Investigating Field Efficacy and Safety of Conjunctival Brucella abortus S19 Vaccine in Cattle

Background: Vaccination is the most fundamental strategy in the control and eradication of brucellosis. Several vaccination programs with different vaccines have been carried out in many countries in which brucellosis continues to be a problem in livestock. One of the recommended vaccines against brucellosis in cattle is the live Brucella abortus S19 vaccine. The aim of this study is to evaluate the results of field safety and efficacy trials for the conjunctival Brucella abortus S19 vaccine prior to the mass vaccination program. Methods: In this study, 81 female cattle were vaccinated with a reduced dose of Brucella abortus S19 vaccine with the conjunctival route. The immune response after vaccination was investigated by suggested serological tests; namely, Rose Bengal Plate Test, Serum Agglutination Test and Complement Fixation Test. Result: No adverse effect was observed within the scope of safety. Isolation of vaccine strain was observed only in a milk sample of lactating animals. Excluding the diagnosis criteria of the serological tests, humoral immune response was observed in most of the animals by all the serological tests one month after vaccination. Antibody levels lasted approximately 4 months after vaccination. In conclusion, the results of this study demonstrated that besides vaccine-induced antibodies, the vaccine including changes in dose and administration way in this study did not cause any significant risks for the target animals.

COVID-19 Vaccination Uptake among individuals with Immune-Mediated Inflammatory Diseases in Ontario, Canada between December 2020 and October 2021: A population-based analysis

Objective We assessed COVID-19 vaccine uptake among individuals with immune-mediated inflammatory diseases (IMID) and the Ontario general population. Methods We studied all residents 16 years and older who were alive and enrolled in Ontario's universal health insurance plan as of December 14, 2020 when vaccination commenced (n=12,435,914). Individuals with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) were identified using established disease-specific case definitions applied to health administrative data. Vaccination status was extracted from the provincial COVaxON registry. Weekly cumulative proportions of first and second doses up until October 3, 2021 were expressed as the vaccinated percentage of each disease group, and compared to the general Ontario population, and stratified by age. Results By October 3, 2021, the cumulative percentage with at least one dose was 82.1% for the general population, 88.9% for RA, 87.4% for AS, 90.6% for PsA, 87.3% for PsO, and 87.0% for IBD. There was also a higher total cumulative percentage with two doses among IMIDs (83.8-88.2%) vs the general population (78.0%). The difference was also evident when stratifying by age. Individuals with IMIDs in the youngest age group initially had earlier uptake than the general population but remain the lowest age group with two doses (70.6% in the general population vs. 73.7-79.2% across IMID groups). Conclusion While implementation of COVID-19 vaccination programs has differed globally, these Canadian estimates are the first to reassuringly show higher COVID-19 vaccine uptake among individuals with IMIDs.

Students as Community Vaccinators: Implementation of a Service-Learning COVID-19 Vaccination Program

Background: Service-learning is an integral component of medical education. While the COVID-19 pandemic has caused massive educational disruptions, it has also catalyzed innovation in service-learning as real-time responses to pandemic-related problems. For example, the limited number of qualified providers was a potential barrier to local and national SARS-CoV-2 vaccination efforts. Foreseeing this hurdle, New York State temporarily allowed healthcare professional trainees to vaccinate, enabling medical students to support an overwhelmed healthcare system and contribute to the community. Yet, it was the responsibility of medical schools to interpret these rules and implement the vaccination programs. Here the authors describe a service-learning vaccination program directed towards underserved communities. Methods: Weill Cornell Medicine (WCM) rapidly developed a faculty-led curriculum to prepare students to communicate with patients about the COVID-19 vaccines and to administer intramuscular injections. Qualified students were deployed to public vaccination clinics located in underserved neighborhoods across New York City in collaboration with an established community partner. The educational value of the program was evaluated with retrospective survey. Results: Throughout the program, which lasted from February to June 2021, 128 WCM students worked at 103 local events, helping to administer 26,889 vaccine doses. Analysis of student evaluations revealed this program taught fundamental clinical skills, increasing comfort giving intramuscular injection from 2% to 100% and increasing comfort talking to patients about the COVID-19 vaccine from 30% to 100%. Qualitatively participants described the program as a transformative service-learning experience. Conclusion: As new virus variants emerge, nations battle recurrent waves of infection, and vaccine eligibility expands to include children and boosters, the need for effective vaccination plans continues to grow. The program described here offers a novel framework that academic medical centers could adapt to increase vaccine access in their local community and provide students with a uniquely meaningful educational experience.

Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2

Although not being the first viral pandemic to affect humankind, we are now for the first time faced with a pandemic caused by a coronavirus. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the COVID-19 pandemic, which caused more than 4.5 million deaths worldwide. Despite unprecedented efforts, with vaccines being developed in a record time, SARS-CoV-2 continues to spread worldwide with new variants arising in different countries. Such persistent spread is in part enabled by public resistance to vaccination in some countries, and limited access to vaccines in other countries. The limited vaccination coverage, the continued risk for resistant variants, and the existence of natural reservoirs for coronaviruses, highlight the importance of developing additional therapeutic strategies against SARS-CoV-2 and other coronaviruses. At the beginning of the pandemic it was suggested that countries with Bacillus Calmette-Guérin (BCG) vaccination programs could be associated with a reduced number and/or severity of COVID-19 cases. Preliminary studies have provided evidence for this relationship and further investigation is being conducted in ongoing clinical trials. The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells. In order to identify potential targets of T cell cross-reactivity, we implemented an in silico strategy combining sequence-based and structure-based methods to screen over 13,5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. Our study produced (i) a list of immunogenic BCG-derived peptides that may prime T cell cross-reactivity against SARS-CoV-2, (ii) a large dataset of modeled peptide-HLA structures for the screened targets, and (iii) new computational methods for structure-based screenings that can be used by others in future studies. Our study expands the list of BCG peptides potentially involved in T cell cross-reactivity with SARS-CoV-2-derived peptides, and identifies multiple high-density “neighborhoods” of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.

Effects of vaccination and non-pharmaceutical interventions and their lag times on the COVID-19 pandemic: Comparison of eight countries

Many countries implemented measures to control the COVID-19 pandemic, but the effects of these measures have varied greatly. We evaluated the effects of different policies, the prevalence of dominant variants (e.g., Delta), and vaccination on the characteristics of the COVID-19 pandemic in eight countries. We quantified the lag times of different non-pharmaceutical interventions (NPIs) and vaccination using a distributed lag non-linear model (DLNM). We also tested whether these lag times were reasonable by analyzing changes in daily cases and the effective reproductive number (Rt)over time. Our results indicated that the response to vaccination in countries with continuous vaccination programs lagged by at least 40 days, and the lag time for a response to NPIs was at least 14 days. A rebound was most likely to occur during the 40 days after the first vaccine dose. We also found that the combination of school closure, workplace closure, restrictions on mass gatherings, and stay-at-home requirements were successful in containing the pandemic. Our results thus demonstrated that vaccination was effective, although some regions were adversely affected by new variants and low vaccination coverage. Importantly, relaxation of NPIs soon after implementation of a vaccination program may lead to a rebound.

Robust and durable serological response following pediatric SARS-CoV-2 infection

The quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3–4 months and 11–12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11–12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

VarLOCK - sequencing independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance

The COVID-19 pandemic continues to pose a threat to the general population. The ongoing vaccination programs provide protection to individuals and facilitate the opening of society and a return to normality. However, emergent and existing SARS-CoV-2 variants capable of evading the immune system endanger the efficacy of the vaccination strategy. To preserve the efficacy of SARS-CoV-2 vaccination globally, aggressive and effective surveillance for known and emerging SARS-CoV-2 Variants of Concern (VOC) is required. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. In this work, we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to allow rapid and sensitive discrimination of VOCs, that can be used at point of care and/or implemented in the pipelines of small or large testing facilities, and even determine proportion of VOCs in pooled population-level wastewater samples. This technology aims to complement the ongoing sequencing efforts to allow facile and, crucially, rapid identification of individuals infected with VOCs to help break infection chains. Here, we show the optimisation of our VarLOCK assays (Variant-specific SHERLOCK) for multiple specific mutations in the S gene of SARS-CoV-2 and validation with samples from the Cardiff University Testing Service. We also show the applicability of VarLOCK to national wastewater surveillance of SARS-CoV-2 variants. In addition, we show the rapid adaptability of the technique for new and emerging VOCs such as Omicron.

Cervical Screening in North Sardinia (Italy): Genotype Distribution and Prevalence of HPV among Women with ASC-US Cytology

The assessment of human papillomavirus (HPV) genotype dynamics could support the adoption of more tailored preventive actions against cervical cancer. The aim of the study was to describe the prevalence of HPV infection, HPV genotype distribution, and the epidemiological characteristics of women with ASC-US cytology since the introduction of HPV-DNA testing in Sardinia (Italy), (March 2016–December 2020). Specimens were tested by RT-PCR for 14 high-risk HPV genotypes. A total of 1186 patients were enrolled, with a median (IQR) age of 41 (38–48) years. Of these women, 48.1% were positive for at least one HPV genotype; 311 (26.2%) women were vaccinated with a median (IQR) age of 38 (30/47) years. The percentage of prevalence of HPV-16, -31, -66, -56, and -51 was 36.3%, 18.7%, 11.9%, 11.4% and 10.7%, respectively. The highest prevalence of infection was found in women aged <41 years, and single women. Moreover, women aged >41 years (OR: 0.51, 95% CI: 0.31–0.86; p-value: 0.01), having parity (OR: 0.57, 95% CI: 0.34–0.96, p-value: 0.04), and higher educational level (OR: 0.39, 95% CI: 0.18–0.87; p-value: 0.02) were associated with a lower CIN2+ risk. We did not find a significant difference in terms of prevalence of HPV-16 infection between vaccinated and non-vaccinated (18.3% vs. 17.1%; p-value < 0.001). Our results support the adoption of nonavalent HPV-vaccine to prevent the most prevalent infections caused by HPV-16 and -31 genotypes and underscore the need of surveillance to implement tailored vaccination programs and preventive strategies.