Immunostimulant Research Articles

The health profile of Lithuanian beekeepers and use of bee products for health purposes

Abstract Background There is little research about the health profile and attitude of beekeepers themselves who are the main suppliers of apitherapy products to the general public. The study aims to describe the health profile of Lithuanian bee keepers and identify their attitudes towards use of bee products for health purposes. Methods A cross-sectional survey was carried out from November 2023 to February 2024 among beekeepers in Lithuania. A representative sample of N = 369 (5% margin of error) has been enrolled in the study. A mixed-model approach was used for data collection. Research instrument consisted of a two-part questionnaire covering socio-demographic variables and questions on the use of bee products. Results 369 respondents participated in the study: 73% (n = 270) males and 27% (n = 99) of females. The mean age was 57.8 years (SD = 14.4). Beekeepers assessed their health as good and only 2% assessed it as bad, while the Lithuanian rate is 12%. 95% of the respondents used bee products for health purposes, 5% did not use at all. Large beekeepers (>100 beehives) were more likely not to choose bee products (p < 0.001). No correlation was found between chronic diseases and consumption of bee products, except for diabetes mellitus (p = 0.001). The most common reasons for choosing apitherapy products included respiratory (62%), digestive (31%) diseases, immunity boosting (77%), dermatological conditions (53%). Propolis was pointed out in the survey as being used by 74%. Elder beekeepers (>65 years) were found to be more likely to use propolis (p < 0.001). They were also more likely to use it for prevention (p < 0.001) and in case of toothache (p = 0.001). Conclusions The majority of beekeepers use bee products for health purposes. The most common reasons for consuming honey and other bee products are immunity boosting and colds. It was found that beekeepers over 65 years of age are more likely to use propolis for prevention and toothache treatment. Key messages • Although the consumption of bee products is high among beekeepers, elder generation and owners of smaller apiaries are more likely to use bee products for health purposes. • Chronic diseases are not associated with consumption of bee products, except for beekeepers with diabetes mellitus who do not consume it.

A generic cell-based biosensor converts bacterial infection signals into chemoattractants for immune cells.

Bacterial infections are a major challenge to human health. Although various potent antibiotics have emerged in the last decades, current challenges arise from an increasing number of multi-drug-resistant species. Infections associated with implants represent a particular challenge since they are usually diagnosed at an advanced state, and are difficult to treat with antibiotics due to the formation of protecting biofilms. In this study, we designed and explored a synthetic biology-inspired, cell-based bio-sensor/actor for the detection and counteraction of bacterial infections. The system is generic as it senses diverse types of infections and acts by enhancement of the endogenous immune system. The strategy is based on genetically engineered sensor/actor cells that can sense type I interferons (IFNs), which are released by immune cells at the early stages of infections. IFN signalling activates a synthetic circuit to induce reporter genes with a sensitivity of only 5 pg/ml of IFN and leads to a therapeutic protein output of 100ng/ml, resulting in theranostic cells that visualize and fight infections. Robustness and resilience were achieved by the implementation of a positive feedback loop. We show that diverse gram-positive and gram-negative implant-associated pathogenic bacteria activate the cascade in co-culture systems in a dose-dependent manner. Finally, we show that this system can be used to secrete chemoattractants facilitating the infiltration of immune cells in response to bacterial triggers. Together, the system is not only universal to bacterial infections but at the same time hypersensitive allowing the sensing of infections at initial stages.

Neutralizing Antibody-Mediated Protection from Prior Delta Variant Infection Against Omicron BA.5 Sub-Lineage Reinfection One Year Later: A Prospective Cohort Study

Background: Previous SARS-CoV-2 infection provides some level of protection against reinfection. However, few studies have evaluated the neutralizing antibody (NAb) response after Delta variant infection and its ability to prevent reinfection with Omicron BA.5 one year later. Methods: This prospective cohort study included 431 patients who recovered from Delta variant infection. We measured their serum NAb titers against both Delta and Omicron BA.5 using microneutralization tests. Results: Over a 17-month follow-up, 17.9% of the participants were reinfected with Omicron BA.5. Younger adults (18–65 years) and individuals who did not receive booster immunization had significantly higher reinfection rates than older adults (>65 years) and those who received boosters (p < 0.05). Notably, reinfection rates were higher in post-vaccination breakthrough cases than in individuals who were naturally infected. However, booster immunization reduced reinfection rates within the breakthrough group. We found no significant association between Delta NAb levels and protection against Omicron BA.5 reinfection (p > 0.05). Cross-neutralization assays showed a 7.1-fold reduction in NAb efficacy against Omicron BA.5. Conclusions: Delta-variant infection-induced NAbs did not strongly predict protection against Omicron BA.5 reinfection. However, booster immunization effectively reduced the reinfection rate approximately one year after the initial Delta infection.

