Vaccines, Volume 10, Issue 12 (December 2022) – 205 articles

Long-term care facilities (LTCFs) were severely affected by COVID-19, in particular in Northern Italy. We aimed to assess antibody responses among residents and healthcare workers (HCWs) of 13 LTCFs through serum samples collected at three time points: prior to, two weeks, and 9 months after receiving Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine (respectively t0, t1, and t2). IgG antibodies targeted towards the S1 domain of the spike protein were measured, and results were expressed in binding antibody units (BAU/mL). Friedman’s average rank test was performed to compare antibody titres between the three time points. Two logistic regression models were built to identify independent predictors of (1) developing and (2) maintaining a significant antibody response to vaccination, using a previously identified threshold. In total, 534 subjects were enrolled (371 HCWs and 163 residents). The antibody titres at t1 were the highest; at t2, the IgG titres significantly decreased, remaining however 10 times higher compared to titres at t0. Previous infection was the only significant predictor of developing and maintaining a response over threshold in both models. Results of this study provided further insights on the humoral response elicited by vaccination, and on host factors determining variations in its magnitude and kinetics. Full article

Prone positioning (PP) improves oxygenation and survival in patients with severe acute respiratory distress syndrome (ARDS). Data regarding feasibility and effectiveness of PP in pregnancy are lacking. This subgroup analysis of a cohort study that included mechanically ventilated pregnant women presenting with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ARDS who underwent PP aims to assess the efficacy and safety of PP. Ventilatory and gasometric parameters were evaluated at baseline (T₀) and in prone (T₁) and supine (T₂) positions. Obstetric outcomes were also assessed. Sixteen cases at an average of 27.0 (22.0–31.1) gestational weeks of pregnancy were included. Obesity and hypertension were frequent comorbidities. PP was associated with a >20% increase in PaO₂ levels and in PaO₂/FiO₂ ratios in 50% and 100% of cases, respectively. The PaO₂/FiO₂ ratio increased 76.7% (20.5–292.4%) at T₁ and 76.9% (0–182.7%) at T₂. PP produced sustained improvements in mean PaO₂/FiO₂ ratio (p < 0.001) and PaCO₂ level (p = 0.028). There were no cases of emergency delivery or suspected fetal distress in pregnancies ≥25 weeks during the 24 h period following PP. PP is safe and feasible during pregnancy, improving PaO₂/FiO₂ ratios and helping to delay preterm delivery in severe ARDS. Full article

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease in cloven-hoofed animals. To prevent the spread of FMD virus (FMDV), traditional inactivated vaccines are used to immunize susceptible animals in disease-endemic countries. However, the inactivated FMD vaccine has several limitations, including safety concerns. To overcome these limitations, subunit proteins have been studied as alternative vaccine candidates. In this study, we designed two multiepitope recombinant proteins (OVM and AVM) containing antigenic sites (residue of VP1 132–162 and residue of VP1 192–212) of three topotypes of FMDV serotype O or three topotypes of FMDV serotype A. Each recombinant protein was efficiently expressed in Escherichia coli with high solubility, and the immunogenicity and protective efficacy of the proteins as FMD vaccine candidates were evaluated. The results showed that OVM and AVM emulsified with ISA201 adjuvant induced effective antigen-specific humoral and cell-mediated immune responses and successfully protected mice from O/Jincheon/SKR/2014, O/VET/2013, and A/Malaysia/97 viruses. In addition, intramuscular immunization of pigs with the OVM and AVM emulsified with ISA201 elicited effective levels of neutralizing antibodies to the viruses with homologous epitopes. Importantly, OVM-AVM emulsified with CAvant^®SOE-X adjuvant conferred 100% protection against the O/Jincheon/SKR/2014 virus with homologous residues and 75% protection against A/SKR/GP/2018 with heterologous residues. The results presented in this study suggest that the combination of OVM and AVM protein with an effective adjuvant could yield an effective and safe vaccine candidate for the prevention and control of foot-and-mouth disease. In addition, our results provide a vaccine platform that can safely, cost-efficiently, and rapidly generate protective vaccine candidates against diverse FMDVs. Full article

Vaccine effectiveness (VE) and the urgency of booster vaccination against SARS-CoV-2 Omicron variant need evaluation. A systematic search was conducted from 1–6 April, 2022. VE difference (VED) estimates were assessed using random-effects and meta-regression analyses were performed for evaluating VE over time. Compared to full dose, booster dose of overall vaccines provided better protection against any and severe Omicron infections within 3 months (p < 0.001), and within 3 months or more in any, severe, and symptomatic infections (p < 0.001). From meta-regression analysis of overall vaccines, the full-dose VE against any and symptomatic Omicron infections reduced per month by 2.45% and 5.5%, respectively; whereas booster dose effectiveness against any and symptomatic Omicron infections reduced per month by 1.79% and 1.14%, respectively. The VE estimates of booster dose provide excellent protection against symptomatic infection compared to full dose. The VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 against Omicron infection are generally moderate, despite the VE estimates declining over time. Full article

