Global Health Commodities Supply Chain in the Era of COVID-19 Pandemic: Challenges, Impacts, and Prospects: A Systematic Review.

Background: The COVID-19 pandemic led to the most substantial health crisis in the 21st Century. This pandemic interrupted the supply of essential commodities for human beings. Among the essential commodities for human survival, disruption of the supply of essential health commodities has become a global concern. Objective: The study aimed to systematically analyze published articles on the challenges, impacts, and prospects of the global health commodities' supply chain in the era of the COVID-19 pandemic. Methods: A standard searching strategy was conducted in seven research databases to retrieve pertinent articles. Finally, 459 articles were retrieved for further screening, and only 13 articles were selected for final synthesis. Results: Almost 38.5% of the studies targeted the supply chain of health commodities used to treat HIV, TB, and malaria. Lockdown policies, travel restrictions, lack of transportation, low manufacturing capacity, and rising costs were the significant challenges indicated for the supply interruption of essential health commodities and COVID-19 vaccines. Findings indicated that the supply interruption of essential health commodities leads to a devastating impact on global health. Conclusion: Global medicine shortages due to the pandemic crisis can have a devastatingly harmful impact on patient outcomes and might result in a devastatingly long-lasting effect on the health of the world community. Supply-related challenges of the COVID-19 vaccine affect countries' ambitions for achieving herd immunity quickly. Monitoring the pandemic's effect on the health commodities' supply system and designing a short-term and long-term resilient health supply chain system that can cope with current and future health catastrophes is pivotal.

Factors influencing Thai university students' decisions to take COVID-19 vaccine booster doses: a cross-sectional survey.

BACKGROUND: We aimed to describe the acceptance of COVID-19 vaccine booster doses and factors influencing this among Thai university students. METHODS: A cross-sectional survey was conducted between July and September 2022. All university students in Thailand were eligible to participate. We explored the acceptance rate of COVID-19 vaccine booster doses and regular vaccines (if available) among university students. Associations between factors influencing the acceptance of vaccination were analyzed by multiple logistic regression analysis. RESULTS: A total of 322 participants were surveyed (78.9% female, age 18 to 49 years (mean = 22.6, standard deviation = 5.47)). Most participants (85.7%) were undergraduate students (Bachelor level), and a proportion (84.8%) had a background in health sciences studies. The proportions who accepted booster doses and regular vaccines were 52.8% and 69.3%, respectively. Vaccine accessibility was found to be significantly associated with the acceptance of booster doses (adjusted odds ratio (AOR) = 2.77, 95% confidence interval (CI) = 1.10-6.97), while the availability of scientific evidence (AOR = 3.44, 95% CI = 1.21-9.77) was significantly associated with the acceptance of regular vaccines. CONCLUSIONS: This study contributes to addressing the knowledge gap regarding acceptance of COVID-19 vaccine booster doses among university students in Thailand. Our findings revealed that vaccine accessibility and the availability of scientific evidence, as well as vaccination costs, influenced individuals' decisions around accepting vaccine booster doses. Further research should focus on the dynamics of vaccine acceptance to facilitate the development of targeted strategies and support vaccination policymaking in Thailand.

Pfizer COVID19 vaccine is not associated with acute cardiovascular events excluding myocarditis- a national self-controlled case series study.

BACKGROUND: Despite publications assuring no increased risk for acute cardiovascular events (excluding myocarditis) and sudden death following administration of COVID19 vaccines, these issues still stir much public ado. We assessed the risk for acute cardiovascular events that require hospitalization (excluding myocarditis) and for mortality in the short-term following administration of the second dose of the Pfizer COVID19 vaccine in Israel. METHODS: Using a self-controlled case series (SCCS) study design and national databases, all second-dose vaccinees, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction/acute stroke/acute thromboembolic event) that required hospitalization in the 60 days following vaccine administration between Jan 11th, 2021 and Oct 31st 2021, were included. A similar analysis was carried out for mortality. The first 30 days following vaccination were defined as risk period while the next 30 days were defined as control period. The probability for an event between these periods was compared using a conditional logistic regression model, accounting for sex, age group, background morbidity and seasonal risk. RESULTS: Out of 5,700,112  second dose vaccinees, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration. Following exclusion of 106 due to technical considerations, 1,979 events occurred during the risk period and 2,078 during the control period: Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90-1.01, p = 0.12. Adjusted OR was similar (OR = 0.88, 95%CI 0.72-1.08). Stratifying by age showed no increased risk in any age group. Mortality assessment indicated low number of events in both periods. These results were consistent in sensitivity analyses. CONCLUSIONS: There was no increased risk for acute cardiovascular events (excluding myocarditis) in the risk period compared to the control period following administration of the second dose of Pfizer COVID19 vaccine. Mortality data raised no concerns either, but may have been biased.