Eco-Friendly Analytical Approach for Sensitive Spectrofluorimetric Determination of the Flavonoid Chrysin in Capsules and Human Plasma.

Chrysin is a plant flavonoid that has different therapeutic effects as anti-inflammatory, anti-cancer, anti-oxidant, and immune booster. Spectrofluorimetry has received a lot of interest lately because of itsecological greenness and analytical performance. This approach employed the native fluorescence of chrysin at 339nm following excitation at 231nm in distilled water. Modern advances in analytical chemistry have been used to lessen occupational and environmental concerns by employing distilled water as a dilution solvent throughmethod development and application. The approach was found to be excellent green supported byeco-scale score of 97and 0.94AGREErating, in addition to an overall whiteness score of 88.80. The design aimed to analyze chrysin in raw materials, Chrysin® capsules and human plasma. The method was linear over0.5-7.0ngmL⁻1 chrysin, with LOD of 0.06ngmL⁻1 and LOQ of 0.20ngmL⁻1. The offered methodwas effectively applied for determination of chrysin inthe commercial capsules Chrysin® and spiked human plasma samples with average recoveries of 99.76%and 99.98%, respectively for capsules andspiked human plasma. Up to date, no spectrofluorimetric method has been described for chrysin analysis, then, this presented an opportunity to develop a sensitive, quick, reliable, environmentally friendly, and valid fluorescence-based method.

Advanced optimal control approaches for immune boosting and clinical treatment to enhance dengue viremia models using ABC fractional-order analysis

IntroductionThis work focuses on the Dengue-viremia ABC (Atangana-Baleanu Caputo) fractional-order differential equations, accounting for both symptomatic and asymptomatic infected cases. Symptomatic cases are characterized by higher viremia levels, whereas asymptomatic cases exhibit lower viremia levels. The fractional-order model highlights memory effects and other advantages over traditional models, offering a more comprehensive representation of dengue dynamics.MethodsThe total population is divided into four compartments: susceptible, asymptomatic infected, symptomatic infected, and recovered. The model incorporates an immune-boosting factor for asymptomatic infected individuals and clinical treatment for symptomatic cases. Positivity and boundedness of the model are validated, and both local and global stability analyses are performed. The novel Adams-Bash numerical scheme is utilized for simulations to rigorously assess the impact of optimal control interventions.ResultsThe results demonstrate the effectiveness of the proposed control strategies. The reproduction numbers must be reduced based on specific optimal control conditions to effectively mitigate disease outbreaks. Numerical simulations confirm that the optimal control measures can significantly reduce the spread of the disease.DiscussionThis research advances the understanding of Dengue-viremia dynamics and provides valuable insights into the application of ABC fractional-order analysis. By incorporating immune-boosting and clinical treatment into the model, the study offers practical guidelines for implementing successful disease control strategies. The findings highlight the potential of using optimal control techniques in public health interventions to manage disease outbreaks more effectively.

Evaluation of Echinacea purpurea Extracts as Immunostimulants: Impact on Macrophage Activation.

Echinacea purpurea has been traditionally used to strengthen the immune system. Therefore, herein, we investigated the potential of E. purpurea aqueous extracts (AEs) obtained from flowers (F), leaves (L), or roots (R) as an immune booster in human primary monocyte-derived macrophages (hMDMs). Additionally, to identify the main class of compounds (phenolic/carboxylic acids vs. alkylamides) responsible for the bioactivity, the three AEs were fractioned by semi-preparative high-performance liquid chromatography (HPLC). The AEs and the isolated phenolic/carboxylic acidic fractions were not cytotoxic for hMDMs for all tested concentrations, as confirmed by the metabolic activity and DNA content assays. Moreover, AE drastically induced the production of the interleukin (IL)-6 and tumor necrosis factor (TNF)-α, with a minimal effect on IL-1β and prostaglandin E2 (PGE2), supporting their potential for macrophage activation. Interestingly, in the presence of the phenolic/carboxylic acidic fractions, this efficacy considerably decreased, suggesting a complementary effect between compounds. AE also triggered the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling pathways and upregulated the cyclooxygenase (COX)-2 expression in hMDMs. Overall, AE-F was demonstrated to be the most powerful immunostimulant extract that can be related to their higher number in identified bioactive compounds compared to AE-L and AE-R. These results highlight the efficiency of E. purpurea AE to enhance the function of a key cell type of the immune system and their potential as immunostimulant formulations for patients with a compromised immune system due to certain diseases (e.g., acquired immunodeficiencies) and treatments (e.g., chemotherapy).

