Search Results (64)

Background: Children are at high risk of influenza infections and may spread the disease to vulnerable family members. Quadrivalent influenza vaccines (QIV) provide protection against four strains of influenza recommended annually by the World Health Organization (WHO) and have the potential to provide improved protection during seasons with B-strain mismatch between vaccine and circulating virus strains. Methods: We evaluated the reactogenicity and safety of a QIV (Afluria Quad and Afluria Quad Junior, Seqirus, Parkville, Australia) in children aged 6 months to <3 years and 3 to <9 years over two Southern Hemisphere influenza seasons (2019 and 2020). The rates of solicited local and systemic adverse events (AEs) occurring on Days 1–7 after each vaccine dose were compared between three vaccine batches during each of the two seasons. Results: Overall, 73.7% of participants aged 6 months to <3 years and 77.5% of those aged 3 to <9 years reported any solicited AE between Day 1 and 7 of SH2019, and 66.7% and 69.2%, respectively, reported any solicited AE in SH2020, consistent with results from prior paediatric studies of QIV. The majority of solicited AEs were mild to moderate in severity. No consistent patterns of batch variation in solicited local or systemic reactogenicity were observed, suggesting no clinically significant differences between vaccine batches. No serious AEs or AEs of special interest (i.e., anaphylactic reaction or febrile convulsion) were reported during Days 1–7 after each vaccination, and no new safety concerns were identified. Conclusions: Together, these results support a clinically acceptable safety and tolerability profile of QIV in children aged 6 months to <9 years. Full article

Cattle marketed through auction market systems and/or that remain unvaccinated are considered higher risk for BRD, but impacts on host response remain unclear. We sought to identify specific genomic patterns of beef calves vaccinated against BRD viruses or not and commercially marketed or directly transported in a split-plot randomized controlled trial. Forty-one calves who remained clinically healthy from birth through backgrounding were selected (randomly stratified) from a larger cohort of cattle (n = 81). Treatment groups included VAX/DIRECT (n = 12), VAX/AUCTION (n = 11), NOVAX/DIRECT (n = 7), and NOVAX/AUCTION (n = 11). Blood RNA was acquired across five time points, sequenced, and bioinformatically processed via HISAT2 and StringTie2. Significant transcriptional changes (FDR < 0.05) were observed at backgrounding entry (T5) in NOVAX/AUCTION cattle exhibiting 2809 uniquely differentially expressed genes and relative activation of immune, inflammatory, and metabolic pathways with upregulation of interferon-stimulated genes (e.g., IFIT3, MX2, and TRIM25) and downregulation of specialized proresolving mediator (SPM) enzymes (ALOX5 and ALOX15). VAX/AUCTION cattle exhibited modulated immune activation and preserved expression of SPM-associated genes when compared to NOVAX/AUCTION cattle. Both marketing route and vaccination shape the molecular immune landscape during high-stress transitions, with preweaning vaccination potentially modulating this response. This study provides mechanistic insight into how management practices influence immunological resilience and highlights the value of integrating transcriptomics into BRD risk mitigation. Full article

Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Results: Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. Conclusions: Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol. Full article

Background: Influenza is a serious contagious disease caused by influenza virus. It is particularly dangerous for children, potentially leading to severe and even fatal complications. The aim of this study was to evaluate the safety and immunogenicity of two candidate quadrivalent influenza subunit vaccines in children aged 6–35 months. Methods: The subjects were randomly divided into three groups at a 1:1:1 ratio and received the corresponding vaccines: QIV-Sub-HD (Quadrivalent Influenza Subunit Vaccine, High Dose), QIV-Sub-LD (Quadrivalent Influenza Subunit Vaccine, Low Dose) and QIV-Split-LD (Quadrivalent Influenza Split-Virion Vaccine, Low Dose). Adverse events were recorded at 30 min, 0–7 days and 8–28 and 30 days after each dose of immunization. Serious adverse events (SAEs) were collected and reported within 6 months after the full vaccination. Blood samples were collected before the first dose and on 28 days, 3 months and 6 months after full vaccination for antibody detection to evaluate the immunogenicity and duration of immune responses. Results: The results showed that the relative and absolute criteria met the goals set by the clinical trial protocol, indicating that both vaccines are immunogenic. From the first dose to 30 days after full vaccination, the total incidence of adverse reactions in the QIV-Sub-HD, QIV-Sub-LD and QIV-Split-LD groups was 29.64%, 33.33% and 29.64%, respectively. The main symptoms were fever, cough, diarrhea and vomiting. No new safety concerns were identified. Conclusions: The quadrivalent influenza subunit vaccines candidate, manufactured by Ab&B Bio-tech Co., Ltd. JS., are safe and immunogenic in children aged 6–35 months. Full article

