In this paper,based on the SVIQR model we develop a stochastic epidemic model with multiple vaccinations and time delay.Firstly,we prove the existence and uniqueness of the global positive solution of the model,and co...In this paper,based on the SVIQR model we develop a stochastic epidemic model with multiple vaccinations and time delay.Firstly,we prove the existence and uniqueness of the global positive solution of the model,and construct suitable functions to obtain sufficient conditions for disease extinction.Secondly,in order to effectively control the spread of the disease,appropriate control strategies are formulated by using optimal control theory.Finally,the results are verified by numerical simulation.展开更多
AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this population.METHODS The electronic medical reco...AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this population.METHODS The electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed antitumor necrosis factor alpha(anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words "inflammatory bowel disease", "immunization", "vaccination", "pneumococcal", "varicella", and "hepatitis B". Non-human and non-English language studies were excluded. Search results were reviewed by authors toselect articles that addressed safety and efficacy of immunizations in inflammatory bowel disease.RESULTS A total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients(17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies. CONCLUSION Immunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy.展开更多
Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccinatio...Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant.Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.展开更多
The coronavirus disease 2019(COVID-19)pandemic has put standard,routine childhood vaccinations at risk worldwide.The disruption in vaccine coverage has resulted in a negative impact on the health of children,with some...The coronavirus disease 2019(COVID-19)pandemic has put standard,routine childhood vaccinations at risk worldwide.The disruption in vaccine coverage has resulted in a negative impact on the health of children,with some races,ethnicities,age groups,areas of settlement,and parts of the world affected more than others.This literature review studied and examined the impact of COVID-19 on infant,child,and adolescent vaccinations.Retrospectively,the analysis showed a decline,delays,or interruptions in the coverage of vaccines during the pandemic and a decline in some countries'pre-pandemic and post-pandemic eras.Necessary attempts and efforts should be made for these delayed and missed vaccinations,as failure to do so could put children's health at risk.Thus,priority should be directed at instituting catch-up programs to support vaccine uptake and decrease the probability of acquiring vaccine-preventable diseases.展开更多
AIM To study the uptake, barriers and motivators of influen-za, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries.METHODS A cross-sectional survey among the Gulf Coop...AIM To study the uptake, barriers and motivators of influen-za, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries.METHODS A cross-sectional survey among the Gulf Cooperation Council(GCC) countries' residents. Data collected electronically through a smartphone app. The survey variables aimed to investigate the respondents' awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections. Collected data concerning the respondents' socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine. The data were analysed statistically using the SPSS v.23.0. Differences in the characteristics of users from different countries were quantified through bivariate analysis. Other important variables and controlling factors were studied using logistic regression. RESULTS A total of 1812 respondents participated in the study. Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases. The overall uptake of influenza vaccine was 17%(21% among "at risk" people) and ranged from 15% in Saudi Arabia to 24% in Qatar. Doctor's advice(23%) and a perception of having low body immunity(21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine(43%) was the main barrier. The overall uptake of pneumococcal vaccine in the preceding three years was 22%(25% among "at risk" individuals) and ranged from 0% in Bahrain to 79% in Kuwait. The overall uptake of pertussis vaccine was 16%(31% among "vulnerable" people), and ranged from 7% in Saudi Arabia to 75% in Oman. The overall uptake of meningococcal vaccine was 20%(29% among the "at risk" people) and ranged from 3% in Oman to 50% in Bahrain.CONCLUSION The vaccination uptake across GCC countries is suboptimal and varies widely across the countries. Further research is needed to unearth the reasons and formulate action plan.展开更多
Introduction: Despite the enormous resources deployed and the success achieved in vaccination, reducing the number of children who remain unvaccinated remains a major operational challenge in certain countries. In 201...Introduction: Despite the enormous resources deployed and the success achieved in vaccination, reducing the number of children who remain unvaccinated remains a major operational challenge in certain countries. In 2014, the Kalemie Expanded Program of Immunization outpost in the Democratic Republic of the Congo was faced with a high number of unvaccinated children. They instituted a “token” catch-up system based on a collaborative approach with community health workers. This study aims to document the effects of this strategy on vaccination coverage. Methods: This study was a comparative quasi-experimental test/control study. The “test” health area was Undugu where the catch-up strategy was implemented and the “control” health area was Kanunka. A vaccination coverage survey was conducted according to the WHO method in both health areas, examining children aged 12 to 23 months. The proportions were compared using a Pearson chi-square test and the odds ratios were estimated. Results: Vaccine coverage was significantly higher in the “test” health area for all the antigens. Full vaccination coverage was 69.4% in the “test” health area versus 31% in the “control” health area, with a 4.7 times greater chance of being fully vaccinated in the “test” health area (OR: 4.7;CI 95% [3.1 - 7.2];p = 0.0001). Conclusion: This study demonstrates the value of a strategy that can increase access to vaccination and use of vaccination services, leading to a reduction in inequality in this area. However, this is linked to adapting the collaborative model on which it is based. This must be taken into consideration in plans to reproduce the findings.展开更多
