Dose Of Vaccine Research Articles

A single immunization of Borreliella burgdorferi-infected mice with Vanguard crLyme elicits robust antibody responses to diverse strains and variants of outer surface protein C.

Lyme disease, caused by Borreliella burgdorferi and related species, is a growing health threat to companion animals across North America and Europe. Vaccination is an important preventive tool used widely in dogs living in, or near, endemic regions. In this report, we assessed anti-outer surface protein (Osp) A and anti-OspC antibody responses in B. burgdorferi-infected and -naïve mice (C3H/HeN) after immunization with a murine-optimized single dose of the Lyme disease subunit vaccine, Vanguard crLyme. crLyme is comprised of OspA and an OspC chimeritope-based immunogen designated as CH14. Mice that were infected and immunized developed higher levels of anti-OspC antibodies (Abs) than those infected only or that received one vaccine dose. The anti-OspC Abs that developed in the infected/immunized mice bound to all OspC variants tested (n = 22), whereas OspC Abs in serum from infected mice bound predominantly to the OspC variant (type A) produced by the infecting B. burgdorferi strain. Consistent with the absence of OspA expression in infected mammals, none of the infected mice developed Abs to OspA and did not develop anti-OspA Abs after single dose immunization. Lastly, serum from infected/immunized mice displayed significantly higher and broader killing activity than serum from non-immunized infected mice. The results of this study demonstrate that a single vaccination of actively infected mice results in strong anti-OspC Ab responses. This study contributes to our understanding of Ab responses to vaccination in actively infected mammals.

Immunogenicity of Comirnaty Omicron XBB.1.5 booster COVID-19 mRNA vaccine in long-term survivors after allogeneic hematopoietic stem cell transplantation

Primary mRNA vaccination against COVID-19 typically involves three doses for immunocompromised individuals, including hematopoietic stem cell transplantation (allo-HSCT) recipients. However, optimal subsequent boosting strategies remain unclear. This study aimed to assess the immunogenicity of a booster dose using the most recently updated vaccine (Comirnaty Omicron XBB.1.5) among long-term allo-HSCT survivors having previously received multiple mRNA vaccine doses, in median 4 (2–6). Thirty-four allo-HSCT recipients were enrolled at Sahlgrenska University Hospital, and peripheral blood samples were collected immediately before and four weeks after booster. Antibodies against the receptor-binding domain (anti-RBD) of spike 1 (S1) and nucleocapsid, as well as S1-specific ex vivo T-cell responses, were evaluated. Adverse events were monitored. Despite a median of 13 months since the prior vaccine dose, both humoral and T-cell responses against S1 were present in the pre-booster samples in all but two participants, who suffered from severe chronic Graft-versus-host disease. Notably, 62% of participants had a previously confirmed COVID-19 infection. Significantly higher pre-booster antibody levels were observed in women than men (p = 0.003). Booster dosing strengthened specific antibody and T cell responses and equalized pre-booster gender differences, although responses remained significantly lower among those receiving immunosuppressive treatment (p = 0.041). In a population of long-term allo-HSCT survivors, the majority of whom had a prior confirmed COVID-19 infection, both pre- and post-booster immune responses were robust. However, patients undergoing immunosuppressive treatment for GvHD exhibited significantly weaker responses.

MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2

BackgroundCancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.Patients and methodsPlasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR.ResultsWe found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles.ConclusionsMiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