Background: Outbreaks of small ruminant morbillivirus (SRMV) are regularly occurring in Pakistan despite vaccine availability. This study was designed to identify substitutions within the immunogenic structural and functional regions of the nucleocapsid, fusion, and hemagglutinin genes of SRMV and their comparison with vaccinal strains of Nigerian and Indian origin. Methods: Swabs and tissue samples were collected from diseased animals. RT-PCR was used to characterize selected genes encoded by viral RNA. The study’s N, F, and H protein sequences and vaccinal strains were analyzed for B and T cell epitope prediction using ABCpred, Bipred, and IEDB, respectively. Results: Significant substitutions were found on the C terminus of the nucleocapsid, within the fusion motif region of the fusion gene and in the immunoreactive region of the hemagglutinin gene. Conclusion: Our results emphasize the need for the development of effective vaccines that match the existing variants of SRMV strains circulating in Pakistan. Full article

Low pathogenic avian influenza (LPAI) H9N2 virus is one of the major poultry pathogens associated with severe economic losses in the poultry industry (broiler, layers, breeders, and grandparents’ flocks), especially in endemic regions including the Middle East, North Africa, and Asian countries. This work is an attempt to evaluate the efficacy of whole inactivated H9N2 vaccine (MEFLUVAC^TM H9) in turkey poults kept under laboratory and commercial farm conditions. Here, 10,000 white turkey poults (1-day old) free from maternally derived immunity against H9N2 virus were divided into four groups; G1 involved 10 vaccinated birds kept under biosafety level-3 (BLS-3) as a laboratory vaccinated and challenged group, while G2 had 9970 vaccinated turkeys raised on a commercial farm. Ten of those birds were moved to BLS-3 for daily cloacal and tracheal swabbing to check for the absence of any life-threating disease, before conducting analyses. G3 (10 birds) served as a non-vaccinated challenged control under BSL-3 conditions, while G4 (10 birds) was used as a non-vaccinated and non-challenged control under BSL-3 conditions. Sera were collected on days 7-, 14-, 21-, and 28-post-vaccinations to monitor the humoral immune response using a hemagglutination-inhibition (HI) test. At these same intervals, cloacal and tracheal swabs were also checked for any viral infection. The challenge was conducted 28 days post-vaccination (PV) using AI-H9N2 in BSL-3 by intranasal inoculation of 6-log10 embryo infective dose₅₀ (EID₅₀). At 3-, 6-, and 10-days post-challenge, oropharyngeal swabs were taken from challenged birds to quantify viral shedding by quantitative polymerase chain reaction (qRT-PCR). The results of this study showed that vaccinated groups (G1/2) developed HI titers of 1.38, 4.38, 5.88, and 7.25 log₂ in G1 vs. 1.2, 3.8, 4.9 and 6.2 log₂ in G2 when measured at 7-, 14-, 21- and 28-days PV, respectively, while undetectable levels were recorded in non-vaccinated groups (G3/4). Birds in G3 showed 90% clinical sickness vs. 10% and 20% in G1/2, respectively, over a 10-day monitoring period following challenge. Vaccinated birds showed a significant reduction in virus shedding in terms of the number of shedders, amount of shed virus and shedding interval over the non-vaccinated challenged birds. Regarding mortality, all groups did not show any mortality, which confirms that the circulating H9N2 virus still has low pathogenicity and cannot cause mortality. However, the virus may cause up to 90% clinical sickness in non-vaccinated birds vs. 10% and 20% in laboratory- and farm-vaccinated birds, respectively, highlighting the role of the vaccine in limiting clinical sickness cases. In conclusion, under the current trial circumstances, MEFLUVAC^TM-H9 provided protective seroconversion titers, significant clinical sickness protection and significant reduction in virus shedding either in laboratory- or farm-vaccinated groups after a single vaccine dose. Full article

Data for predicting the severity and mortality of coronavirus disease 2019 (COVID-19) are limited, and investigations are ongoing. Endothelial monocyte-activating protein II (EMAP-II) is a multifunctional polypeptide with pro-inflammatory properties. EMAP-II is a significant pathogenic component in chronic inflammatory lung diseases and lung injury. In this study, we aimed to assess the potential utility of EMAP-II as a predictor of COVID-19 severity and mortality. This study included 20 healthy volunteers and 60 verified COVID-19 patients. Nasopharyngeal samples from COVID-19-positive subjects and normal volunteers were collected at admission. The nasopharyngeal samples were subjected to EMAP-II real-time polymerase chain reaction (RT-PCR). EMAP-II RNA was not detected in nasopharyngeal swabs of normal controls and mild to asymptomatic COVID-19 patients and was only detectable in severe COVID-19 patients. EMAP-II critical threshold (Ct) was positively associated with lymphocyte percentages and oxygen saturation (p < 0.001) while being negatively associated with age (p = 0.041), serum CRP, ferritin, and D-dimer levels (p < 0.001). EMAP-II Ct cutoff ≤34 predicted a worse outcome in COVID-19 illness, with a sensitivity and specificity of 100%. Our study suggests that EMAP-II could be considered a potential biomarker of COVID-19 severity. EMAP-II can predict the fatal outcome in COVID-19 patients. Full article