Programmable Circular Multivalent Nanobody‐Targeting Chimeras (mNbTACs) for Multireceptor‐Mediated Protein Degradation and Targeted Drug Delivery

Multispecific therapeutics hold significant promise in drug delivery, protein degradation, and cell recruitment to address clinical issues of tumor heterogeneity, resistance, and immune evasion. However, their modular engineering remains challenging. We developed a targeted degradation platform, termed multivalent nanobody‐targeting chimeras (mNbTACs), by encoding diverse nanobody codons on a circular template using DNA printing technology. The homo‐ or hetero‐ mNbTACs specifically recognized membrane targets in a multivalent manner and simultaneously recruited scavenger receptors to favor clathrin‐/caveolae‐dependent endocytosis and lysosomal degradation of multiple proteins with high efficiency and selectivity. We demonstrated that a bispecific doxorubicin‐loaded mNbTAC, named Doxo‐mvNbsPPH, passively accumulated at tumor sites, specifically interacted with PD‐L1 and HER2 targets, and was rapidly transported into lysosome, inducing potent immunogenic cell death and alleviating immune checkpoint evasion. The synergistic boosting of innate and adaptive immunity promoted the infiltration and proliferation of CD8+ T cells in tumor microenvironment (an 11‐fold increase) with high toxicity and low exhaustion, eventually enhancing antitumor efficacy. Our mNbTAC platform provides multispecific therapeutics with variable valences and programmed species, whereas it induces targeted protein degradation through multireceptor‐mediated endocytosis and lysosomal degradation without the need for lysosome‐targeting receptors, representing a general and modular tool to harness extracellular proteome for disease treatment.

Programmable Circular Multivalent Nanobody-Targeting Chimeras (mNbTACs) for Multireceptor-Mediated Protein Degradation and Targeted Drug Delivery.

Multispecific therapeutics hold significant promise in drug delivery, protein degradation, and cell recruitment to address clinical issues of tumor heterogeneity, resistance, and immune evasion. However, their modular engineering remains challenging. We developed a targeted degradation platform, termed multivalent nanobody-targeting chimeras (mNbTACs), by encoding diverse nanobody codons on a circular template using DNA printing technology. The homo- or hetero- mNbTACs specifically recognized membrane targets in a multivalent manner and simultaneously recruited scavenger receptors to favor clathrin-/caveolae-dependent endocytosis and lysosomal degradation of multiple proteins with high efficiency and selectivity. We demonstrated that a bispecific doxorubicin-loaded mNbTAC, namedDoxo-mvNbsPPH, passively accumulated at tumor sites, specifically interacted with PD-L1and HER2targets, and was rapidly transported into lysosome, inducing potent immunogenic cell death and alleviating immune checkpoint evasion. The synergistic boosting of innate and adaptive immunity promoted the infiltration and proliferation of CD8+T cells in tumor microenvironment (an 11-fold increase) with high toxicity and low exhaustion, eventually enhancing antitumor efficacy. Our mNbTAC platform provides multispecific therapeutics with variable valences and programmed species, whereas it induces targeted protein degradation through multireceptor-mediated endocytosis and lysosomal degradation without the need for lysosome-targeting receptors, representing a general and modular tool to harness extracellular proteome for disease treatment.

Physicochemical and Antioxidative Properties of Protein Hydrolysates from Residual Goat Placenta Extract by Two Different Methods.

