Human Vaccines & Immunotherapeutics最新文献

Patients on dialysis (PoD) are at high risk of severe morbidity and mortality from COVID-19. Characterizing long-term vaccine immune responses in these patients will help optimize vaccine schedule for PoD. This study aimed to determine whether long-term humoral and B and T cell-responses post 3^rd and 4^th dose of the BNT162b2 vaccine differed between PoD and controls. Non-infected PoD and controls vaccinated with BNT162b2 were recruited in Ziv Medical Center, Israel, between 2021 and 2022. Specimens were collected 1-2 months pre 3^rd dose; 1-3 months post 3^rd dose; 4-5 months post 3^rd dose and 3-5 months post the 4^th dose. Anti-SARS-CoV-2 spike (spike) specific antibodies, spike specific memory B cells, and spike specific CD154+ T cells as well as cytokines producing CD4+/CD8+ T cells were measured using standardized assays and compared between PoD and controls at each time point using Mann Whitney and Fisher's exact tests. We recruited 22 PoD and 20 controls. Antibody levels in PoD were lower compared to controls pre 3^rd dose but not post 3^rd and 4^th doses. Frequencies of spike specific memory B cell populations were similar between PoD and controls overall. Frequencies of spike specific T cells, including those producing IFNγ and TNFα, were not lower in PoD. B and T cell mediated immune response in PoD following a 3^rd and a 4^th dose of the BNT162b2 vaccine was not inferior to controls up to 5 months post vaccination. Our results suggest that standard BNT162b2 vaccination is suitable for this group.

Messenger ribonucleic acid (mRNA) technology has been rapidly applied for the development of the COVID-19 vaccine. However, naked mRNA itself is inherently unstable. Lipid nanoparticles (LNPs) protect mRNAs from extracellular ribonucleases and facilitate mRNA trafficking. For mRNA vaccines, antigen-presenting cells utilize LNPs through uptake to elicit antigen-specific immunity. There are reports on the impact of various physical characteristics of LNPs, particularly those with sizes less than 200 nm, especially 50 to 150 nm, on the overall stability and protective efficacy of mRNA vaccines. To address this, a single change in the size of LNPs using the same mRNA stock solution was assessed for the physicochemical characterization of the resulting mRNA-LNPs vaccine, along with the evaluation of their protective efficacy. Particles of smaller sizes generally disperse more effectively in solutions, with minimized occurrence of particle precipitation and aggregation. Here, we demonstrate that the vaccine containing 80-100 nm mRNA-LNPs showed the best stability and protection at 4°C and -20°C. Furthermore, we can conclude that freezing the vaccine at -20°C is more appropriate for maintaining stability over the long term. This effort is poised to provide a scientific basis for improving the quality of ongoing mRNA vaccine endeavors and providing information on the development of novel products.

A wide range of survey studies have explored vaccination hesitancy/resistance during the COVID-19 pandemic and provided evidence that this can be explained by several individual variables from the ideological, clinical, and socio-affective domain. However, evidence about which individual variables predict vaccine hesitancy in the post-pandemic state of COVID-19 is meager. We administered a battery of questionnaires to a group of 120 Italian participants with high and low scores on the adult vaccine hesitancy scale (aVHS) to investigate the predictive role of ideological (i.e. political orientation), clinical (i.e. anxiety, interoceptive accuracy), and socio-affective (i.e. alexithymia, disgust sensitivity/propensity, empathy) variables on vaccine hesitancy/resistance. This study provides evidence that lower interoceptive awareness and cognitive empathy are predictors of a greater hesitancy to get vaccinated in the post-pandemic COVID-19 state.

ER+ breast cancers (BC) are characterized by the elevated expression and signaling of estrogen receptor alpha (ESR1), which renders them sensitive to anti-endocrine therapy. While these therapies are clinically effective, prolonged treatment inevitably results in therapeutic resistance, which can occur through the emergence of gain-of-function mutations in ESR1. The central importance of ESR1 and development of mutated forms of ESR1 suggest that vaccines targeting these proteins could potentially be effective in preventing or treating endocrine resistance. To explore the potential of this approach, we developed several recombinant vaccines encoding different mutant forms of ESR1 (ESR1mut) and validated their ability to elicit ESR1-specific T cell responses. We then developed novel ESR1mut-expressing murine mammary cancer models to test the anti-tumor potential of ESR1mut vaccines. We found that these vaccines could suppress tumor growth, ESR1mut expression and estrogen signaling in vivo. To illustrate the applicability of these findings, we utilize HPLC to demonstrate the presentation of ESR1 and ESR1mut peptides on human ER+ BC cell MHC complexes. We then show the presence of human T cells reactive to ESR1mut epitopes in an ER+ BC patient. These findings support the development of ESR1mut vaccines, which we are testing in a Phase I clinical trial.