The evolution of the HIV following migratory phenomenons is reported in an interesting study carried on for 15 years. Polymerase Chain Reaction (PCR) is a technique in molecular biology that amplifies a specific regio...The evolution of the HIV following migratory phenomenons is reported in an interesting study carried on for 15 years. Polymerase Chain Reaction (PCR) is a technique in molecular biology that amplifies a specific region of deoxyribonucleic acid (DNA), and has been useful in the molecular characterization of viruses as poxviruses. In many countries, such as?Italy,the vaccinations are included in the so-called sanitary obliged not coercive treatments. This means that the obligation is anticipated for all the subjects belonging to one determined range of age to undergo some vaccinations, but these are not subministrated by force in case of refusal. The legitimacy of the obligatory vaccination against the smallpox, with all the risks connected,?stated that such “risks were too much reduced to be seriously taken in consideration for the benefits produced on the collectivity”.?To ratify this obligation brings, however, to the reimbursement of the?incidental?damages produced by the vaccination. Nevertheless, mass vaccination against smallpox continues to be a leading initiative in western countries to guard against bioterrorist attack.展开更多
Objectives: To identify the obstacles and issues that hinder effective cancer prevention efforts in Ukraine. The study aims to provide a comprehensive assessment of the barriers to cancer prevention, including both in...Objectives: To identify the obstacles and issues that hinder effective cancer prevention efforts in Ukraine. The study aims to provide a comprehensive assessment of the barriers to cancer prevention, including both infrastructure and behavioral factors, and identify potential solutions to address these challenges. Study Design: Comprehensive literature review. Methods: The following databases were searched: National Center for Biotechnology Information (NCBI) and PubMed (U.S. National Library of Medicine at the National Institutes of Health). The keywords used in the search included “Cervical Cancer”, “Human Papillomavirus Vaccination (HPV)”, “Ukraine”, “Eastern Europe”, “Healthcare Infrastructure in Disasters”, “Cervical Cancer Prevention”, “Pap Smear”, and “HPV Testing”. Results: A total of 3500 articles were screened. A total of 65 articles met the inclusion criteria. Limited public awareness and limited access to vaccination and screening, combined with inadequate treatment facilities lead to higher rates of cervical cancer. The COVID pandemic, war with Russia, and the Chernobyl disaster are significant factors for the low level of vaccination in Ukraine. Conclusion: The prevention and treatment of cervical cancer in Ukraine face significant challenges due to the inadequate HPV vaccination rates and screening by cytology. Efforts to improve funding and increase education of both the population and health care providers are necessary to increase interventions such as HPV vaccination, cervical cytology, and HPV testing to reduce cervical cancer rates in Ukraine.展开更多
This study evaluates the distribution of COVID-19 cases and mass vaccination campaigns from January 2020 to April 2023. There are over 235,000 COVID-19 cases and over 733,000 vaccinations across the 159 counties in th...This study evaluates the distribution of COVID-19 cases and mass vaccination campaigns from January 2020 to April 2023. There are over 235,000 COVID-19 cases and over 733,000 vaccinations across the 159 counties in the state of Georgia. Data on COVID-19 was acquired from usafact.org while the vaccination records were obtained from COVID-19 vaccination tracker. The spatial patterns across the counties were analyzed using spatial statistical techniques which include both global and local spatial autocorrelation. The study further evaluates the effect of vaccination and selected socio-economic predictors on COVID-19 cases across the study area. The result of hotspot analysis reveals that the epicenters of COVID-19 are distributed across Cobb, Fulton, Gwinnett, and DeKalb counties. It was also affirmed that the vaccination records followed the same pattern as COVID-19 cases’ epicenters. The result of the spatial error model performed well and accounted for a considerable percentage of the regression with an adjusted R squared of 0.68, Akaike Information Criterion (AIC) 387.682 and Breusch-Pagan of 9.8091. ESDA was employed to select the main explanatory variables. The selected variables include vaccination, population density, percentage of people that do not have health insurance, black race, Hispanic and these variables accounted for 68% of the number of COVID-19 cases in the state of Georgia during the study period. The study concludes that both COVID-19 cases and vaccinated individuals have spatial peculiarities across counties in Georgia state. Lastly, socio-economic variables and vaccination are very important to reduce the vulnerability of individuals to COVID-19 disease.展开更多
Infections are a major cause of morbidity and mortality in the elderly. Improvements in health care prevention including vaccinations and treatment have led to an increase in the birth life expectancy. The vaccines th...Infections are a major cause of morbidity and mortality in the elderly. Improvements in health care prevention including vaccinations and treatment have led to an increase in the birth life expectancy. The vaccines that are now recommended for people over 60 are influenza, herpes zoster and a vaccine combining tetanus toxoid, reduced diphtheria toxoid, and pneumococcal vaccine. Our aim was to estimate the prevelance of vaccination among diabetic patients attending in Tepecik Training Hospital and in Ege University Faculty of Medicine. Patients and Methods: Individuals at or over the age of 60 who were attending to Tepecik Training Hospital and at Ege University Faculty of Medicine. Department of Internal Medicine was targeted from February to May 2014. Our data are collected from the patients face to face by questionnaire. Results: A total of 274 elderly patients with a mean ± SD (range) age of 72 ± 6 (62 - 93) years were questioned. The vaccination ratios were determined as 34% (93) for influenza, 9.5% (26) for pneumococcal, 10.6% (27) for tetanus vaccine. The patients were divided in two groups as diabetics and non-diabetics. The influenza vaccination rate is 38.1% in diabetic patients, rate of 31.8% in non-diabetic patients, the pneumococcal vaccine rate is 13.4% in diabetic patients, rate of 7.39% in non-diabetic patients. The tetanus vaccination rate is 9.28% in diabetic patients, rate of 11.36% in non-diabetic patients. No statistically significant difference between two groups was determined.展开更多