COVID-19 vaccine hesitancy in Ethiopia: a latent class analysis

BackgroundDespite evidence demonstrating the effectiveness of the COVID-19 vaccine, vaccine hesitancy has emerged as a major challenge for vaccine uptake. The objective of this study was to classify latent typologies of vaccine hesitant adults in Ethiopia and identify predictors of the latent classes.MethodsWe employed a cross-sectional household survey among 1,112 individuals aged 18 and above who were partially vaccinated (one dose) or not vaccinated at the time of the survey. Data was collected in August 2022. We collected information on participant socio-demographics, COVID-19 knowledge, prevention practices, disease history, and vaccine hesitancy. Latent class analysis was used to classify individuals into categories of vaccine hesitancy. We conducted multinomial logistic regression to test the associations between latent typologies and different demographic and COVID-19 related characteristics of study participants.ResultsUsing latent class analysis we found a four-class solution for vaccine hesitancy typologies. The identified classes were strong vaccine acceptors (30%); vaccine acceptors with some concerns (7%); vaccine sceptics (13%); and vaccine rejectors (50%). In adjusted models with vaccine sceptics as the referent group, those with high COVID-19 vaccine knowledge were significantly more likely to belong to the strong vaccine acceptors class compared to those with low vaccine knowledge (adj. RRR: 17.36, 95% CI: 10.94–27.55). Better COVID-19 prevention practices were also significantly associated with belonging to the vaccine acceptors with some concerns class than the vaccine sceptics class (adj. RRR: 2.13, 95% CI: 1.09–4.16). Those who had one dose of the COVID-19 vaccine were significantly more likely to belong in the vaccine acceptors class than the vaccine sceptics class compared to those who had no dose (adj. RRR: 6.82, 95% CI: 3.06–15.21).ConclusionsHalf of the study participants were in the vaccine rejectors class. Individuals in the vaccine sceptics and rejector classes evidenced lower vaccine knowledge and worse COVD-19 prevention practices and were less likely to have been partially vaccinated. Future program interventions should focus on improving knowledge around the vaccine, decrease rumors and misconceptions, and target individuals who may be more amenable to changing their vaccination attitudes or behaviors like vaccine sceptics or acceptors with some concerns.

The Global Burden of Absenteeism Related to COVID-19 Vaccine Side Effects Among Healthcare Workers: A Systematic Review and Meta-Analysis.

Background: A rise in absenteeism among healthcare workers (HCWs) was recorded during the COVID-19 pandemic, mostly attributed to SARS-CoV-2 infections. However, evidence suggests that COVID-19 vaccine-related side effects may have also contributed to absenteeism during this period. This study aimed to synthesize the evidence on the prevalence of absenteeism related to COVID-19 vaccine side effects among HCWs. Methods: The inclusion criteria for this review were original quantitative studies of any design, written in English, that addressed absenteeism related to the side effects of COVID-19 vaccines among HCWs. Four databases (PubMed, Scopus, Embase, and the Web of Science) were searched for eligible articles on 7 June 2024. The risk of bias was assessed using the Newcastle-Ottawa scale. Narrative synthesis and a meta-analysis were used to synthesize the evidence. Results: Nineteen observational studies with 96,786 participants were included. The pooled prevalence of absenteeism related to COVID-19 vaccine side effects was 17% (95% CI: 13-20%), while 83% (95% CI: 80-87%) of the vaccination events did not lead in any absenteeism. Study design, sex, vaccination dose, region, and vaccine type were identified as significant sources of heterogeneity. Conclusions: A non-negligible proportion of HCWs were absent from work after reporting side effects of the COVID-19 vaccine. Various demographic factors should be considered in future vaccination schedules for HCWs to potentially decrease the burden of absenteeism related to vaccine side effects. As most studies included self-reported questionnaire data, our results may be limited due to a recall bias. Other: The protocol of the study was preregistered in the PROSPERO database (CRD42024552517).

Understanding Factors Responsible for Delay and Non-Compliance in COVID-19 Vaccination at a Tertiary Care Hospital in Mumbai, India

Background: Despite extensive first-dose coverage, delays in second doses and late first doses prompted a study on vaccine hesitancy and non-compliance. Methods: In 2022, a cross-sectional survey was conducted at a Mumbai vaccination center, involving 504 individuals who had received either the first or second dose of the COVID-19 vaccine. The study, conducted from February to April 2022, included interviews using a pre-validated schedule to assess vaccine acceptance, refusal, socio-demographics, and reasons for hesitancy. Data analysis was performed using IBM SPSS Statistics software 23.0 to understand factors influencing vaccine delay and non-compliance. Result: The study interviewed 504 participants at a Mumbai vaccination center. Most were male (63.9%), aged 18-44 (80%), and skilled workers (22.6%). Of those surveyed, 64 had received only the first vaccine dose. The delay in receiving the second dose was 37.4% for BBV152 and 41% for ChAdOx1 nCoV-19. The primary reason for delay was lack of time (50.6%), followed by fear of the vaccine (14.8%). Reasons for getting vaccinated later included resolving constraints (40.5%) and compulsion (25.8%). Vaccine choice reasons varied significantly (p < 0.0005), but delay proportions were similar across vaccines (p = 0.531). Conclusion: Even after many efforts by the government, large numbers of people have not taken vaccine on time. One of the reasons, as seen in the study is a busy work schedule which has hindered timely vaccination in individuals. Making vaccine available at work place may address this issue to some extent, besides ownership of the program by the public.

