Modelling immunization strategies with cytomegalovirus vaccine candidates

2011 ◽  
Vol 139 (12) ◽  
pp. 1818-1826 ◽  
Author(s):  
R. S. AZEVEDO ◽  
M. AMAKU
Keyword(s):  
Congenital Infection ◽  
Vaccination Strategy ◽  
Phase Ii Clinical Trials ◽  
Immunization Strategies ◽  
Current Vaccine ◽  
Single Vaccination ◽  
Mixing Patterns ◽  
Duration Of Protection ◽  
The Impact ◽  
Induced Immunity

SUMMARYIn order to analyse the impact of vaccination against cytomegalovirus (CMV) on congenital infection incidence using current vaccines tested in phase II clinical trials, we simulated different scenarios by mathematical modelling, departing from the current vaccine characteristics, varying age at vaccination, immunity waning, vaccine efficacy and mixing patterns. Our results indicated that the optimal age for a single vaccination interval is from 2 to 6 months if there is no immunity waning. Congenital infection may increase if vaccine-induced immunity wanes before 20 years. Congenital disease should increase further when the mixing pattern includes transmission among children with a short duration of protection vaccine. Thus, the best vaccination strategy is a combined schedule: before age 1 year plus a second dose at 10–11 years. For CMV vaccines with low efficacy, such as the current ones, universal vaccination against CMV should be considered for infants and teenagers.

scholarly journals Understanding the Role of Duration of Vaccine Protection with MenAfriVac: Simulating Alternative Vaccination Strategies

2021 ◽  
Vol 9 (2) ◽  
pp. 461
Author(s):  
Andromachi Karachaliou Prasinou ◽  
Andrew J. K. Conlan ◽  
Caroline L. Trotter
Keyword(s):  
Booster Dose ◽  
Disease Incidence ◽  
Age Distribution ◽  
Vaccination Strategy ◽  
Older Children ◽  
Vaccine Protection ◽  
School Aged Children ◽  
Immunization Strategies ◽  
Duration Of Protection

We previously developed a transmission dynamic model of Neisseria meningitidis serogroup A (NmA) with the aim of forecasting the relative benefits of different immunisation strategies with MenAfriVac. Our findings suggested that the most effective strategy in maintaining disease control was the introduction of MenAfriVac into the Expanded Programme on Immunisation (EPI). This strategy is currently being followed by the countries of the meningitis belt. Since then, the persistence of vaccine-induced antibodies has been further studied and new data suggest that immune response is influenced by the age at vaccination. Here, we aim to investigate the influence of both the duration and age-specificity of vaccine-induced protection on our model predictions and explore how the optimal vaccination strategy may change in the long-term. We adapted our previous model and considered plausible alternative immunization strategies, including the addition of a booster dose to the current schedule, as well as the routine vaccination of school-aged children for a range of different assumptions regarding the duration of protection. To allow for a comparison between the different strategies, we use several metrics, including the median age of infection, the number of people needed to vaccinate (NNV) to prevent one case, the age distribution of cases for each strategy, as well as the time it takes for the number of cases to start increasing after the honeymoon period (resurgence). None of the strategies explored in this work is superior in all respects. This is especially true when vaccine-induced protection is the same regardless of the age at vaccination. Uncertainty in the duration of protection is important. For duration of protection lasting for an average of 18 years or longer, the model predicts elimination of NmA cases. Assuming that vaccine protection is more durable for individuals vaccinated after the age of 5 years, routine immunization of older children would be more efficient in reducing disease incidence and would also result in a fewer number of doses necessary to prevent one case. Assuming that elimination does not occur, adding a booster dose is likely to prevent most cases but the caveat will be a more costly intervention. These results can be used to understand important sources of uncertainty around MenAfriVac and support decisions by policymakers.

scholarly journals Immunization Strategies for Funding Multiple Inflation-Linked Retirement Income Benefits

Risks ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 60
Author(s):  
Cláudia Simões ◽  
Luís Oliveira ◽  
Jorge M. Bravo
Keyword(s):  
Interest Rate ◽  
Yield Curve ◽  
Risk Measure ◽  
Management Strategies ◽  
Interest Rate Risk ◽  
Insurance Companies ◽  
Retirement Income ◽  
Investment Strategies ◽  
Immunization Strategies ◽  
The Impact