Routine pediatric vaccination is one of the most effective public health inter-ventions for the control of a number of fatal diseases.However,during the coronavirus disease 2019 pandemic,routine pediatric vaccination ...Routine pediatric vaccination is one of the most effective public health inter-ventions for the control of a number of fatal diseases.However,during the coronavirus disease 2019 pandemic,routine pediatric vaccination rates were severely affected by disruptions of health services and vaccine confidence issues.Governments and the United Nations have taken measures to re-establish routine pediatric vaccination,while additional efforts are needed to catch up and develop plans to ensure routine vaccination services for the future pandemics.展开更多
Background:Although the three vaccines against coronavirus disease 2019(Covid-19)that have received emergency use authorization in the United States are highly effective,breakthrough infections are occurring.Data are ...Background:Although the three vaccines against coronavirus disease 2019(Covid-19)that have received emergency use authorization in the United States are highly effective,breakthrough infections are occurring.Data are needed on the serial use of homologous boosters(same as the primary vaccine)and heterologous boosters(different from the primary vaccine)in fully vaccinated recipients.展开更多
The striking differences and similarities between the “Spanish-flu” of 1918 and the Coronavirus disease of 2019 (COVID-19) are analyzed. Progress in medicine and technology and in particular the availability of vacc...The striking differences and similarities between the “Spanish-flu” of 1918 and the Coronavirus disease of 2019 (COVID-19) are analyzed. Progress in medicine and technology and in particular the availability of vaccines has decreased the death probability from about 2% for the Spanish-flu, to about 10<sup>-4</sup> in the UK and 10<sup>-3</sup> in Italy, USA, Canada, San Marino and other countries for COVID-19. The logistic map reproduces most features of the disease and may be of guidance for predictions and future steps to be taken in order to contrast the virus. We estimate 6.4 × 10<sup>7</sup> deceases worldwide without the vaccines, this value decreases to 1.6 × 10<sup>7</sup> with the current vaccination rate. In November 2021, the number of deceased worldwide was 5.1 × 10<sup>6</sup>. To reduce the fatalities further, it is imperative to increase the vaccination rate worldwide to at least 120 millions/day and the AstraZeneca vaccine due to its efficacity and cost is a possible route to accomplish this.展开更多
Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic g...Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
Objective:To evaluate the cost-effectiveness of annual trivalent inactivated influenza vaccine(IIV3)under the context of Zhejiang province.Methods:A state transition simulation model was constructed to estimate the he...Objective:To evaluate the cost-effectiveness of annual trivalent inactivated influenza vaccine(IIV3)under the context of Zhejiang province.Methods:A state transition simulation model was constructed to estimate the health and economic outcomes of IIV3 vaccination program compared to no vaccination for hypothetical cohorts of Zhejiang province stratified by age and risk status.Model input parameters were chosen based on published literatures and expert advices.The analysis used societal perspectives and a one-year time horizon,and permanent outcomes were also included.The primary outcome was the incremental cost-effectiveness ratio(ICER),with expression of US dollars per quality adjusted life years(QALYs)gained.Results:In subgroups not at high risk for influenza-related complications(non-high risk subgroup),ICER ranged from $6268/QALY(for adults aged 50-64 years)to $11260/QALY(for children aged from 6 months to 4 years).In subgroups at high risk for influenza-related complications(high risk subgroup),ICER ranged from cost-saving(adults aged≥65 years)to $5260/QALY(for children aged from 6 months to 4 years).ICER were most sensitive to changes in probability of influenza illness,cost of hospitalization,and probability of death for adults aged 18-49 years with non-high risk status.Conclusions:ICERs of annual influenza vaccination varied by age and risk status but were less than the Gross Domestic Product(GDP)per capita of Zhejiang province($17745 in 2023),which remained cost-effective for all-age and different risk status groups from a societal perspective.展开更多
A universal cytomegalovirus （CMV） vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transm...A universal cytomegalovirus （CMV） vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transmission would reduce CMV congenital disease and CMV-associated still births and leave populations less susceptible to opportunistic CMV disease. Thus, a vaccination against this virus has long been recognized for the potential of enormous health-care savings because congenital damage is life-long and existing anti-viral options are limited. Vaccine researchers, industry leaders, and regulatory representatives have discussed the challenges posed by clinical efficacy trials that would lead to a universal CMV vaccine, reviewing the links between infection and disease, and identifying settings where disrupting viral transmission might provide a surrogate endpoint for disease prevention. Reducing the complexity of such trials would facilitate vaccine development. Children and adolescents are the targets for universal vaccination, with the expectation of protecting the offspring of immunized women. Given that a majority of females worldwide experience CMV infection during childhood, a universal vaccine must