
Authors: Levin Myron J. , Divino Victoria , Shah Drishti , DeKoven Mitch , Mould-Quevedo Joaquin , Pelton Stephen I. , Postma Maarten J.
Published: October 2021

The burden of influenza is disproportionally higher among older adults. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent (aIIV3) compared to high-dose trivalent influenza vaccine (HD-IIV3e) against influenza and cardio-respiratory disease (CRD)-related hospitalizations/ER visits among adults ≥65 years during the 2019–2020 influenza season. Economic outcomes were also compared. A retrospective cohort analysis was conducted using prescription, professional fee claims, and hospital data. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding. IPTW-adjusted Poisson regression was used to evaluate the adjusted rVE of aIIV3 versus HD-IIV3e. All-cause and influenza-related healthcare resource utilization (HCRU) and costs were examined post-IPTW. Recycled predictions from generalized linear models were used to estimate adjusted costs. Adjusted analysis showed that aIIV3 (n = 798,987) was similarly effective compared to HD-IIV3e (n = 1,655,979) in preventing influenza-related hospitalizations/ER visits (rVE 3.1%; 95% CI: −2.8%; 8.6%), hospitalizations due to any cause (−0.7%; 95% CI: −1.6%; 0.3%), and any CRD-related hospitalization/ER visit (0.9%; 95% CI: 0.01%; 1.7%). Adjusted HCRU and annualized costs were also statistically insignificant between the two cohorts. The adjusted clinical and economic outcomes evaluated in this study were comparable between aIIV3 and HD-IIV3e during the 2019–2020 influenza season.
COVID-19 Vaccination Attitudes, Perceptions, and Side Effect Experiences in Malaysia: Do Age, Gender, and Vaccine Type Matter?
Authors: Elnaem Mohamed Hassan , Mohd Taufek Nor Hidayah , Ab Rahman Norny Syafinaz , Mohd Nazar Nor Ilyani , Zin Che Suraya , Nuffer Wesley , Turner Christopher John
Published: October 2021

This study aimed to investigate the attitudes, perceptions, and experiences of side effects with the COVID-19 vaccines in Malaysia among participants in the National Vaccination Program. A cross-sectional survey was conducted among a sample of vaccine-eligible and vaccinated individuals in Malaysia between May and July 2021. A total of 428 respondents completed the survey. A vast majority (98.6%) of the respondents had registered to be vaccinated. Twenty participants (4.7%) expressed concerns about either registering or receiving the COVID-19 vaccination, mainly due to their uncertainty of vaccine safety. Approximately 77.5% received their vaccinations. Of them, 76.8% had experienced vaccine-related side effects. About 40% of the side effects occurred more with the second dose, particularly those who received the Pfizer-BioNTech vaccine (p < 0.001). Pain at the injection site (61.1%) and tiredness (48.8%) were the most reported side effects. Compared to those aged ≥60 years, all age groups were more likely to exhibit vaccine-related side effects; meanwhile, males (OR: 0.51, 95% CI: 0.27–0.93) were less likely to experience side effects than females. Those who received the Sinovac vaccine were at lower risk of experiencing side effects (OR: 0.08, 95% CI: 0.03–0.22) and were more likely to report fewer side effects than Pfizer-BioNTech (p = 0.012) and Oxford-AstraZeneca groups (p= 0.001). The overall attitudes toward the COVID-19 vaccination program were positive. Several differences in the experiences of vaccine-related side effects, in terms of prevalence and numbers, were attributed to age, gender, and received vaccine type.
Exploration of the Experience of Care Home Managers of COVID-19 Vaccination Programme Implementation and Uptake by Residents and Staff in Care Homes in Northern Ireland
Authors: Craig Linda , Haloub Radi , Reid Heather , Masson Dalrene , Mccalmont Hannah , Fodey Kathy , Conway Barbara R. , Lattyak William J. , Lattyak Elizabeth A. , Bain Amie , Al-Azzam Sayer , Aldeyab Mamoon A.
Published: October 2021

