Strategies for Immunomonitoring after Vaccination and during Infection.
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ABSTRACT:
SUBMITTER: Adam L
PROVIDER: S-EPMC8070333 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBreast milk leukocytes may play a role in protecting the infant from pathogens. The dynamics and the role of lymphocytes in human cytomegalovirus (HCMV)-seropositive mothers shedding HCMV into breast milk during the first months postpartum (p.p.) are mostly unclear.MethodsBreast milk cells were analyzed by Pappenheim panoptic and alpha-naphthyl acetate esterase staining as well as by imaging and polychromatic flow cytometry to simultaneously establish their morphological and phenotypic properties. The latter were characterized in HCMV-seropositive and seronegative mothers´ breast milk cells at different time points p.p.ResultsPanoptic staining of breast milk cells revealed the presence of monocytes/macrophages, granulocytes and lymphocytes. Imaging flow cytometry data combining phenotypic and morphological analysis identified NKT-like cells, NK cells, epithelial cells, T cells and monocytes/macrophages. HCMV-seropositive but not -seronegative mothers had significantly higher T cell frequencies in mature milk.ConclusionsThe presence of lymphocyte subsets in breast milk may be more influenced by the HCMV-seropositivity of the mother than previously recognized.
| S-EPMC8462275 | biostudies-literature
Project description:Ongoing research and technology developments hold the promise of rapid production and large-scale deployment of strain-specific or cross-protective vaccines for novel influenza viruses. We sought to investigate the impact of early vaccination on age-specific attack rates and evaluate the outcomes of different vaccination strategies that are influenced by the level of single or two-dose vaccine-induced protections. We developed and parameterized an agent-based model for two population demographics of urban and remote areas in Canada. Our results demonstrate that there is a time period before and after the onset of epidemic, during which the outcomes of vaccination strategies may differ significantly and are highly influenced by demographic characteristics. For the urban population, attack rates were lowest for children younger than 5 years of age in all vaccination strategies. However, for the remote population, the lowest attack rates were obtained for adults older than 50 years of age in most strategies. We found that the reduction of attack rates following the start of vaccination campaigns during the epidemic depends critically on the disease transmissibility, suggesting that for a sufficiently high transmissibility, vaccine delivery after the onset of epidemic has little or no effect, regardless of the population demographics.
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Project description:Human papillomavirus (HPV) is the most common sexually transmitted infection, currently affecting close to 80 million Americans. Importantly, HPV infection is recognized as the etiologic factor for numerous cancers, including cervical, vulval, vaginal, penile, anal, and a subset of oropharyngeal cancers. The prevalence of HPV infection and its associated diseases are a significant problem, affecting millions of individuals worldwide. Likewise, the incidence of HPV infection poses a significant burden on individuals and the broader healthcare system. Between 2011 and 2015, there were an estimated 42,700 new cases of HPV-associated cancers each year in the United States alone. Similarly, the global burden of HPV is high, with around 630,000 new cases of HPV-associated cancer occurring each year. In the last decade, a total of three preventive major capsid protein (L1) virus-like particle-based HPV vaccines have been licensed and brought to market as a means to prevent the spread of HPV infection. These prophylactic vaccines have been demonstrated to be safe and efficacious in preventing HPV infection. The most recent iteration of the preventive HPV vaccine, a nanovalent, L1-VLP vaccine, protects against a total of nine HPV types (seven high-risk and two low-risk HPV types), including the high-risk types HPV16 and HPV18, which are responsible for causing the majority of HPV-associated cancers. Although current prophylactic HPV vaccines have demonstrated huge success in preventing infection, existing barriers to vaccine acquisition have limited their widespread use, especially in low- and middle-income countries, where the burden of HPV-associated diseases is highest. Prophylactic vaccines are unable to provide protection to individuals with existing HPV infections or HPV-associated diseases. Instead, therapeutic HPV vaccines capable of generating T cell-mediated immunity against HPV infection and associated diseases are needed to ameliorate the burden of disease in individuals with existing HPV infection. To generate a cell-mediated immune response against HPV, most therapeutic vaccines target HPV oncoproteins E6 and E7. Several types of therapeutic HPV vaccine candidates have been developed including live-vector, protein, peptide, dendritic cell, and DNA-based vaccines. This chapter will review the commercially available prophylactic HPV vaccines and discuss the recent progress in the development of therapeutic HPV vaccines.