Impaired SARS-CoV-2-specific responses via activated T follicular helper cells in immunocompromised kidney transplant recipients

Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+ circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination.

Myocarditis Associated with COVID-19 Vaccination.

Myocarditis after the COVID-19 vaccine is one of the important adverse events following immunization, observed mainly after mRNA-based vaccines. Importantly, post-vaccination myocarditis was less common than myocarditis after SARS-CoV-2 infection, as it was scored at 19.7 per 1,000,000 doses and 2.76 per 1000 infections. Predominantly, its course was benign and, compared with the myocarditis after COVID-19 infection, significantly fewer patients developed heart failure or died among patients with post-vaccination myocarditis. The group at highest risk of myocarditis related to COVID-19 vaccination were young males who received a second dose of an mRNA vaccine. It was observed that, among mRNA vaccines, specifically mRNA-1273 was associated with a higher risk of myocarditis. The mechanism underlying myocarditis after COVID-19 vaccination is still under investigation and certain processes are being considered. Currently, some follow-up assessments of patients who developed vaccine-induced myocarditis are available and suggest a favorable prognosis. The aim of this review is to discuss the most recent data on myocarditis after COVID-19 vaccination considering its epidemiology, clinical presentation, diagnosis, management, relative risk of myocarditis compared with SARS-CoV-2 infection, potential underlying mechanism, and follow-up data of patients who developed post-vaccination myocarditis.

Levels of high-sensitive troponin T and mid-regional pro-adrenomedullin after COVID-19 vaccination in vulnerable groups: monitoring cardiovascular safety of COVID-19 vaccination.

COVID-19 vaccines are well tolerated and effective but may have adverse effects on the cardiovascular system. Vaccine-associated myocardial injury was analysed by measuring high-sensitive troponin T (hsTnT); mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction. This was a prospective study with a vulnerable population of healthcare workers (HCWs) and elderly patients (>70 years) who were vaccinated with either one dose of ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) followed by one dose of the BNT162b2 messenger RNA vaccine (BNT), or with two doses of BNT (12th of January - 30th of November 2021). HsTnT and MR-proADM were measured in blood samples at three visits (V1: 1st immediately before vaccination; V2, 3: 3-4 weeks after 1st and 2nd vaccination). HsTnT of HCWs was compared to a healthy reference population. N = 162 volunteers were included (V1 = 161; V2, V3 = 162 each). N = 74 (45.7%) received AZ/BNT and n = 88 (54.3%) received BNT/BNT [elderly: n = 20 (12.3%), HCWs: n = 68 (42.0%)]. Median hsTnT levels were 4 ng/L, 5 ng/L and 4 ng/L (V1-V3) for AZ/BNT and at 5 ng/L, 6 ng/L and 6 ng/L (V1-V3) for BNT/BNT. Compared to the reference population (n = 300), hsTnT was significantly higher at all visits for both vaccination groups (p < 0.01), without differences between the AZ/BNT and BNT/BNT cohort. Median MR-proADM values were 0.43 nmol/L, 0.45 nmol/L, 0.44 nmol/L (V1-V3) in the AZ/BNT cohort and 0.49 nmol/L, 0.44 nmol/L, 0.47 nmol/L for BNT/BNT, respectively. Change of median hsTnT and MR-proADM between visits did not show significant increases. One HCW experienced a permanent and three a transient hsTnT increase ≥14 ng/L. No overall subtle, persistent cardiovascular involvement was observed after the 2nd COVID-19 vaccination. Elevated cardiovascular biomarkers in clinically asymptomatic individuals need further investigations.

Pertussis Outbreak During 2023 in Gipuzkoa, North Spain.