The Coronavirus 2019 (COVID-19) pandemic disproportionately affected people living and working in care homes. This study aimed to explore the experience of care home managers on the implementation and uptake of the COVID-19 vaccination programme by residents and staff in care homes in Northern Ireland. An exploratory mixed methods approach was used, i.e., semi-structured interviews to design the cross-sectional survey and content analysis of statements using open ended questions. Care home managers were approached and sixty-seven valid quantitative and forty-nine descriptive responses were analysed. The study identified eight themes which described factors that motivated residents (family visits and relationship with managers and staff), and staff vaccine uptake (return to normal life at work and trust in care home managers). The identified themes also confirmed that vaccine uptake is negatively influenced by perceived side effects. The findings indicated that social media can promote or decelerate the uptake of vaccine despite the accessibility to a successful vaccination programme. The study highlights the important role of managers in handling the challenges through building trust and establishing relationships with staff and residents. The findings identified challenges to the uptake of the COVID-19 vaccine by staff and residents that can inform the implementation of future vaccination programmes.
Fusion Expression and Immune Effect of PCV2 Cap Protein Tandem Multiantigen Epitopes with CD154/GM-CSF
Authors: Mao Qian , Zhang Weijian , Ma Shengming , Qiu Zilong , Li Bingke , Xu Chen , He Huangyu , Fan Shuangqi , Wu Keke , Chen Jinding , Zhao Mingqiu
Published: October 2021

Porcine circovirus associated diseases (PCVAD) is a contagious disease of swine caused by porcine circovirus type 2 (PCV2). The capsid protein (Cap) is the sole structural protein and the main antigen of PCV2. Cap is the principal immunogenic protein and induces humoral and cellular immunity. CD154 and GM-CSF are immune adjuvants that enhance responses to vaccines. However, whether these two cellular molecules could produce an enhanced effect in PCV2 vaccines still needs to be further studied. The results of PCR and restriction enzyme showed that the recombinant lentiviral plasmids pCDH-TB-Cap, pCDH-TB-Cap-CD154 and pCDH-TB-Cap were successfully constructed. Western blot and IFA showed that the three fusion proteins TB-Cap, TB-Cap-CD154 and TB-Cap-GM-CSF were stably expressed in CHO-K1 cells. Indirect ELISA assay showed that mice immunized with TB-Cap-CD154 and TB-Cap-GM-CSF fusion proteins produced higher PCV2-specific antibodies than mice immunized with the TB-Cap and a commercial vaccine (p < 0.0001). Moreover, lymphocyte proliferation and flow cytometry showed that the cellular immune response of each immune group was significantly enhanced (p < 0.0001). After PCV2 challenge, the results revealed that the viral loads in serum, lung and kidney of all vaccinated groups were significantly lower than the PBS group (p < 0.0001). The transcription levels of IL-2, IFN-gamma, IL-4 and IL-10 cytokines in the TB-Cap, TB-Cap-CD154 and TB-Cap-GM-CSF groups were significantly higher than those in the PBS and recombinant vaccine groups (p < 0.0001). These results indicated that CD154 and GM-CSF could enhance the ability of TB-Cap protein to induce the body to produce PCV2 specific antibodies and increase the transcription level of cytokines. Thus, CD154 and GM-CSF molecules were a powerful immunoadjuvant for PCV2 subunit vaccines. The novel TB-Cap-CD154 and TB-Cap-GM-CSF subunit vaccine has the potential to be used for the prevention and control of PCVAD.
Teladorsagia Circumcincta Galectin-Mucosal Interactome in Sheep
Authors: Hafidi Nur Nasuha , Swan Jaclyn , Faou Pierre , Lowe Rohan , Rajapaksha Harinda , Cairns Callum , Stear Michael , Beddoe Travis
Published: October 2021

