Vaccines

Emerging numbers of SARS-CoV-2 infections are currently combated with a third vaccination. Considering the different vaccination regimens used for the first two vaccine doses, we addressed whether the previous vaccination influences the immune response to the booster. Participants for this prospective study were recruited from among healthcare workers. N = 20 participants were previously vaccinated with two doses of BNT162b2, and n = 53 received a priming dose of ChAdOx1-nCoV-19 followed by a BNT162b2 dose. Participants were vaccinated with a third dose of BNT162b2 in December 2021. Antibody concentrations were determined after vaccination, and in a subset of n = 19 participants, T cell responses were evaluated. Anti-S concentrations and IFNγ production increased during the first 21 days. The choice of the first and second vaccineshad no influence on the final outcome of the booster vaccination. Before booster vaccination, antibody concentrations were lower for older participants but increased more strongly over time. Full article

Recently, long synthetic peptides or in silico-predicted epitope peptides have been used to identify T cell epitopes, but these approaches may not be suitable for investigating naturally processed epitopes. Here, mRNAs, including fragments or predicted epitope sequences of HCMV pp65 antigen, were generated by in vitro transcription following transcriptionally active PCR. Then, artificial antigen-presenting cells (aAPCs) expressing a single HLA allotype were transfected with mRNAs to identify epitopes in donors with T cell responses that recognize pp65 antigen restricted to HLA-A*02:01, -A*02:06, or -B*07:02. T cells restricted to a particular HLA allotype showed positive responses in some of the 10 fragment antigens. Among predicted epitopes within these positive fragments, three epitopes of HLA-A*02:01, -A*02:06, and -B*07:02 were confirmed. In addition, T cells expanded by anti-CD3 stimulation for two weeks could also be effectively used for the identification of these T cell epitopes, although there were individual differences. These results demonstrated that fragment antigens and epitopes can be rapidly generated using mRNA, and naturally processed antigenic regions can be detected using aAPCs without a T cell cloning procedure. This method will help to identify novel T cell epitopes for developing immunotherapy and vaccines against infectious diseases and cancer. Full article

Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. In this study, we generated a chimeric VLP-based COVID-19 vaccine stably produced by HEK293T cells. The chimeric VLPs contain the influenza virus A matrix (M1) proteins and the SARS-CoV-2 Wuhan strain spike (S) proteins with a deletion of the polybasic furin cleavage motif and a replacement of the transmembrane and cytoplasmic tail with that of the influenza virus hemagglutinin (HA). These resulting chimeric S-M1 VLPs, displaying S and M1, were observed to be enveloped particles that are heterogeneous in shape and size. The intramuscular vaccination of BALB/c mice in a prime-boost regimen elicited high titers of S-specific IgG and neutralizing antibodies. After immunization and a challenge with SARS-CoV-2 in K18-hACE2 mice, the S-M1 VLP vaccination resulted in a drastic reduction in viremia, as well as a decreased viral load in the lungs and improved survival rates compared to the control mice. Balanced Th1 and Th2 responses of activated S-specific T-cells were observed. Moderate degrees of inflammation and viral RNA in the lungs and brains were observed in the vaccinated group; however, brain lesion scores were less than in the PBS control. Overall, we demonstrate the immunogenicity of a chimeric VLP-based COVID-19 vaccine which confers strong protection against SARS-CoV-2 viremia in mice. Full article

Despite the substantial efforts at ensuring universal access to routine immunisation services among children in South Africa, major gaps in immunisation coverage remain. This study assessed the magnitude of missed opportunities for vaccination (MOV) and associated factors among children aged 0–23 months attending primary health care (PHC) facilities in Cape Town. We used multilevel binomial logistic regression models to explore individual and contextual factors associated with MOV, with children aged 0–23 months at Level 1, nested within PHC facilities (Level 2). A total of 674 children and their caregivers were enrolled. MOV prevalence was 14.1%, ranging from 9.1% to 18.9% across sub-districts. Dose-specific MOV prevalence was highest for the second dose of measles vaccine (9.5%) and lowest for the first dose of rotavirus vaccine (0.6%). The likelihood of a child experiencing MOV was significantly associated with caregivers’ low level of education (Odds ratio (OR) = 3.53, 95% credible interval (CrI): 1.13–11.03), recent receipt of immunisation messages (OR = 0.46, 95%CrI: 0.25–0.87), shared immunisation decision making by both parents (OR = 0.21, 95%CrI: 0.07–0.62) and health facility staff number (OR = 0.18, 95%CrI: 0.06–0.61). The burden of MOV among children in Cape Town is influenced by individual and contextual factors, which provide important opportunities for quality improvement and broader strategies to improve routine immunisation service delivery. Full article