Background/Objectives: Influenza is a viral infection affecting up to 20% of the general population annually. Solid organ transplant recipients have a higher morbidity and mortality risk, as well as a greater likelihood of severe disease complications. Vaccination against the influenza virus is a safe and recommended prophylaxis; however, immunosuppression and high comorbidity burdens impair the immune response. We assessed the efficacy, safety, and humoral response to influenza vaccine in a population of kidney transplant recipients (KTx). Methods: Adult KTx recipients at least 6 months post-KTx were divided into vaccinated (vKTx) and non-vaccinated (nvKTx) groups based on consent for vaccination. The vKTx group received one dose of quadrivalent split virion inactivated vaccine (Vaxigrip Tetra Sanofi Pasteur). Subjective symptoms and side effects were recorded in paper journals. Antibody levels were assessed with ELISA prior to and 3 months following vaccination. Serum creatinine and proteinuria were assessed prior to vaccination as well as 3 and 6 months after. Results: Of 450 recruited KTx recipients, 91 in the vKTx group and 36 in the nvKTx group of comparable age, KTx vintage, and graft function were included in the study. Graft function and proteinuria remained stable in both groups. The vKTx group experienced no severe adverse events. The most common complaints were general malaise (20.5%) and injection site pain (10.3%). Overall infection rates were comparable, yet the vKTx group experienced significantly fewer serious infections (11.4% vs. 32.3%, p = 0.01); the vKTx group showed a greater increase of Influenza A IgM (p = 0.05) and Influenza B IgG (p = 0.01) compared with the nvKTx group. Conclusions: Influenza vaccination prevents severe infections in KTx recipients, with good serological response and no impact on graft function or severe adverse events. Full article

Post-acute COVID-19 syndrome (PACS) is characterized by the persistence of one or more symptoms after the acute phase, leading to physical disabilities. This study aims to investigate whether the functional capacity and respiratory function 120 days post-COVID-19 differed according to the level of respiratory support needed during hospitalization in acute COVID-19 in the pre-vaccine rollout period. We followed up with 118 COVID-19 hospitalized patients in the acute phase until 120 days post-acute disease, with patients split into a Non-Invasive Oxygen Therapy Group (OTG, n = 72), Invasive Mechanical Ventilation Group (IMV, n = 12), and Room Air Group (RAG, n = 34), assessing the body composition, respiratory muscle strength, pulmonary function, functional capacity, and muscle strength at the follow-up visit. In total, 54 individuals (45.8%) were female, with a median age of 48 years old (IQR: 41–58). We found that the group with IMV was older (p < 0.001), had more admissions to the ICU (p < 0.001), and had longer hospital stays (p < 0.001). There were no statistically significant differences between groups (OTG, IMV, and RAG) for the spirometry function (p = 0.31), DASI score (p = 0.77), manovacuometry (MIP p = 0.74; MEP p = 0.23), 6MWT (p = 0.43), and handgrip (p = 0.19) outcomes. At D120, the IMV group had an important loss of body muscle mass (BMM) and a higher BMM than RAG (p = 0.02). Reduction in MIP (p = 0.01) and MEP (p = 0.02) in the IMV group and OTG group when compared to the RAG was also observed. Functional outcomes at 120 days from COVID-19 hospitalization were not found to be associated with the levels of oxygen supplementation during acute disease in this group of participants. Full article

Reverse genetics is a useful tool for studying viruses and developing vaccines for coronaviruses. However, constructing and manipulating the coronavirus genome in Escherichia coli can be time-consuming and challenging due to its large size and instability. Homologous recombination, a genetic manipulation mechanism found in organisms, is essential for DNA repair, gene recombination, and genetic engineering. In yeast, particularly Saccharomyces cerevisiae, homologous recombination technology is commonly used for constructing gene expression plasmids and genome editing. In this study, we successfully split and spliced a 30 kb viral genome fragment using yeast homologous recombination. By optimizing the program parameters, such as homologous arm lengths and fragment-to-vector ratios, we achieved a splicing efficiency of up to 97.9%. The optimal parameters selected were a 60 bp homologous sequence size and a vector fragment ratio of 1:2:2:2:2:2 for yeast homologous recombination of large DNA fragments. Full article