Pertussis has re-emerged in many countries despite the wide use of vaccines for over 60 years. During 2023, we observed an increase in the incidence of pertussis in Gipuzkoa, north of Spain (with a population of 657,140 inhabitants), mainly affecting children between 11 and 15 years of age. This study included all confirmed cases diagnosed by PCR in nasopharyngeal swab samples. The genome of seven isolates collected in 2023 was sequenced. Between 2018 and 2023, 884 cases of whooping cough were diagnosed. Pertussis incidence (in cases per 100,000 inhabitants) decreased from 36.7 in 2018 to no cases in 2021, increasing again to 56.8 in 2023. In 2023, the age group of 11-15 years old had the highest incidence rate of 409.3. Only 2 of the 56 children < 6 years old required hospitalization, and there were no deaths. The seven isolates collected in 2023 showed the same BPagST-4 (ptxA1/ptxP3/prn2/fim2-1/fim3-1 allelic combination), with all of them expressing the pertactin antigen. Immunity waning after the last dose of vaccination at 6 years old, together with the lack of circulation of Bordetella pertussis during the COVID-19 pandemic, were probably the main reasons for the high increase in the incidence of pertussis in Gipuzkoa in 2023.

COVID-19 Vaccine-induced antibody response to BNT162b2 mRNA in frontline healthcare workers

The emergence of SARS-CoV-2, the virus causing COVID-19, has resulted in a pandemic that has disrupted all sectors of society. Less than a year after the sequencing of the virus’s genome, emergency use authorization for the BNT162b2 vaccine was requested. The aim of this study was to evaluate the response to the BNT162b2-mRNA COVID-19 vaccine in frontline workers from two hospitals in Colombia. Nasopharyngeal swabs were collected for the molecular detection of SARS-CoV-2 using real-time PCR, and blood samples were taken to assess seroconversion using qualitative and quantitative IgA, IgG, and IgM test kits. The study was conducted at a high-complexity healthcare institution in Bucaramanga, Colombia. 245 people were included in the first round and 129 in the second. SARS-CoV-2 molecular tests were conducted by RT-qPCR, and peripheral blood samples were collected to measure IgG, IgM, and IgA. The main outcome was to establish natural infection and the antibody response induced by the vaccine. The entire population was tested at two fixed times with RT-PCR tests and antibody level measurements approximately 4 and 8 months after receiving the second vaccine dose. 62 (25.3%) and 35 (14.3%) participants had a history of positive PCR in the first and second rounds, respectively. All positive cases showed elevated levels of all immunoglobulins, especially IgG. The average concentrations of IgA, IgM, and IgG at 90 days were 1149.5 U/mL (95% CI 828.2-1470.9); 320.3 U/mL (95% CI 218.4-422.3); and 9277.3 U/mL (95% CI 8989.2-9565.3). Frontline healthcare workers showed an adequate response to the BNT162b2 mRNA vaccine.

Influencing factors of antibody response after 2 doses of inactivated COVID-19 vaccine among adults aged ≥18 years in Chongqing, China: A cross-sectional serological study.

The study aimed to explore the influencing factors after 2 doses of inactivated COVID-19 vaccines (Sinopharm/BBIBP-CorV) in the real world. We conducted a cross-sectional serological study involving 316 volunteers aged ≧ 18 years from 7 vaccination hospitals in the Yubei districts, Yuzhong districts, and Jiulongpo districts of Chongqing. Serum samples were obtained about 1 month after 2 dose vaccination, and Nabs were tested using the pseudovirus-based neutralizing assay. Chi-square or Fisher exact tests were used to analyze the seropositive rates, while the Kruskal-Wallis H or Mann-Whitney U tests were used to analyze differences in Nabs level among stratified groups. Logistic regression analyses were conducted to identify the influencing factors. The results showed that seropositive rates was 76.27% and the GMT was 26.13 (95% CI: 23.03-29.66) after 2 doses of COVID-19 inactivated vaccination. The risk of being seropositive in 18 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 to 69 years were 12.808-fold, 8.041-fold, 7.818-fold, 6.275-fold, 1.429-fold compared with the people aged ≥ 70 years (P < .05), and the risk of being seropositive of intervals 15 to 21 and 22 to 28 days were 0.273-fold and 0.286-fold compared with >28 days (P < .05), respectively. In conclusion, age may be a risk factor for reduced antibody production, and longer vaccination intervals-may be a protective factor that increases antibody production. These findings contribute to informing future vaccination strategies.

