Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

<p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p

Factors associated with US caregivers uptake of pediatric COVID-19 vaccine by race and ethnicity.

OBJECTIVES: To assess differences in willingness to vaccinate children against COVID-19, and factors that may be associated with increased acceptance, among US caregivers of various racial and ethnic identities who presented with their child to the Emergency Department (ED) after emergency use authorization of vaccines for children ages 5-11. STUDY DESIGN: A multicenter, cross-sectional survey of caregivers presenting to 11 pediatric EDs in the United States in November-December 2021. Caregivers were asked about their identified race and ethnicity and if they planned to vaccinate their child. We collected demographic data and inquired about caregiver concerns related to COVID-19. We compared responses by race/ethnicity. Multivariable logistic regression models served to determine factors that were independently associated with increased vaccine acceptance overall and among racial/ethnic groups. RESULTS: Among 1916 caregivers responding, 54.67% planned to vaccinate their child against COVID-19. Large differences in acceptance were noted by race/ethnicity, with highest acceptance among Asian caregivers (61.1%) and those who did not specify a listed racial identity (61.1%); caregivers identifying as Black (44.7%) or Multi-racial (44.4%) had lower acceptance rates. Factors associated with intent to vaccinate differed by racial/ethnic group, and included caregiver COVID-19 vaccine receipt (all groups), caregiver concerns about COVID-19 (White caregivers), and having a trusted primary provider (Black caregivers). CONCLUSIONS: Caregiver intent to vaccinate children against COVID-19 varied by race/ethnicity, but race/ethnicity did not independently account for these differences. Caregiver COVID-19 vaccination status, concerns about COVID-19, and presence of a trusted primary provider are important in vaccination decisions

A multicenter evaluation of pediatric emergency department injury visits during the COVID-19 pandemic.

BACKGROUND: Injuries, the leading cause of death in children 1-17&nbsp;years old, are often preventable. Injury patterns are impacted by changes in the childs environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. METHODS: This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children &lt; 18&nbsp;years old. Injury was defined by at least one International Classification of Disease-10th revision (ICD-10) code for bodily injury (S00-T78). The main study outcomes were total and proportion of PED injury-related visits compared to all visits in March through December 2020 and to the same months in 2019. Weekly injury visits as a percentage of total PED visits were calculated for all weeks between January 2019 and December 2020. RESULTS: The study included 741,418 PED visits for injuries pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020). Overall PED visits from all causes decreased 27.4% in March to December 2020 compared to the same time frame in 2019; however, the proportion of injury-related PED visits in 2020 increased by 37.7%. In 2020, injured children were younger (median age 6.31&nbsp;years vs 7.31 in 2019), more commonly White (54% vs 50%, p &lt; 0.001), non-Hispanic (72% vs 69%, p &lt; 0.001) and had private insurance (35% vs 32%, p &lt; 0.001). Injury hospitalizations increased 2.2% (p &lt; 0.001) and deaths increased 0.03% (p &lt; 0.001) in 2020 compared to 2019. Mean injury severity score increased (2.2 to 2.4, p &lt; 0.001) between 2019 and 2020. Injuries declined for struck by/against (- 4.9%) and overexertion (- 1.2%) mechanisms. Injuries proportionally increased for pedal cycles (2.8%), cut/pierce (1.5%), motor vehicle occupant (0.9%), other transportation (0.6%), fire/burn (0.5%) and firearms (0.3%) compared to all injuries in 2020 versus 2019. CONCLUSIONS: The proportion of PED injury-related visits in March through December 2020 increased compared to the same months in 2019. Racial and payor differences were noted. Mechanisms of injury seen in the PED during 2020 changed compared to 2019, and this can inform injury prevention initiatives

Should COVID-19 vaccines be mandated in schools? - An international caregiver perspective

Objectives: Caregiver attitudes toward mandating COVID-19 vaccines for their children are poorly understood. We aimed to determine caregiver acceptability of COVID-19 vaccine mandates for schools/daycares and assess if opposition to mandates would result in removal of children from the educational system. Study design: Perform a cross-sectional, anonymous survey of adult caregivers with children ≤ 18 years presenting to 21 pediatric emergency departments in the United States, Canada, Israel, and Switzerland, November 1st through December 31st, 2021. The primary outcome was caregiver acceptance rates for school vaccine mandates, and the secondary outcomes included factors associated with mandate acceptance and caregiver intention to remove the child from school. Results: Of 4,393 completed surveys, 37% of caregivers were opposed to any school vaccine mandate. Caregiver acceptance was lowest for daycare settings (33%) and increased as the child\u27s level of education increased, college (55%). 26% of caregivers report a high likelihood (score of 8-10 on 0-10 scale) to remove their child from school if the vaccine became mandatory. Child safety was caregivers\u27 greatest concern over vaccine mandates. A multivariable model demonstrated intent to vaccinate their child for COVID-19 (OR = 8.9, 95% CI 7.3 to 10.8; P \u3c 0.001) and prior COVID-19 vaccination for the caregiver (OR = 3.8, 95% CI 3.0 to 4.9; P \u3c 0.001) had the greatest odds of increasing mandate acceptance for any school level. Conclusions: Many caregivers are resistant to COVID-19 vaccine mandates for schools, and acceptance varies with school level. One-fourth of caregivers plan to remove their child from the educational system if vaccines become mandated