boost natural immunity and reduce transmission due to reactivation and re-infection as well as primary infection during pregnancy. Although current vaccine strategies recognize the value of humoral and cellular immunity, the precise mechanisms that act at the placental interface remain elusive. Immunity resulting from natural infection appears to limit rather than prevent reactivation of latent viruses and susceptibility to re-infection, leaving a challenge for universal vaccination to improve upon natural immunity levels. Despite these hurdles, early phase clinical trials have achieved primary end points in CMV seronegative subjects. Efficacy studies must be expanded to mixed populations of CMV-naive and naturally infected subjects to understand the overall efficacy and potential. Together with CMV vaccine candidates currently in clinical development, additional promising preclinical strategies continue to come forward; however, these face limitations due to the insufficient understanding of host defense mechanisms that prevent transmission, as well as the age-old challenges of reaching the appropriate threshold of immunogenicity, efficacy, durability and potency. This review focuses on the current understanding of natural and CMV vaccine-induced protective immunity.展开更多
In the European Union,mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response.Now,vaccination campaigns are focusing on booster doses,and primary vaccination...In the European Union,mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response.Now,vaccination campaigns are focusing on booster doses,and primary vaccinations have all but halted.Still,52 million European adults are unvaccinated.We investigated if reaching the still unvaccinated population in future vaccination campaigns would substantially decrease the current burden of COVID-19,which is substantial.We focused on vaccination homophily,whereby those who are unvaccinated are mostly in contact with other unvaccinated,making COVID-19 circulation easier.We quantified vaccination homophily and estimated its impact on COVID-19 circulation.We used an online survey of 1,055,286 people from 22 European countries during early 2022.We computed vaccination homophily as the association between reported vaccination status and perceived vaccination uptake among one's own social contacts,using a case-referent design and a hierarchical logistic model.We used this information in an analysis of the COVID-19 reproduction ratio to determine the impact of vaccine homophily in transmission.Vaccination homophily was present and strong everywhere:the average odds ratio of being vaccinated for a 10-percentage-point increase in coverage among contacts was 1.66(95%CI=(1.60,1.72)).Homophily was positively associated with the strictness of COVID-19-related restrictions in 2020(Pearson=0.49,P=.03).In the countries studied,12%-to-18%of the reproduction ratio would be attributable to vaccine homophily.Reducing vaccination homophily may curb the reproduction ratio substantially even to the point of preventing recurrent epidemic waves.In addition to boosting those already vaccinated,increasing primary vaccination should remain a high priority in future vaccination campaigns,to reduce vaccination homophily:this combined strategy may decrease COVID-19 burden.展开更多
From the beginning of the COVID-19 pandemic,universities have experienced unique challenges due to their dual nature as a place of education and residence.Current research has explored non-pharmaceutical approaches to...From the beginning of the COVID-19 pandemic,universities have experienced unique challenges due to their dual nature as a place of education and residence.Current research has explored non-pharmaceutical approaches to combating COVID-19,including representing in models different categories such as age groups.One key area not currently well represented in models is the effect of pharmaceutical preventative measures,specifically vaccinations,on COVID-19 spread on college campuses.There remain key questions on the sensitivity of COVID-19 infection rates on college campuses to potentially time-varying vaccine immunity.Here we introduce a compartment model that decomposes a campus population into constituent subpopulations and implements vaccinations with timevarying efficacy.We use this model to represent a campus population with both vaccinated and unvaccinated individuals,and we analyze this model using two metrics of interest:maximum isolation population and symptomatic infection.We demonstrate a decrease in symptomatic infections occurs for vaccinated individuals when the frequency of testing for unvaccinated individuals is increased.We find that the number of symptomatic infections is insensitive to the frequency of testing of the unvaccinated subpopulation once about 80%or more of the population is vaccinated.Through a Sobol’global sensitivity analysis,we characterize the sensitivity of modeled infection rates to these uncertain parameters.We find that in order to manage symptomatic infections and the maximum isolation population campuses must minimize contact between infected and uninfected individuals,promote high vaccine protection at the beginning of the semester,and minimize the number of individuals developing symptoms.展开更多
The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thr...The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately understood.Both infection and vaccination utilize the spike protein receptor-binding domain(RBD)of SARS-CoV-2.We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice.Further investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa variants.The RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−mice.Furthermore,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 cells.Our data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT.Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(No.3122025090)。
文摘In this paper,based on the SVIQR model we develop a stochastic epidemic model with multiple vaccinations and time delay.Firstly,we prove the existence and uniqueness of the global positive solution of the model,and construct suitable functions to obtain sufficient conditions for disease extinction.Secondly,in order to effectively control the spread of the disease,appropriate control strategies are formulated by using optimal control theory.Finally,the results are verified by numerical simulation.