The cost of COVID-19 vaccine delivery in Bangladesh

ABSTRACT COVID-19 vaccination has been instrumental in fighting the pandemic, but evidence on the actual costs associated with delivering these vaccines in resource-constrained settings has been limited. We estimated the cost of delivering COVID-19 vaccines in Bangladesh through five delivery strategies in 2021 and 2022, including Ministry of Health (MOH) hospitals, non-MOH government hospitals, outreach at Expanded Program on Immunization (EPI) centers, mass campaigns, and schools. This was a bottom-up costing study, estimating costs from a payer and beneficiary perspective. We also mapped the funding flows for COVID-19 vaccination activities and analyzed programmatic and financial challenges. The economic cost incurred by the health system to deliver COVID-19 vaccines was $1.05 per dose, excluding vaccine costs. This was made up of a financial cost of $0.29 per dose and an opportunity cost of $0.75 per dose. School-based delivery incurred the lowest financial cost of $0.27, while outreach at EPI centers incurred the highest at $0.44 per dose. The low financial cost per dose is attributed to the high daily volumes delivered at sampled sites, minimal additional resources provided to sites to implement the COVID-19 vaccination program, and a reliance on the existing workforce. Beneficiaries spent an average of $1.63 to receive a single dose of COVID-19 vaccination at fixed sites, with transport representing the largest cost driver ($0.75 per dose). The economic cost to receive one dose of the COVID-19 vaccine was $4.78. Findings can support the Government of Bangladesh to make efficient and equitable resource allocation decisions for vaccination programs.

Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study

ABSTRACT This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3–73.3% across groups) and myalgia (36.9%; 13.3–56.7%). Unsolicited AEs were reported by 14.4% (6.7–26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7–30.0%) reported MAAEs, and 8.3% (0.0–13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.

Attitudes toward mandatory vaccination and the COVID certificate as a function of vaccination status and risk perception: A vignette‐based study

AbstractIn January 2022, several vaccination policies were debated to address the Omicron outbreak in Belgium. Considering variability in risk perception and vaccine uptake, this study aimed to understand differences in support and expectations for four scenarios, ranging from relaxed to restrictive vaccination policies, to inform policymakers. Using an online survey, 12,670 participants (46% female; Mage = 45.9, SD = 13.38) reported their risk perception, number of vaccination doses (0/1, 2, 3 doses) as well as their support and several anticipated psychological outcomes for each scenario. Mixed model ANCOVA showed a pattern of preferential support for the relaxed scenario and more positive anticipated outcomes (general well‐being and government appraisals) compared to the restrictive policies, that were treated equivalently. An exception to this pattern was found when people were vaccinated with three doses and perceived high risk. Taken separately, risk perception and vaccination status were not sufficient to drive positive attitudes toward restrictive policies; only their interaction had an effect. Limitations include the self‐selected sample and the vignette methodology. The conjunct role of risk perception and vaccination status should be considered when discussing the introduction of restrictive vaccination policies. These findings inform vaccination strategies management during pandemics.

Abstract PR-07: Optimally designed mRNA vaccine encoding tumor-specific antigens identified in a colorectal cancer model leads to complete tumor rejection in mice

Abstract mRNA vaccines can be designed to encode multiple epitopes of choice, which is a crucial advantage when aiming to include a broad coverage immune response. Upon translation, the cell machinery must process the vaccine-encoded poly-epitope protein to release individual peptides. This processing step is key in inducing an immune response toward selected epitopes, as efficient processing yields a higher amount of peptide available for MHC-I presentation. The efficiency of peptide processing is greatly influenced by the peptide surrounding context (i.e. the flanking amino acids in N-and C-terminal). Aberrantly expressed tumor-specific antigens (aeTSAs) are MHC-I-associated peptides (MAPs) resulting from cancer-specific epigenetic changes and splicing aberrations. In contrast to TSAs derived from mutated protein-coding exons, aeTSAs are highly shared by different tumors. Moreover, unlike commonly used tumor-associated antigens (TAAs), they are not expressed by normal healthy cells, which is pivotal for inducing strong CD8+ T cell responses. The present study aimed to determine whether RNA vaccines encoding aeTSAs would elicit protective anti-tumor responses against a colorectal cancer cell line model (MC38). We hypothesized that multiepitope mRNA vaccine efficacy would be improved if the mRNA construct was composed of minimal epitopes (here, cancer antigens) bordered by optimal (rather than natural) flanking sequences. Thus, we designed 2 vaccine constructs encoding 5 aeTSAs identified by mass spectrometry in MC38 tumor cells. The 2 constructs differ in the identity of the amino acids flanking the antigens (natural vs. substituted antigen flanking sequences). Mice were injected subcutaneously with MC38 cells on Day 0. Three mRNA vaccine doses were administered intravenously one week apart, starting at Day 4. Vaccination with our improved mRNA vaccine design showed a clear therapeutic effect. As opposed to the natural flanking sequences design resulting in delayed tumor growth, vaccination with the substituted flanking sequences design led to the complete elimination of tumors and the survival of all mice. Elispot and dextramer stainings revealed that at least 3 of the 5 MC38 aeTSAs were immunogenic and that the amplitude of antigen-specific CD8+ T cell responses was significantly higher in mice vaccinated with the substituted flanking sequences design. Our results confirm our hypothesis that highly proficient flanking regions have intrinsic benefits that can be carried over to different antigens. From a translational perspective, our work provides new insights into the therapeutic potential of optimally designed aeTSA-encoding mRNA vaccines for treating cancers. Citation Format: Marie-Pierre Hardy, Krystel Vincent, Gabriel Ouellet-Lavallée, Chantal Durette, Isabelle Caron, Joel Lanoix, Mathieu Courcelles, Jean-Philippe Laverdure, Pierre Thibault, Claude Perreault. Optimally designed mRNA vaccine encoding tumor-specific antigens identified in a colorectal cancer model leads to complete tumor rejection in mice [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr PR-07.