To identify factors that influenced Moroccans’ intention to get a COVID-19 vaccine, a cross-sectional survey among a Moroccan sample was conducted based on Health Belief Model constructs. Participants’ sociodemographic characteristics, perceived susceptibility, perceived severity, perceived barriers, perceived benefits, self-efficacy, cues to action, and intention to receive vaccine data were collected and analyzed using a structural equation model (SEM). The survey was completed by 3800 individuals; 57.2% were men, 44.5% were aged 30 to 44, and 44.6% were married. After controlling for confounders, being a woman and having a chronic disease were associated with higher acceptance of the COVID-19 vaccine. The strongest predictor for the intention of receiving a vaccine was participants who were married. Most of the HBM constructs were shown to be significantly associated with vaccine acceptance. Susceptibility and Benefits were the strongest predictors of acceptance of the COVID-19 vaccine (standardized path coefficient, SPC = 0.23), followed by Severity (SPC = 0.22). Conversely, given the negative correlation between barriers and intention (SPC = −0.08), it is necessary to maintain a high level of transparency regarding the vaccines’ safety. Our study provides guidance for an implementation of vaccination strategies, intending to bolster the overall COVID-19 immunization program. Full article

COVID-19 vaccination is considered the most effective and promising approach for the elimination of the SARS-CoV-2 pandemic globally. Although the vaccine has been proven to be safe, as evidenced by the promotion of mass vaccination, new side effects, including several ocular complications that were not described during the experimental stage, are now emerging. In the present study, we report a 33-year-old Chinese man who developed probable Vogt–Koyanagi–Harada (VKH) disease only one day after his first dose of an inactivated COVID-19 vaccine, without any systemic symptoms. His medical history was unremarkable, except for hypertension. Although successfully relieved by oral prednisone, the patient progressed to the chronic stage of VKH disease with ocular depigmentation 4 months after onset. By reviewing similar cases previously reported, we discuss and summarize the common characteristics of VKH disease associated with vaccines against SARS-CoV-2, as well as the possible mechanisms behind this phenomenon. Although the causality is unclear, ophthalmologists and generalists should be aware of this possible ocular adverse effect after COVID-19 vaccination. Full article

Infectious laryngotracheitis (ILT) is caused by Gallid herpesvirus-1 (GaHV-1) or infectious laryngotracheitis virus (ILTV) and was first described in Canadian poultry flocks. In Canada, ILTV infection is endemic in backyard flocks, and commercial poultry encounters ILT outbreaks sporadically. A common practice to control ILT is the use of live attenuated vaccines. However, outbreaks still occur in poultry flocks globally due to ILTV vaccine strains reverting to virulence and emergence of new ILTV strains due to recombination in addition to circulating wildtype strains. Recent studies reported that most of the ILT outbreaks in Canada were induced by the chicken-embryo-origin (CEO) live attenuated vaccine revertant strains with the involvement of a small percentage of wildtype ILTV. It is not known if the host responses induced by these two ILTV strains are different. The objective of the study was to compare the host responses elicited by CEO revertant and wildtype ILTV strains in chickens. We infected 3-week-old specific pathogen-free chickens with the two types of ILTV isolates and subsequently evaluated the severity of clinical and pathological manifestations, in addition to host responses. We observed that both of the isolates show high pathogenicity by inducing several clinical and pathological manifestations. A significant recruitment of immune cells at both 3 and 7 days post-infection (dpi) was observed in the tracheal mucosa and the lung tissues of the infected chickens with wildtype and CEO vaccine revertant ILTV isolates when compared to uninfected controls. Overall, this study provides a better understanding of the mechanism of host responses against ILTV infection. Full article