文摘AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this population.METHODS The electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed antitumor necrosis factor alpha(anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words "inflammatory bowel disease", "immunization", "vaccination", "pneumococcal", "varicella", and "hepatitis B". Non-human and non-English language studies were excluded. Search results were reviewed by authors toselect articles that addressed safety and efficacy of immunizations in inflammatory bowel disease.RESULTS A total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients(17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies. CONCLUSION Immunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy.
文摘Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant.Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.
文摘The coronavirus disease 2019(COVID-19)pandemic has put standard,routine childhood vaccinations at risk worldwide.The disruption in vaccine coverage has resulted in a negative impact on the health of children,with some races,ethnicities,age groups,areas of settlement,and parts of the world affected more than others.This literature review studied and examined the impact of COVID-19 on infant,child,and adolescent vaccinations.Retrospectively,the analysis showed a decline,delays,or interruptions in the coverage of vaccines during the pandemic and a decline in some countries'pre-pandemic and post-pandemic eras.Necessary attempts and efforts should be made for these delayed and missed vaccinations,as failure to do so could put children's health at risk.Thus,priority should be directed at instituting catch-up programs to support vaccine uptake and decrease the probability of acquiring vaccine-preventable diseases.
基金Supported by Medication Safety Research Chair,Deanship of Research Chairs,King Saud University
文摘AIM To study the uptake, barriers and motivators of influen-za, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries.METHODS A cross-sectional survey among the Gulf Cooperation Council(GCC) countries' residents. Data collected electronically through a smartphone app. The survey variables aimed to investigate the respondents' awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections. Collected data concerning the respondents' socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine. The data were analysed statistically using the SPSS v.23.0. Differences in the characteristics of users from different countries were quantified through bivariate analysis. Other important variables and controlling factors were studied using logistic regression. RESULTS A total of 1812 respondents participated in the study. Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases. The overall uptake of influenza vaccine was 17%(21% among "at risk" people) and ranged from 15% in Saudi Arabia to 24% in Qatar. Doctor's advice(23%) and a perception of having low body immunity(21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine(43%) was the main barrier. The overall uptake of pneumococcal vaccine in the preceding three years was 22%(25% among "at risk" individuals) and ranged from 0% in Bahrain to 79% in Kuwait. The overall uptake of pertussis vaccine was 16%(31% among "vulnerable" people), and ranged from 7% in Saudi Arabia to 75% in Oman. The overall uptake of meningococcal vaccine was 20%(29% among the "at risk" people) and ranged from 3% in Oman to 50% in Bahrain.CONCLUSION The vaccination uptake across GCC countries is suboptimal and varies widely across the countries. Further research is needed to unearth the reasons and formulate action plan.
文摘Introduction: Despite the enormous resources deployed and the success achieved in vaccination, reducing the number of children who remain unvaccinated remains a major operational challenge in certain countries. In 2014, the Kalemie Expanded Program of Immunization outpost in the Democratic Republic of the Congo was faced with a high number of unvaccinated children. They instituted a “token” catch-up system based on a collaborative approach with community health workers. This study aims to document the effects of this strategy on vaccination coverage. Methods: This study was a comparative quasi-experimental test/control study. The “test” health area was Undugu where the catch-up strategy was implemented and the “control” health area was Kanunka. A vaccination coverage survey was conducted according to the WHO method in both health areas, examining children aged 12 to 23 months. The proportions were compared using a Pearson chi-square test and the odds ratios were estimated. Results: Vaccine coverage was significantly higher in the “test” health area for all the antigens. Full vaccination coverage was 69.4% in the “test” health area versus 31% in the “control” health area, with a 4.7 times greater chance of being fully vaccinated in the “test” health area (OR: 4.7;CI 95% [3.1 - 7.2];p = 0.0001). Conclusion: This study demonstrates the value of a strategy that can increase access to vaccination and use of vaccination services, leading to a reduction in inequality in this area. However, this is linked to adapting the collaborative model on which it is based. This must be taken into consideration in plans to reproduce the findings.