Survival and safety analysis of COVID-19 vaccine in Chinese patients with non-small cell lung cancer.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused a worldwide challenging and threatening pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccines in Non-Small Cell Lung Cancer (NSCLC) patients. METHODS: Patient self-reported adverse events related to vaccines were recorded by follow-up through a uniform questionnaire. Survival analysis was performed by Kaplan-Meier method. A multivariate analysis was performed by the Cox proportional hazard regression model to determine the effect of each variable on the survival of lung cancer patients. RESULTS: A total of 860 patients with NSCLC on treatment were enrolled. Mean age was 57 years in patients with early stage group and 62 years in advanced stage group. The vaccination rate was 71.11% for early-stage patients and 19.48% for advanced-stage patients; most of them (86.5%) received the COVID-19 inactivated virus (Vero cell) vaccine (Coronavac; Sinovac). The most common systemic adverse reaction was weakness. The main reason for vaccine refusal in those unvaccinated patients was concern about the safety of vaccination in the presence of a tumor and undergoing treatment (56.9% and 53.4%). The 1-year disease-free survival (DFS) rate was 100% for vaccinated and 97.4% for unvaccinated early-stage patients. Then we compared the progression-free survival (PFS) of vaccinated (median PFS 9.0 months) and unvaccinated (median PFS 7.0 months) advanced stage patients (p = 0.815). Advanced NSCLC patients continued to be divided into groups receiving radio-chemotherapy, immunotherapy, and targeted therapy, with no statistical difference in PFS between the groups (p > 0.05). The median overall survival (OS) of vaccinated patients was 20.5 months, and that of unvaccinated patients was 19.0 months (p = 0.478) in advanced NSCLC patients. CONCLUSIONS: COVID-19 vaccination is safe for Chinese NSCLC patients actively receiving different antitumor treatments without increasing the incidence of adverse reactions, and vaccination does not affect cancer patient survival.

Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients.

OBJECTIVE: Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19. STUDY DESIGN AND SETTING: A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (n = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19. RESULTS: Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, n = 462; unvaccinated, n = 20,998); tri-dose cohort (vaccinated, n = 517; unvaccinated, n = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, p < 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, p > 0.05). CONCLUSION: In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.

COVID-19 vaccine uptake among children and adolescents in Norway: A comprehensive registry-based cohort study of over 800,000 individuals.

Factors related with COVID-19 vaccine uptake in children and adolescents in Norway remain unclear, despite this being useful knowledge for future pandemic preparedness. This study aimed to comprehensively examine individual and familial factors associated with vaccine uptake in children and adolescents in Norway. We utilized nationwide registry-data from various health registries and Statistics Norway, encompassing all children and adolescents living in Norway during the pandemic, until 31-Dec-2022. Vaccine uptake is defined as receiving at least one dose of COVID-19 vaccine. We employed a forward stepwise logistic regression model and a random forest machine-learning algorithm to explore the relationship between vaccine uptake and socio-cultural, demographic, and health-related factors. We included 423,548 5-11-year-olds, 269,830 12-15-year-olds, and 120,854 16-17-year-olds. Vaccine uptake in these three groups was respectively 2.6 %, 73.3 %, and 87.3 %. Factors associated with vaccine uptake varied by age group. In youngest children, immigrant background (Odds-ratio (OR) = 1.58, 95 % confidence interval (CI) (1.14-2.19)), born extremely preterm (OR = 2.38, 95 % CI (1.60-3.54)), having risk of severe COVID-19 (OR = 5.40, 95 % CI (4.69-6.23) and maternal COVID-19 vaccination (OR = 6.34, 95 % CI (5.35-7.53)) were positively associated with vaccine uptake. The latter two factors were also strongly, positively associated with vaccine uptake in 12-15-year-olds, while previous SARS-CoV-2 infection was negatively associated (OR = 0.12, 95 % CI (0.11-0.14). Similar findings were observed in 16-17-year-olds. COVID-19 vaccine uptake differed markedly by age group, and major associated factors included socio-demographics and parental COVID-19 vaccination status, prior SARS-CoV-2 infection, but also being born premature and having moderate or high risk of severe COVID-19.

Poor durability of the neutralizing response against XBB sublineages after a bivalent mRNA COVID-19 booster dose in persons with HIV.