The infections and deaths resulting from Coronavirus Disease 2019 (COVID-19) triggered the need for some governments to make COVID-19 vaccines mandatory. The present study aims to analyze the position of 3026 adults in Colombia, El Salvador, and Spain regarding the possibility of making COVID-19 vaccine mandatory and the intention to be vaccinated with the booster or possible successive doses. Data from an online survey conducted from August to December 2021 among a non-representative sample of Spanish-speaking countries were collected. Multinomial Logistic Regression Models were used. A total of 77.4% of Colombians were in favor of mandatory vaccination compared to 71.5% of Salvadorians and 65.4% of Spaniards (p < 0.000). Women and people over 65 years of age were the groups most in favor of making the vaccine mandatory (p < 0.000). A total of 79.4% said they had received a third dose or would intend to receive the third dose or future doses, if necessary, compared with 9.4% who expressed doubts and 9.9% who refused to be vaccinated or did not intend to be vaccinated. Among the measures that could be taken to motivate vaccination, 63.0% and 60.6% were in favor of requiring a negative test to enter any place of leisure or work, respectively, compared to 16.2% in favor of suspension from work without pay. The acceptance of mandatory vaccination and of third or future doses varies greatly according to sociodemographic characteristics and work environment. As such, it is recommended that policy makers adapt public health strategies accordingly. Full article

Vaccination saves lives and can be an effective strategy for preventing the spread of the COVID-19, but negative attitudes towards vaccines lead to vaccine hesitancy. This study aimed to explore the factors influencing the uptake of the COVID-19 vaccine in the Nepali community in the United Kingdom (UK). This qualitative study included in-depth interviews with 20 people from Nepal living in the UK. Interviews were conducted by a native-Nepali speaker and all interviews were audio-recorded, transcribed, and translated into English before being analysed thematically. Our study found that attitudes towards COVID-19 are generally positive. Nine overlapping themes around barriers to COVID-19 vaccination were identified: (a) rumours and mis/disinformation; (b) prefer home remedies and yoga; (c) religion restriction; (d) concern towards vaccine eligibility; (e) difficulty with online vaccine booking system; (f) doubts of vaccine effectiveness after changing the second dose timeline; (g) lack of confidence in the vaccine; (h) past bad experience with the influenza vaccine; and (i) worried about side-effects. Understanding barriers to the uptake of the COVID-19 vaccine can help in the design of better targeted interventions. Public health messages including favourable policy should be tailored to address those barriers and make this vaccination programme more viable and acceptable to the ethnic minority communities in the UK. Full article

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case–control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June–September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June–July (delta variant proportion 45%) was 92% and 79% in the period August–September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants. Full article

Here, we evaluated over time in different cohorts of children vaccinated against serogroup C Neisseria meningitidis, the presence of antibodies with neutralizing activity. A total of 348 sera samples of enrolled children by year since vaccination (<1 year- up to 5 years), starting from February 2016 to December 2017, were collected in three collaborating centers. Meningococcal serogroup C (MenC) antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA) following standard operating procedures. The cut-off of rSBA titer ≥ 8 is considered the correlate of protection. We observed a significantly declining of bactericidal rSBA titers by 23% every year, for every 1-year from vaccination (Adjusted PR = 0.77, 95% CI: 0.71–0.84). The proportions of children with bactericidal antibodies, immunized with the meningococcal serogroup C conjugate (MCC) vaccine, declined from 67.7% (95% CI: 48.6–83.3%) one year after vaccination, to 36.7% (95% CI: 19.9–56.1%) five years after vaccination (chi-square for linear trend, p < 0.001). Children vaccinated with the tetravalent meningococcal serogroup ACWY vaccine resulted in a high proportion of bactericidal rSBA MenC titer ≥ 1:8 (90.6%, 95% CI: 79.3–96.9%) after a mean time of seven months. Overall, the results provide some evidences on the evaluation of meningococcal serogroup C bactericidal antibodies after primary vaccination. Full article