文摘The evolution of the HIV following migratory phenomenons is reported in an interesting study carried on for 15 years. Polymerase Chain Reaction (PCR) is a technique in molecular biology that amplifies a specific region of deoxyribonucleic acid (DNA), and has been useful in the molecular characterization of viruses as poxviruses. In many countries, such as?Italy,the vaccinations are included in the so-called sanitary obliged not coercive treatments. This means that the obligation is anticipated for all the subjects belonging to one determined range of age to undergo some vaccinations, but these are not subministrated by force in case of refusal. The legitimacy of the obligatory vaccination against the smallpox, with all the risks connected,?stated that such “risks were too much reduced to be seriously taken in consideration for the benefits produced on the collectivity”.?To ratify this obligation brings, however, to the reimbursement of the?incidental?damages produced by the vaccination. Nevertheless, mass vaccination against smallpox continues to be a leading initiative in western countries to guard against bioterrorist attack.
文摘Objectives: To identify the obstacles and issues that hinder effective cancer prevention efforts in Ukraine. The study aims to provide a comprehensive assessment of the barriers to cancer prevention, including both infrastructure and behavioral factors, and identify potential solutions to address these challenges. Study Design: Comprehensive literature review. Methods: The following databases were searched: National Center for Biotechnology Information (NCBI) and PubMed (U.S. National Library of Medicine at the National Institutes of Health). The keywords used in the search included “Cervical Cancer”, “Human Papillomavirus Vaccination (HPV)”, “Ukraine”, “Eastern Europe”, “Healthcare Infrastructure in Disasters”, “Cervical Cancer Prevention”, “Pap Smear”, and “HPV Testing”. Results: A total of 3500 articles were screened. A total of 65 articles met the inclusion criteria. Limited public awareness and limited access to vaccination and screening, combined with inadequate treatment facilities lead to higher rates of cervical cancer. The COVID pandemic, war with Russia, and the Chernobyl disaster are significant factors for the low level of vaccination in Ukraine. Conclusion: The prevention and treatment of cervical cancer in Ukraine face significant challenges due to the inadequate HPV vaccination rates and screening by cytology. Efforts to improve funding and increase education of both the population and health care providers are necessary to increase interventions such as HPV vaccination, cervical cytology, and HPV testing to reduce cervical cancer rates in Ukraine.
文摘This study evaluates the distribution of COVID-19 cases and mass vaccination campaigns from January 2020 to April 2023. There are over 235,000 COVID-19 cases and over 733,000 vaccinations across the 159 counties in the state of Georgia. Data on COVID-19 was acquired from usafact.org while the vaccination records were obtained from COVID-19 vaccination tracker. The spatial patterns across the counties were analyzed using spatial statistical techniques which include both global and local spatial autocorrelation. The study further evaluates the effect of vaccination and selected socio-economic predictors on COVID-19 cases across the study area. The result of hotspot analysis reveals that the epicenters of COVID-19 are distributed across Cobb, Fulton, Gwinnett, and DeKalb counties. It was also affirmed that the vaccination records followed the same pattern as COVID-19 cases’ epicenters. The result of the spatial error model performed well and accounted for a considerable percentage of the regression with an adjusted R squared of 0.68, Akaike Information Criterion (AIC) 387.682 and Breusch-Pagan of 9.8091. ESDA was employed to select the main explanatory variables. The selected variables include vaccination, population density, percentage of people that do not have health insurance, black race, Hispanic and these variables accounted for 68% of the number of COVID-19 cases in the state of Georgia during the study period. The study concludes that both COVID-19 cases and vaccinated individuals have spatial peculiarities across counties in Georgia state. Lastly, socio-economic variables and vaccination are very important to reduce the vulnerability of individuals to COVID-19 disease.
文摘Infections are a major cause of morbidity and mortality in the elderly. Improvements in health care prevention including vaccinations and treatment have led to an increase in the birth life expectancy. The vaccines that are now recommended for people over 60 are influenza, herpes zoster and a vaccine combining tetanus toxoid, reduced diphtheria toxoid, and pneumococcal vaccine. Our aim was to estimate the prevelance of vaccination among diabetic patients attending in Tepecik Training Hospital and in Ege University Faculty of Medicine. Patients and Methods: Individuals at or over the age of 60 who were attending to Tepecik Training Hospital and at Ege University Faculty of Medicine. Department of Internal Medicine was targeted from February to May 2014. Our data are collected from the patients face to face by questionnaire. Results: A total of 274 elderly patients with a mean ± SD (range) age of 72 ± 6 (62 - 93) years were questioned. The vaccination ratios were determined as 34% (93) for influenza, 9.5% (26) for pneumococcal, 10.6% (27) for tetanus vaccine. The patients were divided in two groups as diabetics and non-diabetics. The influenza vaccination rate is 38.1% in diabetic patients, rate of 31.8% in non-diabetic patients, the pneumococcal vaccine rate is 13.4% in diabetic patients, rate of 7.39% in non-diabetic patients. The tetanus vaccination rate is 9.28% in diabetic patients, rate of 11.36% in non-diabetic patients. No statistically significant difference between two groups was determined.