Protecting against unexpected yield curve, inflation, and longevity shifts are some of the most critical issues institutional and private investors must solve when managing post-retirement income benefits. This paper empirically investigates the performance of alternative immunization strategies for funding targeted multiple liabilities that are fixed in timing but random in size (inflation-linked), i.e., that change stochastically according to consumer price or wage level indexes. The immunization procedure is based on a targeted minimax strategy considering the M-Absolute as the interest rate risk measure. We investigate to what extent the inflation-hedging properties of ILBs in asset liability management strategies targeted to immunize multiple liabilities of random size are superior to that of nominal bonds. We use two alternative datasets comprising daily closing prices for U.S. Treasuries and U.S. inflation-linked bonds from 2000 to 2018. The immunization performance is tested over 3-year and 5-year investment horizons, uses real and not simulated bond data and takes into consideration the impact of transaction costs in the performance of immunization strategies and in the selection of optimal investment strategies. The results show that the multiple liability immunization strategy using inflation-linked bonds outperforms the equivalent strategy using nominal bonds and is robust even in a nearly zero interest rate scenario. These results have important implications in the design and structuring of ALM liability-driven investment strategies, particularly for retirement income providers such as pension schemes or life insurance companies.

scholarly journals Anti-meningococcal B vaccination in Italian adolescents: a cost-effective health opportunity

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
D Panatto ◽  
P Landa ◽  
D Amicizia ◽  
P L Lai ◽  
E Lecini ◽  
...  
Keyword(s):  
Large Scale ◽  
Public Health Problem ◽  
Vaccination Strategy ◽  
Cost Effective ◽  
Dose Schedule ◽  
Developed Countries ◽  
Invasive Disease ◽  
International Setting ◽  
The Impact

Abstract Background Invasive disease due to Neisseria meningitidis (Nm) is a serious public health problem even in developed countries, owing to its high lethality rate (8-15%) and the invalidating sequelae suffered by many (up to 60%) survivors. As the microorganism is transmitted via the airborne route, the only available weapon in the fight against Nm invasive disease is vaccination. Our aim was to carry out an HTA to evaluate the costs and benefits of anti-meningococcal B (MenB) vaccination with Trumenba® in adolescents in Italy, while also considering the impact of this new vaccination strategy on organizational and ethics aspects. Methods A lifetime Markov model was developed. MenB vaccination with the two-dose schedule of Trumenba® in adolescents was compared with 'non-vaccination'. Two perspectives were considered: the National Health Service (NHS) and society. Three disease phases were defined: acute, post-acute and long-term. Epidemiological, economic and health utilities data were taken from Italian and international literature. The analysis was conducted by means of Microsoft Excel 2010®. Results Our study indicated that vaccinating adolescents (11th year of life) with Trumenba® was cost-effective with an ICER = € 7,912/QALY from the NHS perspective and € 7,758/QALY from the perspective of society. Vaccinating adolescents reduces the number of cases of disease due to meningococcus B in one of the periods of highest incidence of the disease, resulting in significant economic and health savings. Conclusions This is the first study to evaluate the overall impact of free MenB vaccination in adolescents both in Italy and in the international setting. Although cases of invasive disease due to meningococcus B are few, if the overall impact of the disease is adequately considered, it becomes clear that including anti-meningococcal B vaccination into the immunization program for adolescents is strongly recommended from the health and economic standpoints. Key messages Free, large-scale MenB vaccination is key to strengthening the global fight against invasive meningococcal disease. Anti-meningococcal B vaccination in adolescents is a cost-effective health opportunity.

scholarly journals Impact of national influenza vaccination strategy in severe influenza outcomes among the high-risk Portuguese population

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ausenda Machado ◽  
Irina Kislaya ◽  
Amparo Larrauri ◽  
Carlos Matias Dias ◽  
Baltazar Nunes
Keyword(s):  
High Risk ◽  
Influenza Vaccination ◽  
Seasonal Influenza ◽  
Vaccine Coverage ◽  
Vaccination Strategy ◽  
High Risk Population ◽  
Risk Population ◽  
Seasonal Influenza Vaccination ◽  
Severe Influenza ◽  
The Impact

