Fast DNA Vaccination Strategy Elicits a Stronger Immune Response Dependent on CD8+CD11c+ Cell Accumulation

Conventional DNA vaccine strategies usually employ a regimen of immunizations at 2-week or longer intervals to induce effective memory cell-dependent immune responses. Clinical cancer treatment requires a faster immunization strategy to contend with tumor progression. In this study, a novel fast immunization strategy was established, wherein a DNA vaccine was intramuscularly administered on days 0, 2, and 5 in a murine lung cancer model. Effector cells peaked 7 to 10 days after the last vaccination. Compared with traditional 2-week-interval immunization strategies, antigen-specific cytolysis and INF-γ secretion were significantly enhanced under the fast vaccination approach. As a result, the rapidly administered DNA vaccine elicited stronger and more prompt antitumor effects. The probable underlying mechanism of fast immunization was the accumulation of CD8+CD11c+ antigen-presenting cells at the injection site, which enhanced subsequent antigen presentation. In conclusion, the fast DNA vaccination strategy shortened vaccination time to 5 days and elicited a stronger antitumor immune response.

Evaluation of the discriminatory potential of antibodies created from synthetic peptides derived from wheat, barley, rye and oat gluten

Celiac disease (CD) is triggered by ingestion of gluten-containing cereals such as wheat, barley, rye and in some cases oat. The only way for affected individuals to avoid symptoms of this condition is to adopt a gluten-free diet. Thus, gluten-free foodstuffs need to be monitored in order to ensure their innocuity. For this purpose, commercial immunoassays based on recognition of defined linear gluten sequences are currently used. These immunoassays are designed to detect or quantify total gluten regardless of the cereal, and often result in over or underestimation of the exact gluten content. In addition, Canadian regulations require a declaration of the source of gluten on the label of prepackaged foods, which cannot be done due to the limitations of existing methods. In this study, the development of new antibodies targeting discrimination of gluten sources was conducted using synthetic peptides as immunization strategy. Fourteen synthetic peptides selected from unique linear amino acid sequences of gluten were bioconjugated to Concholepas concholepas hemocyanin (CCH) as protein carrier, to elicit antibodies in rabbit. The resulting polyclonal antibodies (pAbs) successfully discriminated wheat, barley and oat prolamins during indirect ELISA assessments. pAbs raised against rye synthetic peptides cross-reacted evenly with wheat and rye prolamins but could still be useful to successfully discriminate gluten sources in combination with the other pAbs. Discrimination of gluten sources can be further refined and enhanced by raising monoclonal antibodies using a similar immunization strategy. A methodology capable of discriminating gluten sources, such as the one proposed in this study, could facilitate compliance with Canadian regulations on this matter. This type of discrimination could also complement current immunoassays by settling the issue of over and underestimation of gluten content, thus improving the safety of food intended to CD and wheat-allergic patients.

Cost-Effectiveness of Hepatitis B Mass Screening and Management in High-Prevalent Rural China: A Model Study From 2020 to 2049

Background: Chronic hepatitis B is highly prevalent among adults in rural China and better management of those populations is of vital importance for viral hepatitis elimination. Adult immunization has been the subject of much controversy in previous studies. This study estimates the cost-effectiveness of population-based hepatitis B screening, treatment, and immunization strategy (comprehensive strategy) in rural areas with high prevalence under the national policy of sharp-drop drug prices. Methods: We constructed a Markov model comparing 4 strategies in a 30-year horizon from the healthcare payer perspective: (1) the conventional pattern; (2) screening and treating infected (treatment); (3) screening and immunizing susceptible individuals (immunization); and (4) the comprehensive strategy. Screening intensity ranged from 50% to 100%. Outcomes were measured by costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and clinical outcomes. Results: The costs for the conventional pattern, treatment strategy, immunization strategy, and comprehensive strategy were US$ 341, 351, 318, and 323, respectively. In addition, effects were 17.45, 17.57, 17.46, and 17.58 QALYs, respectively. The ICER of the comprehensive strategy was 35 US$/QALY gained at 50% screening intensity and 420 US$/QALY gained at 100%. The net monetary benefit increased with increasing screening intensity and declined after 90%, with the highest value of US$ 40693. All new infections and 52.5% mortality could be avoided from 2020 to 2049 if all patients were properly treated and all susceptible individuals were immunized. The results were stable within a wide range of parameters. Conclusions: It was cost-effective to implement the mass hepatitis B screening, treatment, and immunization strategy in areas of rural China with high prevalence, and the strategy gained the most net monetary benefit at a screening intensity of 90%. Although it was impractical to fulfill 100% coverage, efforts should be made to obtain more people screened.

The research on propagation modeling and governance strategies of online rumors based on behavior–attitude

PurposeThe purpose of this paper is to achieve effective governance of online rumors through the proposed rumor propagation model and immunization strategy.Design/methodology/approachThe paper leverages the agent-based modeling (ABM) method to model individuals from two aspects, behavior and attitude. Based on the analysis and research of online data, we propose a rumor propagation model, namely the Untouched view transmit removed-Susceptible hesitate agree disagree (Unite-Shad), and devise an immunization strategy, namely the Gravity Immunization Strategy (GIS). A graph-based framework, namely Pregel, is used to carry out the rumor propagation simulation experiments. Through the experiments, the rationality of the Unite-Shad and the effectiveness of the GIS are verified.FindingsThe study discovers that the inconsistency between human behaviors and attitudes in rumor propagation can be explained by the Unite-shad model. Besides, the GIS, which shows better performance in small-world networks than in scale-free networks, can effectively suppress rumor propagation in the early stage.Research limitations/implicationsThis paper provides an effective immunization strategy for rumor governance. Specifically, the Unite-Shad model reveals the mechanism of rumor propagation, and the GIS provides an effective governance method for selecting immune nodes.Originality/valueThe inconsistency of human behaviors and attitudes in real scenes is modeled in the Unite-Shad model. Combined with the model, the definition of diffusion domain is proposed and a novel immunization strategy, namely GIS, is designed, which is significant for the social governance of rumor propagation.

Heterologous vaccination strategy for containing COVID-19 pandemic

An unequitable vaccine allocation and continuously emerging SARS-CoV-2 variants pose challenges to contain the pandemic, which underscores the need for licensing more vaccine candidates, increasing manufacturing capacity and implementing better immunization strategy. Here, we report data from a proof-of-concept investigation in two healthy individuals who received two doses of inactivated whole-virus COVID-19 vaccines, followed by a single heterologous boost vaccination after 7 months with an mRNA vaccine candidate (LPP-Spike-mRNA) developed by Stemirna Therapeutics. Following the boost, Spike-specific antibody (Ab), memory B cell and T cell responses were significantly increased. These findings indicate that a heterologous immunization strategy combining inactivated and mRNA vaccines can generate robust vaccine responses and therefore provide a rational and effective vaccination regimen.