Background: A vaccination programme against severe acute respiratory syndrome coronavirus 2 was initiated in Portugal in December 2020. In this study, we report the findings of a prospective cohort study implemented with the objective of monitoring antibody production in response to COVID-19 vaccination. Methods: The humoral immune response to vaccination was followed up using blood samples collected from 191 healthcare workers. Participants were split into three groups: the Oxford-AstraZeneca (Vaxzevria) vaccine group (n = 68), the Pfizer-BioNTech COVID-19 (Comirnaty) vaccine group (n = 51), and the Post-COVID group (n = 72). The kinetics of anti-spike antibody production were evaluated until 56 days on average after the third dose (booster). Results: We observed that antibody titres peaked approximately one month after full vaccination and declined steadily thereafter. We also found that mRNA vaccination induces higher titres of antibodies than viral vector vaccination, and both generate greater antibody responses than mild or moderate COVID-19. Additionally, whilst the booster for the Oxford-AstraZeneca and Pfizer-BioNTech groups led to antibody levels higher than those at any previous sample collection point, the booster for the Post-COVID group (persons with a history of COVID-19 prior to vaccination) led to antibody levels lower than those attained one month after the second dose. Interpretation: Our results indicate that there are different kinetics of antibody production between individuals who received the Pfizer-BioNtech mRNA vaccine and those who received the Oxford-AstraZeneca vector vaccine, or individuals who had COVID-19 before being vaccinated. Additionally, we observed that exposure to either natural infection or vaccination modulates the response to subsequent vaccination. This is particularly evident after administration of the third dose to the Post-COVID group, where our findings point to a hindrance in vaccine boosting, probably due to unwanted feedback by high titres of pre-existing antibodies. Full article

Seasonal influenza vaccine effectiveness is low. Carbohydrate fatty acid monosulphate ester (CMS), a new oil-in-water adjuvant, has proven potency in animal models with suggested capacity for dose-sparing. The objective was to evaluate safety and immunogenicity of CMS when added to a low-dose influenza vaccine (QIV) in humans. In a randomised, double-blind, active-controlled, first-in-human study, sixty participants (18–50 years) received either 0.5 mg CMS or 2 mg CMS with 1/5th dose QIV, or a full dose QIV without CMS. Adverse events (AE) were monitored until 7 days post-vaccination. Haemagglutinin inhibition (HI) titres in serum and CD4+ T cells in PBMCs were determined at day 0, 7, 28, and 180. Mean age was 37.6 (±10.1) years and 42/60 (70.0%) were female. Pain at injection site (42/60, 86.7%) and headache (34/60, 56.7%) were reported most and more frequently in the 2 mg CMS group. HI titres and the frequency of influenza specific CD4+ T cells were equal across strains for the three cohorts on all visits, increased until day 28 and decreased at day 180 to values higher than baseline. CMS was safe in humans. Humoral and cell-mediated immunogenicity was similar across vaccines, even with 1/5th antigen dose. CMS can have beneficial implications in low-resource settings or in a pandemic context. Full article

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein–protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies. Full article

Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued research efforts, no licensed vaccine is available for protection against this disease in humans. Therefore, this study sought to develop an inactivated fragmented MERS-CoV vaccine grown in Vero cells in an hDPP4-transgenic mouse model. Two-dose immunisation in mice with 15, 20, or 25 μg of spike proteins of inactivated split MERS-CoV antigens induced neutralising antibodies, with titres ranging from NT 80 to 1280. In addition, all immunised mice were completely protected, with no virus detection in tissues, weight loss, or mortality. The immunised splenocytes produced more cytokines that stimulate immune response (IFN-γ and TNF-α) than those that regulate it (IL-4 and IL-10). Taken together, the inactivated fragmented MERS-CoV vaccine is effective for the protection of mice against lethal MERS-CoV. Thus, the inactivated fragmented MERS-CoV vaccine warrants further testing in other hosts. Full article

The influenza A(H1N1) pdm09 virus, which emerged in 2009, has been circulating seasonally since then. In this study, we conducted a comprehensive genome-based investigation to gain a detailed understanding of the genetic and evolutionary characteristics of the hemagglutinin (HA) and neuraminidase (NA) surface proteins of A/H1N1pdm09 strains circulating in Italy over a fourteen-year period from 2009 to 2023 in relation to global strains. Phylogenetic analysis revealed rapid transmission and diversification of viral variants during the early pandemic that clustered in clade 6B.1. In contrast, limited genetic diversity was observed during the 2023 season, probably due to the genetic drift, which provides the virus with a constant adaptability to the host; furthermore, all isolates were split into two main groups representing two clades, i.e., 6B.1A.5a.2a and its descendant 6B.1A.5a.2a.1. The HA gene showed a faster rate of evolution compared to the NA gene. Using FUBAR, we identified positively selected sites 41 and 177 for HA and 248, 286, and 455 for NA in 2009, as well as sites 22, 123, and 513 for HA and 339 for NA in 2023, all of which may be important sites related to the host immune response. Changes in glycosylation acquisition/loss at prominent sites, i.e., 177 in HA and 248 in NA, should be considered as a predictive tool for early warning signs of emerging pandemics, and for vaccine and drug development. Full article

Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike in vitro transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the presence of RNA-amplifying enzymes known as replicases. We recently demonstrated that this property could enhance immune responses with minimal injected RNA amounts. In saRNA-based vaccines, replicase and antigens are encoded on the same mRNA molecule, resulting in very long RNA sequences, which poses significant challenges in production, delivery, and stability. In taRNA-based vaccines, these challenges can be overcome by splitting the replication system into two parts: one that encodes replicase and the other that encodes a short antigen-encoding RNA called transreplicon. Here, we review the identification and use of transreplicon RNA in alphavirus research, with a focus on the development of novel taRNA technology as a state-of-the art vaccine platform. Additionally, we discuss remaining challenges essential to the clinical application and highlight the potential benefits related to the unique properties of this future vaccine platform. Full article

Background and Objectives: We aimed to explore whether the COVID-19 pandemic influenced hospitalizations for ambulatory care-sensitive conditions (ACSCs) in Split-Dalmatia County, Croatia. Materials and Methods: We performed a cross-sectional comparative study using two different time periods, the pre-pandemic (from March 2019 to February 2020) and the pandemic period (from March 2020 to February 2021), to explore the possible influences that the COVID-19 pandemic had on hospitalizations for ACSCs. The ACSCs were classified into the categories of vaccine-preventable, chronic, and acute disease. The indicators were statistically analyzed. Results: During the pandemic, a decrease in the total number of hospitalizations and ACSC hospitalizations was recorded. The relative risk for having any ACSC hospitalization in the pandemic period compared to the pre-pandemic period was 0.67 (95% CI, 0.64–0.71; p = 0). The risk reduction was seen in all three categories of vaccine-preventable ACSCs, chronic disease, and acute disease. Large reductions were found in the relative risk of hospitalization for COPD and asthma. Considering the mode of discharge, there was a statistically significantly higher risk of ACSCs with fatal outcomes during the pandemic than in the pre-pandemic period (relative risk 1.31; 95% CI, 1.01–1.7; p = 0.0197). Conclusions: The results of this study show that the COVID-19 pandemic influenced the total number of hospitalizations as well as hospitalizations relating to ACSCs. Certainly, one of the reasons for these changes was due to organizational changes in the working of the entire health system due to the COVID-19 pandemic. Full article

This study explored the optimum immunization schedule for the quadrivalent influenza split-virion vaccine containing influenza A strains (H1N1 and H3N2) and B lineage strains (Yamagata and Victoria) in children aged 3–8 years. The 652 participants enrolled were divided into two groups based on a history of influenza immunization (IH group) or no history of influenza immunization (NH group). The groups were administered a two-dose immunization schedule on days 0 and 30. In the NH group, on day 30 after the first dose, the positive rates of influenza hemagglutination-inhibition antibodies of strains H1N1, H3N2, BV, and BY were 85.85%, 71.70%, 65.27% and 60.45%, respectively. The positive rates of BV and BY failed to meet the absolute criteria for evaluating the immunogenicity of influenza vaccine in the population aged 3–60 years (for each strain antibody). On day 30 after the second dose, HI antibodies to strains H1N1, H3N2, BV, and BY met the immunogenicity acceptable criteria. In the IH group, on day 30 after the first dose, HI antibodies to strains H1N1, H3N2, BV, and BY met the acceptable criteria for immunogenicity. The incidence rates of adverse reactions (vaccine-related adverse events) from the first dose up until 30 days after the second dose were 20.80% in the IH group and 19.50% in the NH group. Only two Grade 3 adverse reactions (fever: temperature ≥ 39.5 °C, swelling: area ≥ 50% of the injection site area) occurred in the IH group, and no Grade 3 adverse reactions occurred in the NH group. No serious adverse reactions occurred in either group. We conclude that for the NH group, two doses of quadrivalent influenza vaccine should be administered, and for the IH group, a one-dose regimen is acceptable. Full article