The World Health Organization recommends tetanus toxoid immunization before or during pregnancy for all women of childbearing age. The goal is to reduce maternal and neonatal mortality due to tetanus. According to the 2016 Ethiopia Demographic and Health Survey (EDHS) report, more than half (51%) of women did not receive protective doses of tetanus immunization. To the best of our knowledge, this study uniquely tried to assess the level of protective doses of tetanus toxoid immunization in southern Ethiopia. A community-based cross-sectional study was conducted among 580 randomly selected participants. Variable with p-value of less than .25 in the bivariate analysis were included in the multivariable logistic regression analysis. Finally, statistical significance was declared at a p-value of less than .05. The proportion of protective doses of tetanus toxoid immunization uptake in the area was found to be 41.9% (95% CI: 38-46%). Being enrolled in formal education [AOR = 6.55, 95% CI: 3.23-9.01], having at least two postnatal care visits [AOR = 3.82; 95% CI: 1.78-6.40], having at least four antenatal care visits [AOR = 2.56; 95% CI: 1.41-4.34], and being visited by Health Extension Workers [AOR = 2.66; 95% CI: 1.42-4.01] were found to be factors enhancing the uptake of protective doses of tetanus toxoid immunization. Generally, the uptake or prevalence of the protective doses of tetanus toxoid immunization in the area was lower than the World Health Organization's target. Therefore, all responsible bodies, including healthcare providers, need to strengthen counseling mothers to enhance the uptake of tetanus toxoid immunization.

Although COVID-19 vaccine uptake was high in Quebec for the primary series, vaccine acceptance decreased for the subsequent booster doses. This article presents the evolution of vaccine intention, self-reported vaccination behaviors, and vaccine hesitancy over 2 years. A series of cross-sectional surveys were conducted in Quebec between March 2020 and March 2023, with a representative sample of 3,330 adults recruited biweekly via a Web panel. Panelists could have answered multiple times over the course of the project. A cohort of respondents was created to assess how attitudes and behaviors about COVID-19 vaccines evolved. Descriptive statistics and multivariate logistic regressions were performed. Among the 1,914 individuals with no or low intention of getting vaccinated in Fall 2021 (Period 1), 1,476 (77%) reported having received at least two doses in the Winter 2023 (Period 2). Not believing in conspiracy theory (OR = 2.08, 95% CI: 1.65-2.64), being worried about catching COVID-19 (OR = 2.12, 95% CI: 1.65-2.73) and not living in a rural area (ORs of other areas are 2.27, 95% CI: 1.58-3.28; 1.66, 95% CI: 1.23-2.26; 1.82 95% CI: 1.23-2.73) were the three main factors associated with being vaccinated at Period 2. Among the 11,117 individuals not hesitant at Period 1, 1,335 (12%) became hesitant at Period 2. The three main factors significantly associated with becoming vaccine hesitant were the adherence to conspiracy theories (OR = 2.28, 95% CI: 1.95-2.66), being a female (OR = 1.67, 95% CI: 1.48-1.90) and being younger than 65 years old (the ORs for 18-34, 35-49, and 50-64 compared with 65 and over are 2.82, 95% CI: 2.32-3.44; 2.39, 95% CI: 2.00-2.86 and 1.82, 95% CI: 1.55-2.15 respectively). As the pandemic is over, monitoring the evolution of vaccine attitudes and uptake will be important.

There is a continued need for research to better understand the influence social media has on parental vaccination attitudes and behaviors, especially research capturing the effects of the COVID-19 pandemic. The goal of this study was to explore parents' perspectives related to the impact the pandemic had on 1) social media engagement, 2) vaccine messaging on social media, and 3) factors to guide future intervention development. Between February and March 2022, 6 online, synchronous, text-based focus groups were conducted with parents of adolescents aged 11 to 17 years. Participants who all utilized social media were recruited from across the United States. Qualitative data were analyzed using content analysis. A total of 64 parents participated. Average age was 47 years, and participants were predominantly White (71.9%), female (84.3%), and engaged with social media multiple times per day (51.6%). Participants (95.3%) viewed obtaining all recommended vaccines as important or very important; however, overall vaccination rates for their adolescents were varied (50% ≥1 dose HPV; 59.4% MenACWY; 78.1% Tdap; 65.6% Flu; 81.3% COVID-19). Three themes emerged highlighting the pandemic's impact on parent's (1) general patterns of social media use, (2) engagement about vaccines on social media and off-line behaviors related to vaccination, and (3) perspectives for developing a credible and trustworthy social media intervention about vaccination. Participants reported fatigue from contentious vaccine-related content on social media and desired future messaging to be from recognizable health institutions/associations with links to reputable resources. Plus, providers should continue to provide strong vaccine recommendations in clinic.

We sought in-depth understanding on the evolution of factors influencing COVID-19 booster dose and bivalent vaccine hesitancy in a longitudinal semi-structured interview-based qualitative study. Serial interviews were conducted between July 25th and September 1^st, 2022 (Phase I: univalent booster dose availability), and between November 21^st, 2022 and January 11^th, 2023 (Phase II: bivalent vaccine availability). Adults (≥18 years) in Canada who had received an initial primary series and had not received a COVID-19 booster dose were eligible for Phase I, and subsequently invited to participate in Phase II. Twenty-two of twenty-three (96%) participants completed interviews for both phases (45 interviews). Nearly half of participants identified as a woman (n = 11), the median age was 37 years (interquartile range: 32-48), and most participants were employed full-time (n = 12); no participant reported needing to vaccinate (with a primary series) for their workplace. No participant reported having received a COVID-19 booster dose at the time of their interview in Phase II. Three themes relating to the development of hesitancy toward continued vaccination against COVID-19 were identified: 1) effectiveness (frequency concerns; infection despite vaccination); 2) necessity (less threatening, low urgency, alternate protective measures); and 3) information (need for data, contradiction and confusion, lack of trust, decreased motivation). The data from interviews with individuals who had not received a COVID-19 booster dose or bivalent vaccine despite having received a primary series of COVID-19 vaccines highlights actionable targets to address vaccine hesitancy and improve public health literacy.

Herpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi‑country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.