Abstract Background All aged individuals with a chronic condition and those with 65 and more years are at increased risk of severe influenza post-infection complications. There is limited research on cases averted by the yearly vaccination programs in high-risk individuals. The objective was to estimate the impact of trivalent seasonal influenza vaccination on averted hospitalizations and death among the high-risk population in Portugal. Methods The impact of trivalent seasonal influenza vaccination was estimated using vaccine coverage, vaccine effectiveness and the number of influenza-related hospitalizations and deaths. The number of averted events (NAE), prevented fraction (PF) and number needed to vaccinate (NVN) were estimated for seasons 2014/15 to 2016/17. Results The vaccination strategy averted on average approximately 1833 hospitalizations and 383 deaths per season. Highest NAE was observed in the ≥65 years population (85% of hospitalizations and 95% deaths) and in the 2016/17 season (1957 hospitalizations and 439 deaths). On average, seasonal vaccination prevented 21% of hospitalizations in the population aged 65 and more, and 18.5% in the population with chronic conditions. The vaccination also prevented 29% and 19.5% of deaths in each group of the high-risk population. It would be needed to vaccinate 3360 high-risk individuals, to prevent one hospitalization and 60,471 high-risk individuals to prevent one death. Conclusion The yearly influenza vaccination campaigns had a sustained positive benefit for the high-risk population, reducing hospitalizations and deaths. These results can support public health plans toward increased vaccine coverage in high-risk groups.

scholarly journals Rubella Antibody Levels in School-Aged Children in Newfoundland: Implications for a Two-Dose Rubella Vaccination Strategy

1997 ◽  
Vol 8 (2) ◽  
pp. 85-88 ◽  
Author(s):  
Samuel Ratnam ◽  
Roy West ◽  
Veeresh Gadag ◽  
Brett Williams ◽  
Elizabeth Oates
Keyword(s):  
Single Dose ◽  
Screening Program ◽  
Serum Antibody ◽  
Vaccination Strategy ◽  
Reproductive Age ◽  
Cluster Sampling ◽  
Age Group ◽  
School Aged Children ◽  
Rubella Vaccination ◽  
The Impact

OBJECTIVE: To determine the prevailing levels of rubella immunity among school-aged children who received a single dose of measles-mumps-rubella (MMR) vaccine at one year of age.DESIGN: Cross-sectional study with a two stage cluster sampling of randomly picked schools across the province of Newfoundland.STUDY POPULATION AND METHODS: A total of 1053, five to 17-year-old children were enrolled; vaccination history was verified through official records; and a sample of blood was taken. Rubella immunity was determined by enzyme immunoassay based on a serum antibody protective cut-off titre of more than 10 IU.RESULTS: A total of 145 (13.8%) were found to be nonimmune. The rate of susceptibility ranged from 3.2% to 25.9% for different age groups. The proportion susceptible was significantly higher at 16.5% in the age group eight to 17 years old versus 3.9% for the age group five to eight years old (χ2=24.08; df=1, P<0.001). There was a significant regression of logarithm titre values on the age of children with an average decline in titre values of 8.1% per annum.CONCLUSIONS: A substantial number of those who were given a single dose of MMR II vaccine may not have protective immunity against rubella as they reach prime reproductive age. There is a definite need to consider a two-dose rubella vaccination strategy in Canada, and these data suggest the second dose given after eight years of age will be most beneficial. In the move towards a routine two-dose measles vaccination strategy in Canada, the MMR II vaccine is being used for the second dose and given either at 18 months of age or at school entry. While this approach will have an overall beneficial effect, the impact of the above timing of the second dose on long term rubella immunity cannot be predicted at this time. These data also underscore the continuing need for prenatal rubella screening program.

scholarly journals Seroconversion rates following COVID-19 vaccination amongst patients with malignant disease- the impact of diagnosis and cancer-directed therapies

2021 ◽  
Author(s):  
Astha Thakkar ◽  
Jesus Gonzalez Lugo ◽  
Niyati Goradia ◽  
Radhika Gali ◽  
Lauren C. Shapiro ◽  
...  
Keyword(s):  
Passive Immunization ◽  
High Rate ◽  
Oncology Patients ◽  
Post Vaccination ◽  
Patients With Cancer ◽  
Immunization Strategies ◽  
Checkpoint Inhibitor Therapy ◽  
Hormonal Therapies ◽  
Anti Cd20 ◽  
The Impact

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post-vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.

scholarly journals Emergence of Unusual Rotavirus G9p[4] and G8p[8] Strains During Post Vaccination Surveillance in Argentina, 2017-2018 