Data on immunogenicity of adenovirus-vectored vaccine in chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, we aimed to determine the humoral and cellular immune responses after homologous ChAdOx-1 vaccination in subjects with COPD. COPD subjects and age- and sex-matched healthy elderly receiving ChAdOx-1 homologous vaccination were included. The levels of neutralizing antibodies (NAb) and specific CD4 and CD8 T-cell responses against SARS-CoV-2 wild-type (WT) and variants of concern (VOCs: Alpha, Beta, Delta, and Omicron) were measured. Eight COPD patients were matched with eight control participants. After vaccination for 4 and 12 weeks, % inhibition of NAb against Alpha, Beta, and Delta in both groups were comparable and significantly higher than baseline. The percentage inhibition of NAb at the 12th week was significantly dropped from the 4th week in each group. The NAb against the Omicron variant, however, were much lower than Alpha, Beta, Delta variants. The increasing trend in the number of CD4 T-cells producing TNF-α, IFN-γ, IL-10, and FasL upon stimulation with spike peptides of WT and VOCs was observed in COPD patients compared to the healthy group. These responses were not observed in CD8 T-cells. Homologous ChAdOx-1 vaccination could induce comparable NAb against the SARS-CoV-2 WT, Alpha, Beta, Delta, and Omicron variants between COPD and healthy elderly. The CD4 T-cell responses did not differ between COPD patients and healthy control. Full article

Porcine circovirus type 2 (PCV2) is a highly prevalent virus in pig farms worldwide that causes significant economic losses in the swine industry. The PCV2 virus-like particles (VLPs) are potent subunit vaccines that are widely used. Currently, the adopted quality control of VLPs vaccines is mainly based in animal testing, the titration of neutralizing antibodies, or other biochemical/biophysical assays. In this study, we generated a monoclonal antibody that can distinguish assembled PCV2 VLPs from the capsid proteins. Subsequently, a convenient Sandwich ELISA was developed based on the monoclonal antibody (mAb) that recognizes the PCV2 VLPs specifically. This assay can be used for the quantity and quality control of PCV2 VLPs vaccines for both the intermediate or final products with high accuracy. Full article

Although neurological complications after the administration of vaccines against coronavirus disease 2019 (COVID-19) are rare, they might result in long-term morbidity. This study was designed to determine the risk of peripheral nervous system (PNS) adverse events after the administration of mRNA vaccines against COVID-19. Large-scale randomized controlled trials (RCTs) and cohort studies were systematically searched in databases, and 15 cohort studies were included in the synthesis. Among all PNS adverse events, only Bell’s palsy and Guillain–Barré syndrome (GBS) had sufficient data and were included for further analysis. Individuals who received mRNA vaccines had a higher risk of Bell’s palsy than the unvaccinated group, and the risk of Bell’s palsy after BNT162b2 was significantly higher than after mRNA-1273. Regarding GBS, no significant difference in the risk was observed between BNT162b2 and the unvaccinated group, but BNT126b2 introduced a higher risk of post-vaccinated GBS than mRNA-1273. In conclusion, PNS adverse events, especially Bell’s palsy, should be carefully observed after mRNA vaccination against COVID-19. With the opportunity of vaccination campaigns on such a large scale, further investigation and surveillance of post-vaccination neurological adverse events should also be established. Full article

Since the global COVID-19 pandemic has great impact on human health and life style, the vaccination is the most effective method for disease control and prevention. However, not all people are willing to be vaccinated because some critical factors affect vaccination aspiration and vaccine choice of the public population. Among these factors, public mental health belongs to a political issue. In this study, Google Trend Search was used to explore the correlation between COVID-19 vaccination choice and public mental health during the period from August/2020 to December/2021. The results suggested that the main public concerns of COVID-19-related mental illnesses are positively correlated with the new cases amount but are negatively correlated with total cases and vaccinated cases amount. Moreover, the results support that the public population took more interest in the Pfizer/BNT COVID vaccine and Moderna COVID vaccine than the AstraZeneca COVID vaccine. Our study shows that investigations of the public mental health should be set up and conducted widely. A complete vaccination program combined with a policy for the improvement of public mental health are very effective for the control and prevention of COVID-19. Full article

This study compares the clinical characteristics and disease progression among vaccinated and unvaccinated pregnant and postpartum women who tested positive for different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the Brazilian epidemiological data. Data of pregnant or postpartum patients testing positive for SARS-CoV-2 and presenting with coronavirus disease 2019 (COVID-19) from February 2020 to July 2022 were extracted from Brazilian national database. The patients were grouped based on vaccination status and viral variant (original, Gamma, Delta, and Omicron variants), and their demographics, clinical characteristics, comorbidities, symptoms, and outcomes were compared retrospectively. Data of 10,003 pregnant and 2361 postpartum women were extracted from the database. For unvaccinated postpartum women, intensive care unit (ICU) admission was more likely; invasive ventilation need was more probable if they tested positive for the original, Gamma, and Omicron variants; and chances of death were higher when infected with the original and Gamma variants than when infected with other variants. Vaccinated patients had reduced adverse outcome probability, including ICU admission, invasive ventilation requirement, and death. Postpartum women showed worse outcomes, particularly when unvaccinated, than pregnant women. Hence, vaccination of pregnant and postpartum women should be given top priority. Full article