Tixagevimab–cilgavimab for preventing breakthrough COVID-19 in dialysis patients: a prospective study

Abstract Background The effectiveness of tixagevimab–cilgavimab as pre-exposure prophylaxis (PrEP) against breakthrough coronavirus disease 2019 (COVID-19) in dialysis patients remains uncertain due to limited data. Methods In this multicenter prospective study, we enrolled vaccinated dialysis patients and divided them into two groups: tixagevimab–cilgavimab group (received a 150 mg/150 mg intramuscular dose of tixagevimab–cilgavimab) and control group (age-matched patients not receiving tixagevimab–cilgavimab). The primary outcome was the breakthrough COVID-19 rate at six months, whereas secondary outcomes included COVID-19-related hospitalization, ICU admission, endotracheal intubation, and mortality. The safety of tixagevimab–cilgavimab was assessed. Results Two hundred participants were enrolled, with equal numbers in each group (n = 100 each). Baseline characteristics were comparable between groups, except for a higher number of COVID-19 vaccine doses in the tixagevimab–cilgavimab group (median [IQR]: 4 [3–5] vs. 3 [3, 4]; P = 0.01). At six months, the breakthrough COVID-19 rates were comparable between the tixagevimab–cilgavimab (17%) and control (15%) groups (P = 0.66). However, the median (IQR) time to diagnosis of breakthrough infections tended to be longer in the tixagevimab–cilgavimab group (4.49 [2.81–4.98] vs. 1.96 [1.65–2.91] months; P = 0.08). Tixagevimab–cilgavimab significantly reduced COVID-19-related hospitalization rates (5.9% vs. 40.0%; P = 0.02) among participants with breakthrough infections. All tixagevimab–cilgavimab-related adverse events were mild. Conclusion The use of tixagevimab–cilgavimab as PrEP in vaccinated dialysis patients during the Omicron surge did not prevent breakthrough infections but significantly reduced COVID-19-related hospitalizations. Further research should prioritize alternative strategies.

Impact of COVID-19 Vaccination on Female Fertility.

Despite evidence in previous literature regarding vaccine safety, more data were needed as concerns about COVID-19 vaccines were raised, particularly regarding their effects on female fertility, exacerbated by the widespread dissemination of information without scientific evidence. This study aims to answer the question: does COVID-19 vaccination have any impact on female fertility at a population level. In this ecological study, vaccination rates against COVID-19 and birth rates in 100 different countries were correlated. In addition, the correlation between these two rates of interest and the Gini index were also analyzed. Data were retrieved from the World Population Prospects document produced by the Population Division of the United Nations Department of Economic and Social Affairs, from the World Health Organization (WHO) website, and from the World Bank website. Statistical analyses were conducted using the ANOVA test, and Pearson's correlation using the JASP software. For all analyses, results were considered significant if P < 0.05. In evaluating the trend of the birth rate in the countries included in the study, a persistent reduction of approximately 1.66% per year was observed between 2010 and 2022. From 2019 to 2022, the decline was close to 5%, resulting in an annual average reduction of 1.68%, which is similar to previous years. Among the selected countries, until December 2021, the average number of vaccine doses administered was 137 per 100 inhabitants. There was no observed correlation between the number of vaccine doses administered in different countries and the variation in the birth rate per thousand inhabitants between 2019 and 2022 (Pearson's r = 0.075; P = 0.455). A correlation was found between the Gini index and the birth rate, considering the base year of 2022, with a Pearson's r value of 0.376 (P < 0.01). This correlation remained consistent for all other years. A negative correlation was found between vaccine doses and the Gini index, with a Pearson's r value of -0.219 (P = 0.040). The findings of this article, as well as previous scientific evidence, do not identify any correlation between COVID-19 vaccines and female fertility issues. The associations analyzed in this study indicate the safety of vaccines for reproductive health and contribute to reducing vaccine hesitancy among the population of childbearing age.

Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2023-24 School Year.

In the United States, states and local jurisdictions set vaccination requirements for school attendance, conditions and procedures for exemptions from these requirements, grace periods for submitting documentation, and provisional enrollment for students who need more time to be vaccinated. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. Data reported by 49 states and the District of Columbia (DC) for the 2023-24 school year were used for national- and state-level estimates of the following measures: complete vaccination with required doses of measles, mumps, and rubella vaccine (MMR), diphtheria, tetanus, and acellular pertussis vaccine (DTaP), poliovirus vaccine (polio), and varicella vaccine (VAR); exemptions from vaccination; and school attendance while meeting requirements. The 2023-24 kindergarten class became age-eligible to complete most state-required vaccinations during the COVID-19 pandemic, after schools had returned to routine in-person learning. Compared with approximated national coverage levels across all reported vaccines for the 2019-20 (95%) and 2022-23 (93%) school years, coverage dropped below 93% for the 2023-24 school year, ranging from 92.3% for DTaP to 92.7% for MMR. Exemptions increased to 3.3%, compared with those during the 2022-23 (3.0%) and 2021-22 school years (2.6%). Coverage with MMR, DTaP, polio, and VAR decreased in 35, 32, 33, and 36 jurisdictions, respectively, compared with the 2022-23 school year. Exemptions increased in 41 jurisdictions, with 14 reporting that >5% of kindergartners had an exemption from one or more vaccine. Efforts by health departments, schools, and providers are needed to ensure that students begin school fully vaccinated.

Drivers of COVID-19 vaccine uptake among rural populations in Madagascar: a cross-sectional study

BackgroundThe WHO set the global immunisation threshold for COVID-19 at 70% to achieve worldwide protection against the disease. To date, global COVID-19 vaccine coverage is still below this threshold, in particular in several sub-Saharan African (SSA) countries, such as Madagascar. While factors influencing COVID-19 vaccine hesitancy have been widely explored in the past few years, research on drivers of COVID-19 vaccine uptake remains scarce. This study aimed at investigating drivers associated with COVID-19 vaccine uptake in the Boeny region of Madagascar.MethodsThe study used a cross-sectional survey design to collect data on drivers of vaccine uptake from a sample of adults recruited from 12 healthcare facilities between November 2022 and February 2023. Relative and absolute frequencies were used to summarize participants’ characteristics. Prevalence ratios were estimated by Poisson regression to identify and compare sociodemographic and motivational drivers of vaccine uptake among those who were willing to get vaccinated against COVID-19 with those who had already been vaccinated.ResultsA total of 928 participants aged between 18 and 76 years were included in the study. Among those recruited, 44.9% (n = 417) had already been vaccinated and 55.1% (n = 511) were willing to receive their first dose of COVID-19 vaccine on the day of the interview. The proportions of those respondents who live in urban areas (56.5% vs. 43.8%) and who have high school or university education (46.6% vs. 35.8%) were higher for the uptake group, whereas the proportion of employed respondents (66.3% vs. 56.5%) was higher among those willing to get vaccinated. Vaccine being free of charge (aPR = 1.77 [CI 95%: 1.45–2.17]) and being able to travel again (aPR = 1.61 [CI 95%: 1.30–1.98]) were the drivers most strongly associated with higher vaccine uptake after adjustment for sociodemographic factors.ConclusionsThis study shows that actual COVID-19 vaccine uptake is influenced by a different set of factors than willingness to get vaccinated. Taking this difference in drivers into account can inform more tailored vaccination strategies to increase worldwide coverage.