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Project description:BackgroundAs SARS-CoV-2 vaccines are administered worldwide, the COVID-19 pandemic continues to exact significant human and economic costs. Mass testing of unvaccinated individuals followed by isolation of positive cases can substantially mitigate risks and be tailored to local epidemiological conditions to ensure cost effectiveness.MethodsUsing a multi-scale model that incorporates population-level SARS-CoV-2 transmission and individual-level viral load kinetics, we identify the optimal frequency of proactive SARS-CoV-2 testing, depending on the local transmission rate and proportion immunized.FindingsAssuming a willingness-to-pay of US$100,000 per averted year of life lost (YLL) and a price of $10 per test, the optimal strategy under a rapid transmission scenario (Re ∼ 2.5) is daily testing until one third of the population is immunized and then weekly testing until half the population is immunized, combined with a 10-day isolation period of positive cases and their households. Under a low transmission scenario (Re ∼ 1.2), the optimal sequence is weekly testing until the population reaches 10% partial immunity, followed by monthly testing until 20% partial immunity, and no testing thereafter.InterpretationMass proactive testing and case isolation is a cost effective strategy for mitigating the COVID-19 pandemic in the initial stages of the global SARS-CoV-2 vaccination campaign and in response to resurgences of vaccine-evasive variants.FundingUS National Institutes of Health, US Centers for Disease Control and Prevention, HK Innovation and Technology Commission, China National Natural Science Foundation, European Research Council, and EPSRC Impact Acceleration Grant.
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Project description:Vaccination against cancer-associated antigens has long held the promise of inducting potent antitumor immunity, targeted cytotoxicity while sparing normal tissues, and long-lasting immunologic memory that can provide surveillance against tumor recurrence. Evaluation of vaccination strategies in preclinical brain tumor models has borne out the capacity for the immune system to effectively and safely eradicate established tumors within the central nervous system. Early phase clinical trials have established the feasibility, safety, and immunogenicity of several vaccine platforms, predominantly in patients with glioblastoma. Definitive demonstration of clinical benefit awaits further study, but initial results have been encouraging. With increased understanding of the stimulatory and regulatory pathways that govern immunologic responses and the enhanced capacity to identify novel antigenic targets using genomic interrogation of tumor cells, vaccination platforms for patients with malignant brain tumors are advancing with increasing personalized complexity and integration into combinatorial treatment paradigms.
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Project description:The epidemic emergence of Zika virus (ZIKV) in 2015-2016 has been associated with congenital malformations and neurological sequela. Current efforts to develop a ZIKV vaccine build on technologies that successfully reduced infection or disease burden against closely related flaviviruses or other RNA viruses. Subunit-based (DNA plasmid and modified mRNA), viral vectored (adeno- and measles viruses) and inactivated viral vaccines are already advancing to clinical trials in humans after successful mouse and non-human primate studies. Among the greatest challenges for the rapid implementation of immunogenic and protective ZIKV vaccines will be addressing the potential for exacerbating Dengue virus infection or causing Guillain-Barré syndrome through production of cross-reactive immunity targeting related viral or host proteins. Here, we review vaccine strategies under development for ZIKV and the issues surrounding their usage.
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Project description:A novel statistical model based on a two-layer, contact and information, graph is suggested in order to study the influence of disease prevalence on voluntary general population vaccination during the COVID-19 outbreak. Details about the structure and number of susceptible, infectious, and recovered/vaccinated individuals from the contact layer are simultaneously transferred to the information layer. The ever-growing wealth of information that is becoming available about the COVID virus was modelled at each individual level by a simplified proxy predictor of the amount of disease spread. Each informed individual, a node in a heterogeneous graph, makes a decision about vaccination "motivated" by their benefit. The obtained results showed that disease information type, global or local, has a significant impact on an individual vaccination decision. A number of different scenarios were investigated. The scenarios showed that in the case of the stronger impact of globally broadcasted disease information, individuals tend to vaccinate in larger numbers at the same time when the infection has already spread within the population. If individuals make vaccination decisions based on locally available information, the vaccination rate is uniformly spread during infection outbreak duration. Prioritising elderly population vaccination leads to an increased number of infected cases and a higher reduction in mortality. The developed model accuracy allows the precise targeting of vaccination order depending on the individuals' number of social contacts. Precisely targeted vaccination, combined with pre-existing immunity, and public health measures can limit the infection to isolated hotspots inside the population, as well as significantly delay and lower the infection peak.