A vaccine is a type of medicine that increases immunity and the number of antibodies (IgM and IgG) when injected into the body, preparing it in case of an actual viral infection. It has been shown in several studies that there is a significant relationship between physical activity and vaccination. Furthermore, it has been documented that physical activity can play a major role in reducing stress. Evidence also shows the existence of a relationship between immunity, vaccine response, and sleep duration. To investigate the effects of physical activity on the level of COVID-19 antibodies and lifestyle-related factors, Health Science Center (HSC) students who had taken the third dose of the vaccine and had no prior infection of the COVID-19 virus were investigated. To serve the purpose of this study, an anti-SARS-CoV-2 test was applied by taking a blood sample from the students. The Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires and the Borg’s 15-point scale were given to the participants to fill out. The study utilized a two-arm randomized control research design in which 40 participants were randomly assigned into one of two groups, either the control group (n = 20) or the treatment group (n = 20). All tests and assessments were performed before and after intervention for both groups. The control group walked less than 5000 steps every day for one month with a 20 min rest during the exercise session, while the treatment group walked more than 12,000 steps every day for the same time and exercise task session. The students’ steps were monitored using an Apple watch. There was a significant decrease in the IgG antibody level in the treatment group compared to the control group (p < 0.001). The IgM antibody level of all groups did not show any significant difference before starting the intervention. However, there was a significant (p < 0.05) decrease in the IgM level of the treatment group after treatment compared to before treatment. Moreover, there was a significant decrease in the treatment group’s stress level and sleep disruption, indicating better sleep quality, compared to the control group (p < 0.035). The levels of IgG and IgM did not improve for the treatment group. However, the treatment group improved their stress level and sleep disruption. Therefore, further rigorous research is needed to investigate vaccine efficacy among more physically active people. Full article

Brucellosis is a zoonotic disease caused by Gram-negative bacteria. Most of the brucellosis vaccines in the application are whole-bacteria vaccines. Live-attenuated vaccines are widely used for brucellosis prevention in sheep, goats, pigs, and cattle. Thus, there is also a need for an adjuvanted vaccine for human brucellosis, because the attenuated Brucella vaccines now utilized in animals cause human illness. Here, we developed a live-attenuated Brucella suis strain 2 vaccine (S2) adjuvanted with Ag85a (Ag85a-S2). We found that Ag85a-S2 activated cGAS-STING pathways both in intestinal mucosal cells in vivo and in the BMDM and U937 cell line in vitro. We demonstrated that the cGAS knockout significantly downregulated the abundance of interferon and other cytokines induced by Ag85a-S2. Moreover, Ag85a-S2 triggered a stronger cellular immune response compared to S2 alone. In sum, Ag85a-S2-mediated enhancement of immune responses was at least partially dependent on the cGAS-STING pathway. Our results provide a new candidate for preventing Brucella pathogens from livestock, which might reduce the dosage and potential toxicity compared to S2. Full article

Between the first case of COVID-19 in January 2020 and the end of 2021, Thailand experienced four waves of the epidemic. The third and fourth waves were caused by the alpha and delta strains from April 2021 to November 2021. Serosurveillance studies provide snapshots of the true scale of the outbreak, including the asymptomatic infections that could not be fully captured by a hospital-based case detection system. We aimed to investigate the distribution of SARs-CoV-2 seroprevalence in unvaccinated adults after the delta wave outbreak. From November to December 2021, we conducted a cross-sectional survey study in 12 public health areas (PHAs) across Thailand. A total of 26,717 blood samples were collected and tested for SARs-CoV-2 antibodies (anti-S IgG) using a qualitative immunoassay. The results showed that seropositive prevalence in this cohort was 1.4% (95% CI: 1.24 to 1.52). The lowest prevalence was in the northern region (PHA 1) and in central Thailand (PHA 3) at 0.4% (95% CI: 0.15 to 0.95), while the highest was in the southern region of Thailand (PHA 12) at 5.8% (95% CI: 4.48 to 7.29). This seropositive prevalence was strikingly lower than the reports from other countries. Our serosurveillance results suggest that the vaccination of unvaccinated groups should be accelerated, especially in the public health areas with the lowest seroprevalence. Full article

Healthcare workers (HCWs) are a vulnerable and critical population in the ongoing response to the SARS-CoV-2 pandemic. We aimed to estimate the seroprevalence in HCWs considering all of their previous contacts with the SARS-CoV-2 virus and/or the immunity acquired through their immunization against COVID-19 before the advent of the Omicron variants BA.4/BA.5. Serum samples were collected from 28 March to 10 June 2022. We covered 25% out of all the people who worked in some of the government healthcare centers (primary, secondary, and tertiary level) across the entire Autonomous Province of Vojvodina (Northern Serbia). Two serological tests (Anti-SARS-CoV-2 QuantiVac ELISA and LIAISON^® SARS-CoV-2 TrimericS) were used to detect anti-spike IgG antibodies. The overall prevalence of the SARS-CoV-2 antibody among the 6936 HCWs was 92.96% [95% CI 92.33–93.55]. Regarding the type of serological test, there was a statistically significant (p = 0.0079) difference of the seropositivity obtained by the LIAISON^® SARS-CoV-2 TrimericS (93.87%, 95% CI 92.97–94.69) and Anti-SARS-CoV-2 QuantiVac ELISA (92.23%, 95% CI 91.34–93.06) tests. Seropositivity to SARS-CoV-2 significantly (p < 0.0001) increased with the number of SARS-CoV-2 infections combined with the number of doses of the SARS-CoV-2 vaccines received. A vast majority of the HCWs in Vojvodina had detectable levels of antibodies to the spike protein of SARS-CoV-2, but despite this high seropositivity, it is unknown whether this herd immunity among HCWs is protective against the new variants of concern. Further research should evaluate the rates of reinfections and the associated severity of COVID-19 caused by the Omicron sublineages and/or new variants of SARS-CoV-2 among HCWs. Full article