2020 ◽  
Author(s):  
Juan I Degiuseppe ◽  
Juan A Stupka
Keyword(s):  
Early Spring ◽  
High Rate ◽  
Phylogenetic Study ◽  
Genotype Distribution ◽  
Post Vaccination ◽  
Rotavirus Vaccination ◽  
Immunization Strategies ◽  
Monovalent Vaccine ◽  
The Impact ◽  
Children Under 5

Abstract Background. In 2015, Argentina included RotarixTM monovalent vaccine for universal administration and it showed a sharp decline in all-cause and rotavirus-confirmed cases as well as an immediate predominance of the G2P[4] genotype. The aim of this study was to analyze the impact of rotavirus vaccination on disease burden and genotype distribution in our country following its introduction. Methods. Prevalence and seasonality of laboratory-confirmed rotavirus cases data were assessed. Analyses of circulating genotypes were performed by conventional binary characterization (G and P typing). Phylogenetic study of VP7 gene was performed from emergent unusual strains. Results. During 2017-2018, 1183 rotavirus cases (13.2%) were detected and prevalence was uniform among different age subgroups. Weekly distribution showed a raise of confirmed cases around late July and early August. In 2017 the most frequently detected genotypes were G2P[4] and G3P[8]. However, in 2018 G12P[8] genotype increased and it was detected at a high rate. Noteworthy, the detection of uncommon G9P[4] and G8P[8] strains (bearing DS-1-like genetic backbones) was observed at moderate rates. Conclusions. Following four years of this strategy, the prevalence of rotavirus remained low in children under 5 years of age with a shift of the seasonal peak in early spring. The emergence of uncommon genotypes was due to introduction of new strains rather than to reassortment of local strains. Continuous monitoring of rotavirus burden of disease and genotype distribution provides useful evidence to evaluate existing immunization strategies and to contribute in the development of new vaccines as well.

scholarly journals Phycobilins as Potent Food Bioactive Broad-Spectrum Inhibitors Against Proteases of SARS-CoV-2 and Other Coronaviruses: A Preliminary Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Brahmaiah Pendyala ◽  
Ankit Patras ◽  
Chandravanu Dash
Keyword(s):  
Binding Affinity ◽  
Broad Spectrum ◽  
In Silico ◽  
Research Area ◽  
Therapeutic Drug ◽  
Inhibitor Activity ◽  
Current Vaccine ◽  
Mutant Strains ◽  
The Impact

In the 21st century, we have witnessed three coronavirus outbreaks: SARS in 2003, MERS in 2012, and the ongoing pandemic coronavirus disease 2019 (COVID-19). The search for efficient vaccines and development and repurposing of therapeutic drugs are the major approaches in the COVID-19 pandemic research area. There are concerns about the evolution of mutant strains (e.g., VUI – 202012/01, a mutant coronavirus in the United Kingdom), which can potentially reduce the impact of the current vaccine and therapeutic drug development trials. One promising approach to counter the mutant strains is the “development of effective broad-spectrum antiviral drugs” against coronaviruses. This study scientifically investigates potent food bioactive broad-spectrum antiviral compounds by targeting main protease (Mpro) and papain-like protease (PLpro) proteases of coronaviruses (CoVs) using in silico and in vitro approaches. The results reveal that phycocyanobilin (PCB) shows potential inhibitor activity against both proteases. PCB had the best binding affinity to Mpro and PLpro with IC50 values of 71 and 62 μm, respectively. Also, in silico studies with Mpro and PLpro enzymes of other human and animal CoVs indicate broad-spectrum inhibitor activity of the PCB. As with PCB, other phycobilins, such as phycourobilin (PUB), phycoerythrobilin (PEB), and phycoviolobilin (PVB) show similar binding affinity to SARS-CoV-2 Mpro and PLpro.

scholarly journals Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection

2020 ◽  
Author(s):  
Matthew L. Goodwin ◽  
Helen S. Webster ◽  
Hsuan-Yuan Wang ◽  
Jennifer A. Jenks ◽  
Cody S. Nelson ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Cytomegalovirus ◽  
Effector Cell ◽  
Natural Infection ◽  
Congenital Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Domain Specificity ◽  
Cell Functions ◽  
The Impact