基金Supported by Scientific Research Foundation of Shanghai Municipal Health Commission of Changning District,No.20234Y038.
文摘Routine pediatric vaccination is one of the most effective public health inter-ventions for the control of a number of fatal diseases.However,during the coronavirus disease 2019 pandemic,routine pediatric vaccination rates were severely affected by disruptions of health services and vaccine confidence issues.Governments and the United Nations have taken measures to re-establish routine pediatric vaccination,while additional efforts are needed to catch up and develop plans to ensure routine vaccination services for the future pandemics.
文摘Background:Although the three vaccines against coronavirus disease 2019(Covid-19)that have received emergency use authorization in the United States are highly effective,breakthrough infections are occurring.Data are needed on the serial use of homologous boosters(same as the primary vaccine)and heterologous boosters(different from the primary vaccine)in fully vaccinated recipients.
文摘The striking differences and similarities between the “Spanish-flu” of 1918 and the Coronavirus disease of 2019 (COVID-19) are analyzed. Progress in medicine and technology and in particular the availability of vaccines has decreased the death probability from about 2% for the Spanish-flu, to about 10<sup>-4</sup> in the UK and 10<sup>-3</sup> in Italy, USA, Canada, San Marino and other countries for COVID-19. The logistic map reproduces most features of the disease and may be of guidance for predictions and future steps to be taken in order to contrast the virus. We estimate 6.4 × 10<sup>7</sup> deceases worldwide without the vaccines, this value decreases to 1.6 × 10<sup>7</sup> with the current vaccination rate. In November 2021, the number of deceased worldwide was 5.1 × 10<sup>6</sup>. To reduce the fatalities further, it is imperative to increase the vaccination rate worldwide to at least 120 millions/day and the AstraZeneca vaccine due to its efficacity and cost is a possible route to accomplish this.
文摘Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金funded by Medical and Health Science and Technology Project of Zhejiang province(Grant number:2023KY633).
文摘Objective:To evaluate the cost-effectiveness of annual trivalent inactivated influenza vaccine(IIV3)under the context of Zhejiang province.Methods:A state transition simulation model was constructed to estimate the health and economic outcomes of IIV3 vaccination program compared to no vaccination for hypothetical cohorts of Zhejiang province stratified by age and risk status.Model input parameters were chosen based on published literatures and expert advices.The analysis used societal perspectives and a one-year time horizon,and permanent outcomes were also included.The primary outcome was the incremental cost-effectiveness ratio(ICER),with expression of US dollars per quality adjusted life years(QALYs)gained.Results:In subgroups not at high risk for influenza-related complications(non-high risk subgroup),ICER ranged from $6268/QALY(for adults aged 50-64 years)to $11260/QALY(for children aged from 6 months to 4 years).In subgroups at high risk for influenza-related complications(high risk subgroup),ICER ranged from cost-saving(adults aged≥65 years)to $5260/QALY(for children aged from 6 months to 4 years).ICER were most sensitive to changes in probability of influenza illness,cost of hospitalization,and probability of death for adults aged 18-49 years with non-high risk status.Conclusions:ICERs of annual influenza vaccination varied by age and risk status but were less than the Gross Domestic Product(GDP)per capita of Zhejiang province($17745 in 2023),which remained cost-effective for all-age and different risk status groups from a societal perspective.
文摘A universal cytomegalovirus （CMV） vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transmission would reduce CMV congenital disease and CMV-associated still births and leave populations less susceptible to opportunistic CMV disease. Thus, a vaccination against this virus has long been recognized for the potential of enormous health-care savings because congenital damage is life-long and existing anti-viral options are limited. Vaccine researchers, industry leaders, and regulatory representatives have discussed the challenges posed by clinical efficacy trials that would lead to a universal CMV vaccine, reviewing the links between infection and disease, and identifying settings where disrupting viral transmission might provide a surrogate endpoint for disease prevention. Reducing the complexity of such trials would facilitate vaccine development. Children and adolescents are the targets for universal vaccination, with the expectation of protecting the offspring of immunized women. Given that a majority of females worldwide experience CMV infection during childhood, a universal vaccine must boost natural immunity and reduce transmission due to reactivation and re-infection as well as primary infection during pregnancy. Although current vaccine strategies recognize the value of humoral and cellular immunity, the precise mechanisms that act at the placental interface remain elusive. Immunity resulting from natural infection appears to limit rather than prevent reactivation of latent viruses and susceptibility to re-infection, leaving a challenge for universal vaccination to improve upon natural immunity levels. Despite these hurdles, early phase clinical trials have achieved primary end points in CMV seronegative subjects. Efficacy studies must be expanded to mixed populations of CMV-naive and naturally infected subjects to understand the overall efficacy and potential. Together with CMV vaccine candidates currently in clinical development, additional promising preclinical strategies continue to come forward; however, these face limitations due to the insufficient understanding of host defense mechanisms that prevent transmission, as well as the age-old challenges of reaching the appropriate threshold of immunogenicity, efficacy, durability and potency. This review focuses on the current understanding of natural and CMV vaccine-induced protective immunity.