Background: It is unclear whether multiple sclerosis (MS) patients receiving ofatumumab mount an immune response after SARS-CoV-2 mRNA vaccination. Methods: KYRIOS is an ongoing, multicenter, open-label, prospective clinical study on immune responses in MS patients after initial or booster SARS-CoV-2 mRNA vaccination prior to (cohort 1) or during (cohort 2) ofatumumab treatment. We report one-week and one-month results of the initial vaccination. A comparison with patients vaccinated while receiving beta-interferon, glatiramer acetate, dimethyl fumarate, teriflunomide or no treatment was included (cohort 3). Results: In total, 11 patients received their initial vaccination during the study. The primary endpoint of SARS-CoV-2-specific T-cells at month 1 was reached by 80.0% of patients in cohort 1 (N = 6) and 100.0% in cohort 2 (N = 5). T-cell reactivity peaked at week 1. All cohort 1 patients reached seroconversion for SARS-CoV-2 neutralizing antibodies at week 1 and month 1. In cohort 2, neutralizing antibodies increased in all patients and exceeded the cut-off for seropositivity in 40.0% of patients at week 1 and 25.0% at month 1. Immune responses in cohort 3 were comparable to cohort 1. Conclusion: Presence of T-cell response and increase in levels of neutralizing antibodies, although less pronounced compared to controls, suggest that MS patients receiving ofatumumab are able to mount an immune response to SARS-CoV-2 mRNA vaccination. Full article

Early successes in controlling the COVID-19 pandemic have prevented Republic of Korea from implementing a prompt, large-scale vaccine rollout to the public. The influence of traditional media on public opinion remains critical and substantial in Republic of Korea, and there have been heated debates about vaccination in traditional media reports in Korea. Effective and efficient public health communication is integral in managing public health challenges. This study explored media reports on the COVID-19 vaccines during the pandemic in Republic of Korea. 12,399 media news reports from May 2020 to September 2021 were collected. An LDA topic model was applied in order to analyze and compare the topics drawn from each study phase using words from the unstructured text data. Although media reports from before the national vaccination implementation focused on the development and rollout of COVID-19 vaccines, diverse topics were reported without any overlap. After the vaccination rollout, the biggest concern was the side effects of the COVID-19 vaccine. In sum, Republic of Korea’s major media outlets reported on diverse topics rather than generating a common discourse about topics related to COVID-19 vaccination. Full article

Live immunization is contraindicated in patients with DiGeorge syndrome (DGS). We retrospectively investigated the occurrence of adverse events after live immunization in patients with DGS in Korea. The data of patients matching the International Classification of Disease-10 code of DGS (D82.1) at Severance Hospital Seoul, Korea, were extracted; patients without genetically diagnosed DGS were excluded. Based on T cell immunity status, the included patients were categorized into group A (CD3 < 500 or CD8 < 200 cells/mm³); group B (CD3 ≥ 500 and CD8 ≥ 200 cells/mm³); or group C (unknown). Among 94 patients, 38 (~40%, group A: 8 [21%]; group B: 30 [79%]) underwent immunological testing and 73 (~80%) received at least one live immunization (measles–mumps–rubella vaccination was most common [66/94, ~70%]). Fifty adverse events (fever [n = 29], upper respiratory infection [n = 9], diarrhea [n = 4], rash [n = 3], thrombocytopenia [n = 3], injection site pus [n = 1], and febrile convulsion [n = 1]) were observed; 13 (26%) occurred in group A, with no significant difference in incidence between groups A and B. Serious adverse events, including intensive care unit hospitalization or death, or diseases due to vaccine strains were not observed. In this study, live immunization was well tolerated by patients with partial DGS. Full article

A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of multidrug therapy is needed, which has many drawbacks. At present, vaccines are proposed as an adjunct to chemotherapy to protect populations with an LTBI and delay its recurrence. In this study, we analyzed the protective effect of a novel subunit vaccine, AEC/BC02, in a guinea pig latent infection model. Through the optimization of different chemotherapy durations and immunization times, it was found that 4 weeks of administration of isoniazid–rifampin tablets combined with three or six injections of the vaccine could significantly reduce the gross pathological score and bacterial load in organs and improve the pathological lesions. This treatment regimen had a better protective effect than the other administration methods. Furthermore, no drug resistance of Mycobacterium tuberculosis was detected after 2 or 4 weeks of administration of the isoniazid–rifampin tablets, indicating a low risk of developing drug-resistant bacteria during short-term chemotherapy. The above results provided the foundation for an AEC/BC02 clinical protocol. Full article

(1) Background: The incidence of Lyme borreliosis (LB) is increasing in Europe. The new LB vaccine is still in clinical development, thus the dissemination of knowledge about the disease is essential. We assessed the knowledge, attitudes and preventive practices (KAP) against tick-borne diseases (TBDs) of people living in the endemic area in northeastern Poland. (2) Methods: We surveyed 406 adults using a 37-item anonymous paper survey. The data were analyzed with regression models. (3) Results: The two most popular knowledge sources were the Internet and doctors, selected by 77.8% and 53.4%, respectively. Respondents felt moderately knowledgeable about TBDs and tick bite prophylaxis (median scores 5/10, and 6/10, respectively), considered TBDs to be a significant health threat (median 8/10), attributed high risk to tick mouthparts remaining in the skin after tick removal (median 10/10), and shared multiple misconceptions regarding LB transmission, symptoms, and management. General knowledge scores (GKS) about TBDs and tick protection practices scores (TPS) were moderate (65.0%; IQR, 55.8–71.7%, 63.6%; 54.5–72.7%, respectively). Only 48.0% had a positive attitude towards TBE vaccination. A recent tick-bite was associated with higher GKS (OR, 2.55; 95% CI, 1.27–5.10; p = 0.008), higher TPS (OR 4.76, 95% CI, 2.0–11.1; p < 0.001), and a positive attitude towards TBE vaccine (OR 2.10, 1.07–4.10, p = 0.030). A positive vaccine attitude was also associated with obtaining TBD knowledge from doctors and other verified sources (OR, 2.654, 1.66–4.23; p < 0.001). Age, place of residence, and frequent exposure to ticks in green areas were not associated with GKS, TPS, nor vaccine attitude. (4) Conclusions: Increased risk perceptions are associated with adoption of behaviors preventing TBDs. Medical professionals play an important role in communicating knowledge about TBDs. There is a need to revise current communication strategies with respect to tick bites and prevention of LB and other TBDs. Full article