AbstractHuman cytomegalovirus (HCMV) is the most common congenital infection, and the leading nongenetic cause of sensorineural hearing loss (SNHL) in newborns globally. A gB subunit vaccine administered with adjuvent MF59 (gB/MF59) is the most efficacious tested to-date, achieving 50% efficacy in preventing infection of HCMV-seronegative mothers. We recently discovered that gB/MF59 vaccination elicited primarily non-neutralizing antibody responses, that HCMV strains acquired by vaccinees more often included strains with gB genotypes that are distinct from the vaccine antigen, and that protection against HCMV acquisition correlated with ability of vaccine-elicited antibodies to bind to membrane associated gB. Thus, we hypothesized that gB-specific non-neutralizing antibody binding breadth and function are dependent on their epitope and genotype specificity as well as their ability to interact with membrane-associated gB. Twenty-four gB-specific monoclonal antibodies (mAbs) isolated from naturally HCMV-infected individuals were mapped for gB domain specificity by binding antibody multiplex assay (BAMA) and for genotype preference binding to membrane-associated gB presented on transfected cells. We defined their non-neutralizing functions including antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC). The isolated gB-specific non-neutralizing mAbs were primarily specific for Domain II and linear antigenic domain 2 site 2 (AD2). We observed variability in mAb gB genotype binding preference, with increased binding to gB genotypes 2 and 4. Functional studies identified two gB-specific mAbs that facilitate ADCP and have binding specificities of AD2 and Domain II. This investigation provides novel understanding on the impact of gB domain specificity and antigenic variability on gB-specific non-neutralizing antibody responses.ImportanceHCMV is the most common congenital infection worldwide, but development of a successful vaccine remains elusive. gB-specific non-neutralizing mAbs, represent a distinct anti-HCMV Ab subset implicated in the protection against primary infection during numerous phase-II gB/MF59 vaccine trials. By studying non-neutralizing gB-specific mAbs from naturally infected individuals, this study provides novel characterization of binding site specificity, genotypic preference, and effector cell functions mediated by mAbs elicited in natural infection. We found that a panel of twenty-four gB-specific non-neutralizing mAbs bind across multiple regions of the gB protein, traditionally through to be targeted by neutralizing mAbs only, and bind differently to gB depending if the protein is soluble versus embedded in a membrane. This investigation provides novel insight into the gB-specific binding characteristics and effector cell functions mediated by non-neutralizing gB-specific mAbs elicited through natural infection, providing new endpoints for future vaccine development.

scholarly journals Evidence for Residual Immunity to Smallpox After Vaccination

2019 ◽  
Vol 34 (s1) ◽  
pp. s129-s129
Author(s):  
Mohana Kunasekaran ◽  
Xin Chen ◽  
Valentina Costantino ◽  
Abrar Chughtai ◽  
Raina MacIntyre
Keyword(s):  
Neutralizing Antibodies ◽  
Immunological Memory ◽  
Evidence Base ◽  
Childhood Vaccination ◽  
Smallpox Vaccination ◽  
Cross Sectional ◽  
Modeling Studies ◽  
Cdc Guidelines ◽  
Duration Of Protection ◽  
The Impact

Introduction:Smallpox has been eradicated, but advances in synthetic biology have increased the risk of its re-emergence. Residual immunity in individuals who were previously vaccinated may mitigate the impact of an outbreak, but there is a high degree of uncertainty regarding the duration and degree of residual immunity.Methods:A systematic literature review using the PRISMA criteria was conducted to quantify the duration and extent of residual immunity to smallpox after vaccination. 29 papers related to quantifying residual immunity to smallpox after vaccination were identified.Results:Duration of protection of >20 years was consistently shown in the 16 retrospective cross-sectional studies, while the lowest estimated duration of protection was 11.7 years among the modeling studies. Childhood vaccination conferred longer duration of protection than vaccination in adulthood. Multiple vaccinations did not appear to improve immunity. Most studies suggest a longer duration of residual immunity (at least 20 years) than assumed in smallpox guidelines. Estimates from modeling studies were less but still greater than the 3-10 years suggested by the WHO Committee on International Quarantine or US CDC guidelines. These recommendations were probably based on observations and studies conducted while smallpox was endemic. The cut-off values for pre-existing antibody levels of >1:20 and >1:32 reported during the period of endemic smallpox circulation may not be relevant to the contemporary population but have been used as a threshold for identifying people with residual immunity in post-eradication era studies.Discussion:Of the total antibodies produced in response to smallpox vaccination, neutralizing antibodies have shown to contribute significantly to immunological memory. Although the mechanism of immunological memory and boosting is unclear, revaccination is likely to result in a more robust response. There is a need to improve the evidence base for estimates on residual immunity to better inform planning and preparedness for re-emergent smallpox.

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