基金based on survey results from University of Maryland.Partial support from EU grant MOOD(H2020-874850)ANR and Fondation de France-NoCOV(00105995)ANRS EMERGEN(ANRS0151)and Sorbonne Universite ISCD.
文摘In the European Union,mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response.Now,vaccination campaigns are focusing on booster doses,and primary vaccinations have all but halted.Still,52 million European adults are unvaccinated.We investigated if reaching the still unvaccinated population in future vaccination campaigns would substantially decrease the current burden of COVID-19,which is substantial.We focused on vaccination homophily,whereby those who are unvaccinated are mostly in contact with other unvaccinated,making COVID-19 circulation easier.We quantified vaccination homophily and estimated its impact on COVID-19 circulation.We used an online survey of 1,055,286 people from 22 European countries during early 2022.We computed vaccination homophily as the association between reported vaccination status and perceived vaccination uptake among one's own social contacts,using a case-referent design and a hierarchical logistic model.We used this information in an analysis of the COVID-19 reproduction ratio to determine the impact of vaccine homophily in transmission.Vaccination homophily was present and strong everywhere:the average odds ratio of being vaccinated for a 10-percentage-point increase in coverage among contacts was 1.66(95%CI=(1.60,1.72)).Homophily was positively associated with the strictness of COVID-19-related restrictions in 2020(Pearson=0.49,P=.03).In the countries studied,12%-to-18%of the reproduction ratio would be attributable to vaccine homophily.Reducing vaccination homophily may curb the reproduction ratio substantially even to the point of preventing recurrent epidemic waves.In addition to boosting those already vaccinated,increasing primary vaccination should remain a high priority in future vaccination campaigns,to reduce vaccination homophily:this combined strategy may decrease COVID-19 burden.
文摘From the beginning of the COVID-19 pandemic,universities have experienced unique challenges due to their dual nature as a place of education and residence.Current research has explored non-pharmaceutical approaches to combating COVID-19,including representing in models different categories such as age groups.One key area not currently well represented in models is the effect of pharmaceutical preventative measures,specifically vaccinations,on COVID-19 spread on college campuses.There remain key questions on the sensitivity of COVID-19 infection rates on college campuses to potentially time-varying vaccine immunity.Here we introduce a compartment model that decomposes a campus population into constituent subpopulations and implements vaccinations with timevarying efficacy.We use this model to represent a campus population with both vaccinated and unvaccinated individuals,and we analyze this model using two metrics of interest:maximum isolation population and symptomatic infection.We demonstrate a decrease in symptomatic infections occurs for vaccinated individuals when the frequency of testing for unvaccinated individuals is increased.We find that the number of symptomatic infections is insensitive to the frequency of testing of the unvaccinated subpopulation once about 80%or more of the population is vaccinated.Through a Sobol’global sensitivity analysis,we characterize the sensitivity of modeled infection rates to these uncertain parameters.We find that in order to manage symptomatic infections and the maximum isolation population campuses must minimize contact between infected and uninfected individuals,promote high vaccine protection at the beginning of the semester,and minimize the number of individuals developing symptoms.
基金the Canadian Institutes of Health Research(CIHR)Foundation grant(389035)CCOA Therapeutics Inc.research fund to Dr.H.N.CIHR grant for COVID-19(OV3-170344,SBC-171482,and VS1-175560)to Dr.H.Z.D.T.M.,Z.C.,and DK are recipients of the Queen Elizabeth II(QE-II)Graduate Scholarship,Ontario,Canada.S.S.is a recipient of the Canadian Blood Services postdoctoral award.D.T.M.is a recipient of a Graduate Scholarship,Department of Physiology,University of Toronto.Z.C.is the recipient of the Canadian Blood Services Graduate Scholarship,Ontario,Canada.C.S.is a recipient of a postdoctoral Mitacs award,University of Toronto.Z.L.is a recipient of Mitacs Accelerate Postdoctoral Fellowship.LL is a recipient of a scholarship from the University of Chinese Academy of Sciences.X.W.is a recipient of Killam Research Fellowship from the Canadian Council for the Arts.D.K.is also the recipient of the St.Michael’s Hospital Research Training Centre Scholarship and the 2021-2022 Vanier Canada Graduate Scholarships(Vanier CGS),and V.P.is the recipient of the CGS awarded by the CIHR.
文摘The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden.Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately understood.Both infection and vaccination utilize the spike protein receptor-binding domain(RBD)of SARS-CoV-2.We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice.Further investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa variants.The RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−mice.Furthermore,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 cells.Our data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT.Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.