Unlike previous viral diseases, COVID-19 has an “asymptomatic” group that has no symptoms but can still spread the disease to others at the same rate as symptomatic patients who are infected. In the literature, the mass action or standard incidence rates are considered for compartmental models with asymptomatic compartment for studying the transmission dynamics of COVID-19, but the quarantined adjusted incidence rate is not. To bridge this gap, we developed a Susceptible Asymptomatic Infectious Quarantined (SAIQ) model with a Quarantine-Adjusted (QA) incidence to investigate the emergence and containment of COVID-19. COVID-19 models are investigated using various methods, but only a few studies take into account closed-form solutions. The knowledge of closed-form solutions simplifies the construction of the various epidemic indicators that describe the epidemic phenomenon and makes the sensitivity analysis to variations in the data under consideration possible. The closed-form solutions of the systems of four nonlinear first-order ordinary differential equations (ODEs) are established. The Epidemic Peak (EP), Force of Infection (FOI) and Rate of Infection (ROI) are the important indicators for the control and prevention of disease. We examined these indicators using closed-form solutions and particular parameter values. Different disease control scenarios are thoroughly examined. The four scenarios to analyze COVID-19 propagation and containment are (i) lockdown, (ii) quarantine and other preventative measures, (iii) stabilizing the basic reproduction rate to a level where the pandemic can be contained and (iv) containing the epidemic through an appropriate combination of lockdown, quarantine and other preventative measures. Full article

In low- and middle-income countries, diarrhoeal diseases are the second most common cause of mortality in children, mainly caused by enterotoxin-producing bacteria, such as Shigella, Vibrio, Salmonella, and Escherichia coli. Cholera and traveller’s diarrhoea are caused by Vibrio cholerae (O1 and O139 serogroups) and enterotoxigenic Escherichia coli (ETEC), respectively. The cholera toxin (CT) produced by V. cholerae and the heat-labile enterotoxin (LT) of ETEC are closely related by structure, function, and the immunological response to them. There is no exclusive vaccine for ETEC; however, cholera vaccines based on the CT-B component elicit a short-term cross-protection against ETEC infection. In this context, the cross-protective efficacy of MyChol^TM, a prototype cold-chain-free, live-attenuated, oral cholera vaccine against V. cholerae O139 was evaluated in BALB/c mice. The 100% lethal dose (LD₁₀₀) of 10⁹ CFU/mL of the ETEC H10407 strain was used for the challenge studies. The mice immunised with MyChol™ survived the challenge by producing anti-CT antibodies, which cross-neutralised the LT toxin with no body weight loss and no sign of diarrhoea. Compared to unimmunised mice, the immunised mice elicited the neutralising antitoxin that markedly decreased ETEC colonisation and fluid accumulation caused by ETEC H10407 in the intestines. The immunised mice recorded higher antibody titres, including anti-CT IgG, anti-LT IgG, anti-CT-B IgG, and anti-LTB IgG. Only a two-fold rise in anti-CT/CT-B/LT/LT-B IgA was recorded in serum samples from immunised mice. No bactericidal antibodies against ETEC H10407 were detected. This investigation demonstrates the safety, immunogenicity, and cross-protective efficacy of MyChol^TM against the ETEC H10407 challenge in BALB/c mice. Full article

Most Japanese adults are vaccinated twice with the Sabin trivalent oral polio vaccine. Booster vaccination is recommended for Japanese travelers to polio-endemic/high-risk countries. We assessed the catch-up immunization of healthy Japanese adults aged ≥20 years with two doses of standalone conventional inactivated polio vaccine (cIPV). Immunogenicity was evaluated by serum neutralization titers (pre-booster vaccination, 4–6 weeks after each vaccination) against type 1, 2, and 3 poliovirus strains. The participants were 61 healthy Japanese adults (26 men/35 women; mean age ± standard deviation age 35.8 ± 8.0 years). Seropositivity rates (percentage of participants with anti-poliovirus antibody titers ≥1:8) pre-vaccination were 88.5%, 95.1%, and 52.5% for Sabin strains (type 1, 2, and 3); 72.1%, 93.4%, and 31.1% for virulent poliovirus strains (type 1: Mahoney; type 2: MEF-1; and type 3: Saukett); and 93.4%, 93.4%, 93.4%, and 88.5% for type 2 vaccine-derived poliovirus strains (SV3128, SV3130, 11,196, and 11,198). After one cIPV dose, all seropositivity rates increased to 98.4–100.0%. After two cIPV doses, the seropositivity rates reached 100% for all strains. cIPV was well tolerated, with no safety concerns. Catch-up immunization with standalone cIPV induced robust immune responses in Japanese adults, indicating that one booster dose boosted serum-neutralizing antibodies to many strains. Full article