The objectives of the survey were to explore any changes in the adherence to the three main COVID-19 preventive measures (social distancing, washing hands, wearing face-masks) among 795 individuals who received the COVID-19 vaccine booster dose in Italy and to identify the predictors associated. The concern of contracting COVID-19 before the vaccination, after the primary COVID-19 vaccine series, and after the booster dose resulted with a mean value of 7.7, 4.6, and 4.2, respectively. Females, those who had a lower mean self-perceived health status, who perceived COVID-19 as a very serious health problem, who decided to receive the booster dose because they perceived to be at risk of getting COVID-19, and who expressed interest in acquiring more information regarding the COVID-19 vaccine booster dose were more likely to report a higher concern of contracting COVID-19 after the booster dose. Over two-thirds were willing to respect the three main COVID-19 preventive measures following the booster dose. The multinomial logistic regression analysis showed that those who had used all three main preventive measures before and after the second or single dose were less likely to perceive COVID-19 as a serious illness. Those who had used them irregularly were less likely to have used official government organizations and scientific journals as sources of information. This survey provided an understanding regarding the adherence to COVID-19 preventive measures that may help to target policy interventions needed to reduce the spread of SARS-CoV-2. Full article

Background: Hyperglycemia can alter the activation of innate and acquired immunity, but epidemiological evidence linking hyperglycemia to post-vaccination immunogenicity is limited. Objective: To examine the association between SARS-CoV-2 spike antibody titers after the COVID-19 vaccine and impaired fasting glucose (IFG) and diabetes. Methods: Participants were 953 health care workers aged 21–75 years who were tested for SARS-CoV-2 spike IgG antibodies and underwent a health checkup two months after their second dose of the BNT162b2 vaccine. IFG was defined as a fasting plasma glucose (FPG) level of 100–125 mg/dL, and diabetes was defined as an FPG level ≥ 126 mg/dL or being under medical care for diabetes. Multivariable linear regression was used to calculate the ratio of the mean. Result: Spike IgG antibody titers were lower in the presence of hyperglycemia; the ratios of the means (95% CI) were 1.00, 0.79 (0.60–1.04), and 0.60 (0.42–0.87) for individuals with normoglycemia, IFG, and diabetes, respectively (p trend < 0.001). Restricted cubic spline regression analysis showed that IgG spike antibody titers decreased linearly with increasing concentrations of FPG. Conclusion: Diabetes and, to a lesser extent, IFG may be associated with poor humoral immune response after BNT162b2 vaccination. Full article

In the vaccine industry, multiple physicochemical, immunological, in vitro and in vivo analytical methods are applied throughout the manufacturing process to characterize and monitor the quality of vaccines. Presented here is the Single Epitope Antigenicity Test (SEAT), an innovative, quantitative epitope profiling method which provides an extended immunochemical analysis for diphtheria toxoid (DTxd) to be used for consistency testing during manufacturing process changes. The method uses BioLayer Interferometry (BLI) and a panel of monoclonal antibodies (mAbs) to independently assess nine individual antigenic sites of DTxd. The panel includes mAbs which are functional, bind distinct sites on DTxd and are able to distinguish intact DTxd from that which has been exposed to heat treatment. The SEAT method was qualified for precision, accuracy, and linearity, and was used to define a preliminary comparability range for DTxd made using the current manufacturing process. DTxd lots manufactured using alternate processes were assessed in the context of this range to determine the impact on DTxd antigenicity. Epitope profiling by SEAT provides quantitative information on the integrity of multiple important antigenic regions of DTxd, and therefore represents a valuable tool in a comprehensive analytical test package which can be used to support manufacturing process changes for vaccines. Full article