We estimated the dynamics of the neutralizing response against XBB sublineages and T cell response in persons with HIV (PWH) with previous AIDS and/or CD4 < 200/mm3 receiving the bivalent original strain/BA.4-5 booster dose in fall 2022. Samples were collected before the shot (Day 0), 15 days, 3, and 6 months after. PWH were stratified by immunization status: hybrid immunity (HI; vaccination plus COVID-19) versus nonhybrid immunity (nHI; vaccination only). Fifteen days after the booster, 16% and 30% of PWH were nonresponders in terms of anti-XBB.1.16 or anti-EG.5.1 nAbs, respectively. Three months after, a significant waning of anti-XBB.1.16, EG.5.1 and -XBB.1 nAbs was observed both in HI and nHI but nAbs in HI were higher than in nHI. Six months after both HI and nHI individuals displayed low mean levels of anti-XBB.1.16 and EG.5.1 nAbs. Regarding T cell response, IFN-γ values were stable over time and similar in HI and nHI. Our data showed that in PWH, during the prevalent circulation of the XBB.1.16, EG.5.1, and other XBB sublineages, a mRNA bivalent vaccine might not confer broad protection against them. With a view to the 2023/2024 vaccination campaign, the use of the monovalent XBB.1.5 mRNA vaccine should be urgently warranted in PWH to provide adequate protection.

Risk of Corneal Transplant Rejection Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

INTRODUCTION: The COVID-19 pandemic has initiated an unparalleled global vaccination campaign, raising concerns about the vaccine's effects on various health conditions, including the risk of corneal transplant rejection. This systematic review aimed to identify the relationship between COVID-19 vaccination and rejection of corneal transplant, filling a significant gap in the existing medical literature. METHODS: A literature search was performed across multiple databases up to February 12, 2024, to identify studies evaluating the risk of corneal transplant rejection post-COVID-19 vaccination. Eligible studies were original research that reported outcomes of corneal graft rejection following vaccination. Nested Knowledge web software facilitated screening and data extraction. The Newcastle-Ottawa Scale was employed for quality assessment. A meta-analysis was conducted to calculate the aggregated relative risk (RR) utilizing R software version 4.3. RESULTS: Six studies were included in the qualitative synthesis, with four meeting the criteria for meta-analysis. These studies varied in geographic location, surgical techniques, and types of vaccines used. The pooled RR for corneal transplant rejection following COVID-19 vaccination was 0.816 (95% CI 0.178-1.453), indicating no significant risk of rejection. No statistical heterogeneity was observed among the studies (I2 = 0%). CONCLUSIONS: This review and meta-analysis found no significant evidence that COVID-19 vaccination increases the risk of corneal graft rejection. However, the current evidence is insufficient to conclusively determine the vaccine's safety for corneal transplant recipients. These findings underscore the need for additional research to confirm these preliminary results and investigate the long-term effects of COVID-19 vaccination on corneal transplants, aiming to provide evidence-based guidance to healthcare providers and patients.

New-onset of rheumatic diseases following COVID-19 vaccination: the report of three cases and a literature review.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Autoimmune rheumatic diseases and COVID-19 vaccination: a retrospective cross-sectional study from Astana.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has had an unprecedented impact on people around the world, particularly those who were suffering from autoimmune rheumatic diseases (AIRDs). The world community acknowledges the significance of COVID-19 vaccination in patients with autoimmune disorders and emphasizes the priority of this category to receive vaccination over the general population. Although many studies have been published since the first phases of vaccination all over the world, multiple related factors still need to be further investigated. Material and methods: We investigated the COVID-19 vaccination status in patients with AIRDs, by performing a cross-sectional, interview-based study filled in by patients attending their clinics in the Astana city, capital of Kazakhstan, from April to July 2023. The survey questionnaire consisted of a set of questions, concerning patient characteristics, treatment details, accepted vaccines and characteristics of COVID-19 infection. The study objectives were to evaluate vaccine hesitancy, adverse effects, breakthrough infections and flare of underlying rheumatic disease in this population subgroup. Results: There were 193 participants, with a median age of 50.3 ±12.9 years. Among them, 62 (32.1%) were vaccinated with at least single dose of vaccine, 16 (25.8%) of whom were fully vaccinated. The commonest (89; 68%) reason for vaccine hesitancy was a fear of autoimmune disease worsening. Vaccine-related adverse effects (AEs) were reported by 66.7% of patients. We found that vaccination provoked AIRD exacerbation in 19% of patients with AEs. Eight patients reported flare of pre-existing rheumatic disease after vaccination. The incidence of breakthrough infections was similar in the groups of vaccinated individuals (n = 12), 12.9% of whom were partially and 6.5% fully vaccinated. Conclusions: The vaccination was found to be safe in patients with rheumatic diseases. Fear of autoimmune status was the major reason for vaccine reluctance. All reported adverse events were minor. The minority subgroup within the sample had subsequent breakthrough infections or autoimmune disease flare-ups.