This study aims to provide comparative data on clinical features and in-hospital outcomes among U.S. adults admitted to the hospital with COVID-19 and influenza infection using a nationwide inpatient sample (N.I.S.) data 2020. Data were collected on patient characteristics and in-hospital outcomes, including patient’s age, race, sex, insurance status, median income, length of stay, mortality, hospitalization cost, comorbidities, mechanical ventilation, and vasopressor support. Additional analysis was performed using propensity matching. In propensity-matched cohort analysis, influenza-positive (and COVID-positive) patients had higher mean hospitalization cost (USD 129,742 vs. USD 68,878, p = 0.04) and total length of stay (9.9 days vs. 8.2 days, p = 0.01), higher odds of needing mechanical ventilation (OR 2.01, 95% CI 1.19–3.39), and higher in-hospital mortality (OR 2.09, 95% CI 1.03–4.24) relative to the COVID-positive and influenza-negative cohort. In conclusion, COVID-positive and influenza-negative patients had lower hospital charges, shorter hospital stays, and overall lower mortality, thereby supporting the use of the influenza vaccine in COVID-positive patients. Full article

Introduction: The BNT162b2 vaccination studies did not specifically focus on groups that were heavily exposed to SARS-CoV-2 infection. Therefore, we aimed to assess the safety and efficacy of the BNT162b2 vaccine among healthcare workers (HCWs). Methods: Study participants were recruited from hospital employees who received BNT162b2 vaccination at the Hospital for Infectious Diseases in Warsaw. Blood samples were collected before and after each vaccination dose. At each timepoint, the levels of anti-SARS CoV-2 IgM, anti-n SARS-CoV-2 IgG, and S-RBD antibodies were measured. Data on concomitant diseases and the vaccine’s adverse events (VAE) were collected after each vaccination dose. In the statistical analyses, non-parametric tests were used. Results: In total, 170 healthcare workers were included in the analysis. Their median age was 51 years (interquartile range (IQR): 41–60 years); most of them were women (n = 137, 80.6%) working in direct contact with patients (n = 137, 73.2%); and 46 (27.0%) had concomitant diseases. More than one fifth of subjects had COVID-19 before their first dose of vaccination (n = 38, 22.6%). In terms of immunological responses, our investigations showed a high level of efficacy for the BNT162b2 mRNA vaccination as measured by S-RBD antibody concentrations: these were positive in 100% of participants 14 days after the second dose of the vaccine. It was also observed that employees with high S-RBD antibodies (>=433 BAU/mL) were more likely to be COVID-19 convalescents before receiving the first vaccine dose (p < 0.001). Conclusion: The BNT162b2 vaccine is safe and effective among HCWs. Vaccine adverse events occurred, but serious events were not observed. Moreover, the BNT162b2 vaccine is effective against symptomatic and severe COVID-19—none of the workers that acquired a SARS-CoV-2 infection after vaccination required hospitalization or medical care. We also observed higher immunological responses among COVID-19 convalescents. Full article

Background: The emergence of COVID-19 has been a major challenge to public health and the world economy. During a wave of COVID-19, the usage of widespread vaccination procedures and broader coverage to the whole of humanity will be made possible if the general population has access. An intended effect of vaccination is to provide “herd immunity,” which protects those who have not been vaccinated along with those who have been. However, some concerns regarding the safety and efficacy of COVID-19 vaccines were raised. Aim: This study aims to provide evidence on the short-term safety and efficacy of four types of vaccines that are officially approved by the Ministry of Health in the United Arab Emirates (UAE). These include Sinopharm, Sputnik V, Pfizer, and AstraZeneca. Method: This study utilized a cross-sectional descriptive design. Data on the efficacy and short-term protection of COVID-19 vaccines on vaccinated citizens and residents (n = 764) of the UAE were collected between February and April 2021. Participants were conveniently approached using a Google Forms survey, where they responded to a semi-structured questionnaire pertaining to socio-demographic questions and in-depth questions related to COVID-19, including whether they suffer from any comorbidities, the most commonly encountered post-vaccination side effects, and the severity of their symptoms, using a 5-point Likert scale. Results were analyzed using SPSS version 24, calculations of p-values and descriptive statistics were used for data differentiation. Results: The majority of the participants (n = 612 or 94.4%) stated that they did not become reinfected after receiving two doses of COVID-19 vaccine. In addition, the incidence of being hospitalized after vaccination was negligible. In terms of adverse effects, the most common individually reported side effects, regardless of the vaccination type, included “pain at the site of injection”, followed by “general fatigue”, then “lethargy”. Moreover, most of these side effects occurred after the second dose of the vaccine, irrespective of the type of vaccine. Females were found to be more susceptible to the adversities of COVID-19 vaccination. The occurrence of side effects was not found to be related to the nationality/ethnicity of the vaccine recipient. Furthermore, none of the vaccines affected sleep pattern, since a significant number of respondents reported a regular sleep pattern after being vaccinated. The majority respondents who received two doses of vaccination (n = 585 or 76.6%) reported that they did not become infected post vaccination, regardless the type of vaccine received, whereas only (n = 11 or 1.9%) were reinfected with COVID-19 after 2–4 weeks. Conclusion: The findings of this study suggest that vaccines can offer short-term protection against COVID-19 reinfection. Moreover, both the first- and second-vaccination side effects were described as very mild to moderate, which indicates tolerability. These data may strengthen the public confidence in receiving vaccinations. Full article