Background: in 2020, a new form of coronavirus spread around the world starting from China. The older people were the population most affected by the virus worldwide, in particular in Italy where more than 90% of deaths were people over 65 years. In these people, the definition of the cause of death is tricky due to the presence of numerous comorbidities. Objective: to determine whether COVID-19 was the cause of death in a series of older adults residents of nursing care homes. Methods: 41 autopsies were performed from May to June 2020. External examination, swabs, and macroscopic and microscopic examination were performed. Results: the case series consisted of nursing home guests; 15 men and 26 women, with a mean age of 87 years. The average number of comorbidities was 4. Based only on the autopsy results, the defined cause of death was acute respiratory failure due to diffuse alveolar damage (8%) or (31%) bronchopneumonia with one or more positive swabs for SARS-CoV-2. Acute cardiac failure with one or more positive swabs for SARS-CoV-2 was indicated as the cause of death in in symptomatic (37%) and asymptomatic (10%) patients. Few patients died for septic shock (three cases), malignant neoplastic diseases (two cases), and massive digestive bleeding (one case). Conclusions: Data from post-mortem investigation were integrated with previously generated Geriatric Index of Comorbidity (GIC), resulting in four different degrees of probabilities: high (12%), intermediate (10%), low (59%), and none (19%), which define the level of strength of causation and the role of COVID-19 disease in determining death. Full article

Having been affected by the highest increase in COVID-19 cases since the start of the pandemic, Honolulu and Maui counties in Hawaii implemented vaccine passport mandates for select industries in September 2021. However, the degree to which such mandates impacted COVID-19 mitigation efforts and economics remains poorly understood. Herein, we describe the effects of these mandates on changes in three areas using difference-in-difference regression models: (1) business foot traffic; (2) number of COVID-19 cases per 100,000 individuals, and (3) COVID-19 vaccination rates across counties affected or unaffected by the mandates. We observed that although businesses affected by mandates experienced a 6.7% decrease in foot traffic over the 14 weeks after the mandates were implemented, the number of COVID-19 cases decreased by 19.0%. Notably, the vaccination rate increased by 1.41% in counties that implemented mandates. In addition, towards the end of the studied period, the level of foot traffic at impacted businesses converged towards the level of that of non-impacted businesses. As such, the trade-off in temporary losses at businesses was met with significant gains in public health and safety. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, the current mAbs produced in mammalian cells are expensive and might be unaffordable for many. Furthermore, the emergence of variants of concern demands the development of strategies to prevent mutant escape from mAb treatment. Using a cocktail of mAbs that bind to complementary neutralizing epitopes is one such strategy. In this study, we use Nicotiana benthamiana plants in an effort to expedite the development of efficacious and affordable antibody cocktails against SARS-CoV-2. We show that two mAbs can be highly expressed in plants and are correctly assembled into IgG molecules. Moreover, they retain target epitope recognition and, more importantly, neutralize multiple SARS-CoV-2 variants. We also show that one plant-made mAb has neutralizing synergy with other mAbs that we developed in hybridomas. This is the first report of a plant-made mAb to be assessed as a potential component of a SARS-CoV-2 neutralizing cocktail. This work may offer a strategy for using plants to quickly develop mAb cocktail-based therapeutics against emerging viral diseases with high efficacy and low costs. Full article

Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (CDK1, EGFR, FYN, UBC, MYC, CCNB1, FOS, RHOB, CDC6, CDC20, and CHEK1) as the hub-DEGs (potential key genes) by the protein–protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (FOXC1, GATA2, YY1, and NFIC) and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatment. Full article

Enteroviruses have now been shown to persist in cell cultures and in vivo by a novel mechanism involving the deletion of varying amounts of the 5′ terminal genomic region termed domain I (also known as the cloverleaf). Molecular clones of coxsackievirus B3 (CVB3) genomes with 5′ terminal deletions (TD) of varying length allow the study of these mutant populations, which are able to replicate in the complete absence of wildtype virus genomes. The study of TD enteroviruses has revealed numerous significant differences from canonical enteroviral biology. The deletions appear and become the dominant population when an enterovirus replicates in quiescent cell populations, but can also occur if one of the cis-acting replication elements of the genome (CRE-2C) is artificially mutated in the element’s stem and loop structures. This review discusses how the TD genomes arise, how they interact with the host, and their effects on host biology. Full article