Teladorsagia circumcincta is the most important gastrointestinal parasite in the livestock industry in temperate regions around the world, causing great economic losses. The infective third-stage larvae (L3) of Teladorsagia circumcincta secrete a large number of excretory-secretory (E/S) molecules, some of which are likely to play critical roles in modulating the host immune response. One of the most abundant E/S molecules is a protein termed Tci-gal-1, which has similarity to mammalian galectins. Galectins are a family of carbohydrate-binding molecules, with characteristic domain organisation and affinity for β-galactosids that mediate a variety of important cellular functions including inflammation and immune responses. To understand the role of Tci-gal-1 at the host–parasite interface, we used a proteomics pull-down approach to identify Tc-gal-1 interacting proteins from sheep abomasal scrapes and whole tissue. A total of 135 unique proteins were identified from whole abomasal tissue samples, while 89 proteins were isolated from abomasal scrape samples. Of these proteins, 63 were present in both samples. Many of the host proteins identified, such as trefoil factors and mucin-like proteins, play critical roles in the host response. The identification of Tci-gal-1 binding partners provides new insights on host–parasite interactions and could lead to the development of new control strategies.
Development of a Simple Single-Acupoint Electroacupuncture Frame and Evaluation of the Acupuncture Effect in Rabbits
Authors: Huang Huan , Zhang Jianrong , Gui Fuxing , Liu Sheng , Zhong Chonghua , Wang Tingting , Du Hongxu , He Xianlin , Cao Liting
Published: October 2021

To reduce the circulation path of the output current of traditional electroacupuncture (TEA) process in the body, a simple single-acupoint electroacupuncture (SEA) frame was designed and the acupuncture effect of SEA was evaluated through Hou-san-li (ST-36) and Qian-san-li (LI-10) acupoints. Forty-two healthy New Zealand rabbits were randomly divided into seven groups and underwent acupuncture for 20 min in an awake state. Blood samples aseptically collected from the ear vein 3 h before acupuncture and 0, 3, 6, 9, 12 and 24 h after acupuncture were used for the detection of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase MB (CK-MB) and motilin (MTL) in serum. The simple SEA frame was developed successfully, and the acupuncture results showed that the serum AST and ALT levels were significantly higher at 3 h after TEA with high frequency (p < 0.01) compared with the control group. Regarding serum CK-MB levels, no significant differences were found after SEA or TEA stimulation (p > 0.05). Serum MTL levels were significantly increased at 0 h after SEA and TEA (p < 0.05), but there were no significant differences at other time points after SEA and TEA treatment (p > 0.05). SEA not only maintains the effect of TEA but also shortens the circulation loop of the electroacupuncture (EA) current in the body, which effectively avoids body injury.
Protective Effect of Natural Antioxidant Compounds on Methimazole Induced Oxidative Stress in a Feline Kidney Epithelial Cell Line (CRFK)
Authors: Girolami Flavia , Candellone Alessia , Jarriyawattanachaikul Watanya , Meineri Giorgia , Nebbia Carlo , Badino Paola
Published: October 2021

The treatment of choice for feline hyperthyroidism is the administration of the antithyroid drug methimazole. Both the endocrinopathy and the drug adverse reactions (e.g., hepatotoxicosis, gastrointestinal disorders, and renal injury) are partly due to oxidative stress and redox unbalance. This study investigated the free radical production and the impairment of the antioxidant barrier induced by methimazole in an in vitro model of feline renal epithelium. The protective effects of quercetin and resveratrol were also explored. CRFK cells were incubated with a methimazole concentration equivalent to the maximum plasma levels in orally treated cats (4 µM), in the presence or absence of either one of the two selected antioxidants at different time-points (up to 72 h). Cell viability, ROS production, GSH levels, and mRNA expression of antioxidant enzymes (i.e., CAT, SOD, GPx, and GST) were assessed. Methimazole impaired cell viability and increased ROS levels in a time-dependent manner. Similarly, GSH content and CAT, SOD, and GPx3 expression were higher compared with control cells. Such effects were significantly counteracted by quercetin. These results provide new insights about the mechanisms underlying the methimazole-related side effects frequently observed in hyperthyroid cats. They also support the use of quercetin in the management of feline hyperthyroidism.