Malignant catarrhal fever (MCF) is a complex and often fatal disease of ungulates. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate a sheep-associated MCF (SA-MCF) vaccine candidate targeting ovine herpesvirus 2 (OvHV-2) glycoprotein B (gB). Rabbits were used as a laboratory animal model to test the safety, immunogenicity, and protective efficacy of a chimeric virus consisting of a recombinant, non-pathogenic strain of alcelaphine herpesvirus-1 encoding OvHV-2 ORF8 to express gB (AlHV-1^∆ORF73/OvHV-2-ORF8). Viral-vectored immunizations were performed by using the AlHV-1^∆ORF73/OvHV-2-ORF8 chimera alone or as a DNA prime (OvHV-2-ORF8)-virus boost regimen. The viral vector was inoculated by intravenous or intramuscular routes and the DNA was delivered by intradermal shots using a gene gun. The vaccine candidates were deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced by all immunogens. At three weeks post-final immunization, all animals were challenged intranasally with a lethal dose of OvHV-2. MCF protection rates ranging from 66.7% to 71.4% were observed in vaccinated rabbits, while all mock-vaccinated animals developed the disease. The significant protective efficacy obtained with the vaccine platforms tested in this study encourages further trials in relevant livestock species, such as cattle and bison. Full article

Both adaptive and innate immunity responses are necessary for the efficient elimination of different pathogens. However, the magnitude, quality and desired type of immune response specific to the co-administered antigen is largely determined by adjuvants. BC02 (BCG CpG DNA compound adjuvants system 02) is a novel compound adjuvant with independent intellectual properties, which is composed of BCG CpG DNA biological adjuvant with Al(OH)₃ inorganic salt adjuvant acting as a delivery system. Its safety and strong adjuvant efficacy have been effectively verified in preclinical and clinical trials (Phase Ib, ClinicalTrials.gov Identifier: NCT04239313 and Phase II, ClinicalTrials.gov Identifier: NCT05284812). In this study, we report the level of cell-mediated immunity (CMI) and humoral immune response induced by the BC02 novel adjuvant combined with different doses of varicella-zoster virus (VZV) glycoprotein E (gE) in a mouse model. In addition, we conducted preliminary in vitro experiments to explore the enhancement of RAW264.7 cell immune activity by BC02 adjuvanted-gE experimental vaccine to activate innate immune response. The results showed that the BC02-adjuvanted low, medium or high dose of gE were highly effective in eliciting both CMI and humoral immune responses to the immunized mice, respectively. The production of gE-specific IFN-γ and IL-2-specific T cells was established within 28 days after booster immunization. In particular, the effect of BC02-adjuvanted medium dose of gE has been shown to be more prominent. Meanwhile, fluorescent antibody to membrane antigen (FAMA) and serum antibody plaque reduction tests have also shown that the BC02 adjuvanted-medium dose of gE antigen could induce the secretion of neutralizing antibodies against clinically isolated VZV strains in mice. In addition, our findings have shown that 1/25 dose of gE+BC02 medium dose experimental vaccine can significantly induce the secretion of innate immune cytokines TNF-A, MCP-1, IL-6 and GM-CSF and up-regulate the costimulatory molecules CD40, CD80 and I-A/I-E on RAW264.7 cells; and it has also been activated to form M2 macrophages. At the same time, RAW264.7 cells were stimulated for 12 h, and their phagocytosis was significantly enhanced. Taken together, these results suggest that the BC02 compound adjuvant offers a strategy to induce an appropriate innate and adaptive immunity against the different doses of the VZV gE protein to improve subunit vaccine efficacy, and BC02 may be a promising adjuvant candidate for subunit HZ vaccines. Full article

Background: Poliovirus post-eradication containment of wild-type 2 poliovirus (PV2) requires the destruction of all materials containing, or potentially containing, PV2. Acute flaccid paralysis (AFP) cases in Israel between 1973 and 1988 were caused by all three serotypes; thus, isolates from cases and case-contacts were either PV2 or potentially contaminated with PV2. Aims: To provide a proof-of-concept that whole genome sequences (WGS) of wild-type 3 poliovirus (PV3s) could be salvaged from the RNA extracted directly from archived poliovirus stocks avoiding re-amplification of neurovirulent viruses, we link WGSs to case histories and determine the phylogenetic relationships among the PV3s. Methods: Data retrieved from 427 poliovirus-positive cases reported between 1973 and 1988 identified 85 PV3-associated cases. A total of 71 archived PV3 isolates were available from PV3-positive cases and contacts. WGSs were obtained by NGS from cDNA libraries constructed from RNA extracted directly from archived viral stocks. Sequences were subjected to phylogenetic analysis and linked to case data. Results: WGSs were successfully constructed for 55 isolates. Phylogenetic analysis revealed the circulation of seven lineages of PV3. One lineage, with 23 isolates, presented as an outbreak of six-year duration. Isolates from six other lineages were consistent with subsequent separate introductions, sporadic cases, and limited transmission. Recombinant vaccine-like PV3 recombinants were isolated from some cases. Conclusions: Whole or near-whole genome sequence information, obtained from RNA extracted directly from the archived material, safely provided detailed genetic information linked to patient data from a time when limited sequence information was previously available and revealed the pattern of transmission of wild PV3 in Israel. Full article