Causes and Effects of COVID-19 Vaccine Hesitancy Among Pregnant Women and its Association with Adverse Maternal, Placental, and Perinatal Outcomes.

Populations identified to be severely affected by COVID-19, such as pregnant patients, require special consideration in vaccine counseling, access, and provider education. Maternal infection with COVID-19 poses a significant risk to the maternal-fetal dyad with known adverse placenta destruction [1-5]. Despite the widespread access and availability of vaccinations, vaccine hesitancy continues to persist and is highly prevalent in pregnant populations [6-9]. Addressing the multitude of social ecological factors surrounding vaccine hesitancy can aid in providing holistic counseling [10]. However, such factors are foremost shaped by maternal concern over possible fetal effects from vaccination. While changes in policy can help foster vaccine access and acceptance, increasing global provider education and incorporation of motivational interviewing skills are the first steps towards increasing maternal acceptance.

Factors associated with intention to be vaccinated with the COVID-19 booster dose: a cross-sectional study in Peru.

Introduction: The pandemic of COVID-19 continues to impact people worldwide, with more than 755 million confirmed cases and more than 6.8 million reported deaths. Although two types of treatment, antiviral and immunomodulatory therapy, have been approved to date, vaccination has been the best method to control the spread of the disease. Objective: To explore factors associated with the intention to be vaccinated with the COVID-19 booster dose in Peru. Material and Methods: Cross-sectional study, using virtual and physical surveys of adults with two or more doses of COVID-19 vaccine, where the dependent variable was the intention to be vaccinated (IBV) with the booster dose. We calculated prevalence ratios with 95% confidence intervals, using generalized linear models of the Poisson family with robust varying, determining associations between sociodemographic, clinical, and booster dose perception variables. Results: Data from 924 adults were analyzed. The IBV of the booster doses was 88.1%. A higher prevalence was associated with being male (aPR = 1.05; 95% CI [1.01-1.10]), having a good perception of efficacy and protective effect (PR = 3.69; 95% CI [2.57-5.30]) and belonging to the health sector (PR = 1.10; 95% CI [1.04-1.16]). There was greater acceptance of the recommendation of physicians and other health professionals (aPR = 1.40; 95% CI [1.27-1.55]). Conclusions: Factors associated with higher IBV with booster dose include male gender, health sciences, physician recommendation, and good perception of efficacy.

Heritage and hesitancy: how preference for traditional Chinese medicine influences vaccine attitudes.

Introduction: Vaccine hesitancy, amplified by the COVID-19 pandemic, is a pressing public health challenge. This study investigates the association between Traditional Chinese Medicine (TCM) preference and COVID-19 vaccine hesitancy within China. Methods: The study uses data from the 2021 Chinese General Social Survey (CGSS) (N = 2,690). Logistic regressions and Karlson-Holm-Breen (KHB) method are employed to analyzed the relationship between TCM preference and vaccine hesitancy. Results: The study reaffirms prior findings by revealing a robust and stable association between TCM preference and vaccine hesitancy, which remains unaffected by socioeconomic and demographic confounders, as well as institutional trust dynamics of healthcare system. Contrary to expectations, TCM enthusiasts do not exhibit vaccine hesitancy based on divergent epistemological views concerning vaccine risks and immunity acquisition compared to biomedicine. Discussion: This research enriches understandings of the intricate relations between healthcare paradigms and vaccine attitudes, inviting further inquiry into the role of CAM in shaping vaccination behaviors across different cultures and contexts. The insights bear significant public health implications for enhancing vaccine acceptance and coverage, particularly among populations where CAM practices wield substantial influence.

The Status and Influencing Factors of COVID-19 Vaccination for 3-7-Year-Old Children Born Prematurely.

Objective: To explore the status and influencing factors of COVID-19 vaccination for 3-7-year-old children born prematurely. Methods: A questionnaire was administered to parents of preterm infants born between 1 January 2016 and 31 December 2019 in Gansu Maternal and Child Health Hospital using convenience sampling. Results: It was found that 96.81% of 282 parents had known about COVID-19 vaccines and acquired COVID-19- and vaccine-related knowledge primarily through WeChat (104/282, 36.88%) and TikTok (91/282, 32.27%). Most parents of the group whose children were vaccinated with a COVID-19 vaccine believed that this approach was effective in preventing COVID-19 (49.75%), whereas most parents of the group whose children were not vaccinated were worried about the adverse reaction and safety of the vaccine (45.88%). According to the regression analysis, the risk factors of children born prematurely receiving a COVID-19 vaccine were no vaccination against COVID-19 in the mothers (odds ratio [OR]=48.489, 95% CI: 6.524-360.406) and in younger children (OR=12.157, 95% CI: 6.388-23.139). Previous history of referral (OR=0.229, 95% CI: 0.057-0.920), history of diseases (OR=0.130, 95% CI: 0.034-0.503) and high educational level of guardians (OR=0.142, 95% CI: 0.112-0.557) were protective factors for children born prematurely to receive COVID-19 vaccination. Conclusion: There is a relatively high proportion of children born prematurely receiving COVID-19 vaccination, but some people still have concerns. Publicity in the later stage can be conducted through WeChat, TikTok and other social media platforms, with special attention paid to the populations with lower education levels.

TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: candidate selection in a preclinical murine model.

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform.

COVID-19 pediatric vaccine authorization, FDA authority, and individual misperception of risk.

Vaccines are one component to the public health strategies to alleviate the COVID-19 pandemic. Hesitancy regarding COVID-19 vaccines in the United States has been problematic, which is not surprising given increasing overall vaccine hesitancy in recent decades. Most vaccines are administered during childhood years. Consequently, understanding hesitancy toward administration of vaccines in this age group may provide insight into possible interventions to reduce vaccine hesitancy. The present study analyzed a subset of over 130,000 public comments posted in response to a notice of meeting of the vaccine advisory group to the Food and Drug Administration. The meeting addressed whether to recommend Emergency Use Authorization ('EUA') of the COVID-19 vaccine for children ages 5-11. The results of the study demonstrate that most comments opposed EUA and these comments were associated with statements that indicated misperceptions of risk. Findings provide interesting insights regarding the role of public comments generally but also suggest that the public participation process in notice and comment can be modified to serve as an intervention to align individual perceptions of risk more closely with evidence-based assessment of risk. In addition, the findings provide opportunities to consider strategies for public health messaging.

Facile generation of heterotelechelic poly(2-oxazoline)s towards accelerated exploration of poly(2-oxazoline)-based nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers pre-pared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of hetero-telechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain-end, allowing the selective introduction of N-, S-, O-nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para-fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well-defined lipid-polymer conjugates and POx-polypeptide block-copolymers, which are well-suited for drug and gene delivery. Furthermore, we investigated the application of a lipid-POx conjugate for the formulation and delivery of mRNA-loaded lipid nanoparticles for immunization against the SARS-COV-2 virus, underscoring the value of POx as a biocompatible polymer platform.

Enablers and barriers to vaccine uptake and handwashing practices to prevent and control COVID-19 in Kenya, Uganda, and Tanzania: a systematic review.

The global emergence of coronavirus disease 2019 (COVID-19) posed unprecedented challenges, jeopardizing decades of progress in healthcare systems, education, and poverty eradication. While proven interventions such as handwashing and mass vaccination offer effective means of curbing COVID-19 spread, their uptake remains low, potentially undermining future pandemic control efforts. This systematic review synthesized available evidence of the factors influencing vaccine uptake and handwashing practices in Kenya, Uganda, and Tanzania in the context of COVID-19 prevention and control. We conducted an extensive literature search across PubMed, Science Direct, and Google Scholar databases following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Out of 391 reviewed articles, 18 were eligible for inclusion. Some of the common barriers to handwashing in Kenya, Uganda, and Tanzania included lack of trust in the government's recommendations or messaging on the benefits of hand hygiene and lack of access to water, while some of the barriers to vaccine uptake included vaccine safety and efficacy concerns and inadequate awareness of vaccination sites and vaccine types. Enablers of handwashing practices encompassed hand hygiene programs and access to soap and water while those of COVID-19 vaccine uptake included improved access to vaccine knowledge and, socio-economic factors like a higher level of education. This review underscores the pivotal role of addressing these barriers while capitalizing on enablers to promote vaccination and handwashing practices. Stakeholders should employ awareness campaigns and community engagement, ensure vaccine and hygiene resources' accessibility, and leverage socio-economic incentives for effective COVID-19 prevention and control. Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD42023396303].

Immunogenicity and safety of concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine in Chinese adults: An open-label, randomized, controlled trial.

The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2-499.0) vs. 497.4 (95%CI: 377.5-655.3); H3N2: 66.9 (95%CI: 56.1-79.8) vs. 81.4 (95%CI: 67.9-97.5); Yamagata: 95.6 (95%CI: 79.0-115.8) vs. 74.3 (95%CI: 58.6-94.0); and Victoria: 48.5 (95%CI: 37.6-62.6) vs. 65.8 (95%CI: 49.0-88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.