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Project description:The coronavirus disease 2019 (COVID-19) is caused by the infection of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the novel coronavirus. In most countries, the containment of this virus spread is not controlled, which is driving the pandemic towards a more difficult phase. In this study, we investigated the impact of the Bacille Calmette Guerin (BCG) vaccination on the severity and mortality of COVID-19 by performing transcriptomic analyses of SARS-CoV-2 infected and BCG vaccinated samples in peripheral blood mononuclear cells (PBMC). A set of common differentially expressed genes (DEGs) were identified and seeded into their functional enrichment analyses via Gene Ontology (GO)-based functional terms and pre-annotated molecular pathways databases, and their Protein-Protein Interaction (PPI) network analysis. We further analysed the regulatory elements, possible comorbidities and putative drug candidates for COVID-19 patients who have not been BCG-vaccinated. Differential expression analyses of both BCG-vaccinated and COVID-19 infected samples identified 62 shared DEGs indicating their discordant expression pattern in their respected conditions compared to control. Next, PPI analysis of those DEGs revealed 10 hub genes, namely ITGB2, CXCL8, CXCL1, CCR2, IFNG, CCL4, PTGS2, ADORA3, TLR5 and CD33. Functional enrichment analyses found significantly enriched pathways/GO terms including cytokine activities, lysosome, IL-17 signalling pathway, TNF-signalling pathways. Moreover, a set of identified TFs, miRNAs and potential drug molecules were further investigated to assess their biological involvements in COVID-19 and their therapeutic possibilities. Findings showed significant genetic interactions between BCG vaccination and SARS-CoV-2 infection, suggesting an interesting prospect of the BCG vaccine in relation to the COVID-19 pandemic. We hope it may potentially trigger further research on this critical phenomenon to combat COVID-19 spread.
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Project description:Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a major global healthcare problem with more than 240 million and 70 million infected, respectively. Both viruses persist within the liver and result in progressive liver disease, resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma. Strikingly, this pathogenesis is largely driven by immune responses, unable to clear an established infection, rather than by the viral pathogens themselves. Even though disease progression is very similar in both infections, HBV and HCV have evolved distinct mechanisms, by which they ensure persistence within the host. Whereas HCV utilizes a cloak-and-dagger approach, disguising itself as a lipid-like particle and immediately crippling essential pattern-recognition pathways, HBV has long been considered a "stealth" virus, due to the complete absence of innate immune responses during infection. Recent developments and access to improved model systems, however, revealed that even though it is among the smallest human-tropic viruses, HBV may, in addition to evading host responses, employ subtle immune evasion mechanisms directed at ensuring viral persistence in the absence of host responses. In this review, we compare the different strategies of both viruses to ensure viral persistence by actively interfering with viral recognition and innate immune responses.
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Project description:Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization. Additionally, RSV is responsible for 10,000 deaths annually among the elderly across the United States, and accounts for nearly as many hospitalizations as influenza. Currently, several RSV vaccine candidates are under development to target different age groups. To evaluate the potential effectiveness of age-specific vaccination strategies in averting RSV incidence, we developed a transmission model that integrates data on daily infectious viral load and changes of behavior associated with RSV symptoms. Calibrating to RSV weekly incidence rates in Texas, California, Colorado, and Pennsylvania, we show that in all states considered, an infected child under 5 y of age is more than twice as likely as a person over 50 y of age to transmit the virus. Geographic variability in the effectiveness of a vaccination program across states arises from interplay between seasonality patterns, population demography, vaccination uptake, and vaccine mechanism of action. Regardless of these variabilities, our analysis showed that allocating vaccine to children under 5 y of age would be the most efficient strategy per dose to avert RSV in both children and adults. Furthermore, due to substantial indirect protection, the targeting of children is even predicted to reduce RSV in the elderly more than directly vaccinating the elderly themselves. Our results can help inform ongoing clinical trials and future recommendations on RSV vaccination.
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