Protein hydrolysates from the goat placenta provide multiple benefits, such as immune system enhancement, antioxidant activities, and reductions in uric acid levels. Despite these benefits, their industrial applications have been underexplored. This study aimed to prepare extract protein hydrolysates (GPERPs) from residual goat placenta extract (GPER) and assess their functional properties, focusing on how different drying methods influence these properties. The essential amino acid contents were 30.94% for the GPER and 34.11% for the GPERPs. Moreover, all the essential amino acids were present, and the amino acid score (AAS) for each exceeded 1.0 in the GPERPs. The foaming properties of the spray-dried GPERPs (95.56 ± 5.89%) were significantly greater than those of the freeze-dried GPERPs (49.13 ± 4.17%) at pH values of 4.0~10.0. The emulsion stability (ES) of the spray-dried GPERPs (453.44 ± 8.13 min) was notably greater than that of the freeze-dried GPERPs (245.58 ± 7.12 min). Furthermore, the water retention capacity (WRC) of the freeze-dried GPERPs (201.49 ± 6.12%) was significantly greater than that of the spray-dried GPERPs (103.35 ± 7.13%), except at pH 10.0 (101.44 ± 8.13%). Similarly, at pH values of 6.0, 8.0, and 10.0, the oil retention capacity (ORC) of the freeze-dried GPERPs (715.58 ± 12.15%) was significantly greater than that of the spray-dried GPERPs (560.56 ± 11.15%), although the opposite trend was noted under acidic conditions. In terms of the antioxidant activity, the ability of the goat placenta extract residual protein hydrolysates (GPERPs) to scavenge DPPH radicals and superoxide anion radicals increased with the increasing peptide powder concentration, and the maximum scavenging rates of the DPPH radicals (39.5 ± 0.56%) and superoxide anions (81.2 ± 0.54%) in the freeze-dried peptide powder were greater than those in the spray-dried peptide powder. These findings contribute to the understanding of the physicochemical and antioxidant properties of GPERPs under various drying methods and provide fundamental data for the development of functional foods based on GPERPs.

Recycled lithium battery nanomaterials as a sustainable nanofertilizer: Reduced peanut allergenicity and improved seed quality

The rapidly increasing amount of end-of-life lithium iron phosphate (LiFePO4) batteries has raised significant environmental concerns. This study offers a strategy for a paradigm shift by transforming this growing waste into a valuable resource by recycling discarded LiFePO4 batteries and safely integrating the materials into sustainable agriculture. We used five types of LiFePO4 (10, 50 mg kg−1) applied to soil planted with peanuts in a full-culture experiment. Our results show that addition of <50 mg kg−1 of recycled nano-LiFePO4 (rn-LiFePO4) has a multifaceted positive impact on peanut because of sustainable release of nutrients and nano-specific effects, not only enhancing photosynthesis and root growth but also increasing yield by 22 %–34 % while simultaneously elevating seed nutritional quality. Moreover, a remarkable reduction (up to 99.78 % at 10 mg kg−1 rn-LiFePO4) in the expression of allergen genes was evident following exposure to LiFePO4, which showed a significant negative correlation with Fe content in the seeds. The decreased peanut allergen gene expression was mediated by a downregulation of metabolites associated with protein digestion and absorption. Furthermore, rhizosphere soil immune system enhancement may indirectly enhance immune responses to peanut allergy. This study suggests the significant potential of nanoscale LiFePO4 recycled from Li battery, including enhancing crop yield quality and mitigating peanut allergy concerns while simultaneously addressing a growing waste stream of concern.

Effect of Phyto Constitutes of &lt;i&gt;Ayurveda&lt;/i&gt; and &lt;i&gt;Siddha&lt;/i&gt; Herbs on SARS-CoV-2/CoVID-19 Management by Modulating the Human Gut Microbiome

The therapeutic plants used in Ayurveda and Siddha medicine primarily function as immunomodulators to combat viral infection. The majority of the Indian states adopted an integrative approach to the treatment strategy for COVID-19 infection during the COVID-19 outbreak. A large percentage of Indians consume Ayurvedic and Siddha herbs as preventative medication or immune boosters during the COVID outbreak. ACE-2 receptor, Mpro, Nsp15, endoribonuclease, ACE-2-RBD interface, RBD complex, helicase inhibitors, and ACE-2-RBD interface are the main targets of the phytochemicals of medicinal plants, which also have the potential to limit their action and lower infection rates. The phytonutrients also preserve the permeability of the gut epithelial membrane and improve gut barrier proteins including occludin, Zo-1, and claudin. The phytonutrients also help probiotic bacteria flourish, such as Faecalibacterium, Rikenellaceae, Lactobacillus and Lachnospiraceae, which may lower proinflammatory cytokines and improve immunological function. A small number of opportunistic bacteria, such as Pseudomonas aeruginosa and Klebsiella pneumonia, co-infect with the SARS-CoV-2 virus and increase the frequency of hospital stays and severity of the illness. The co-infections or secondary infections may be reduced by the antibacterial and anti-inflammatory activities of phytochemicals.

The Effect of Fermented Wheat Germ Extract on Broiler Chicks’ Growth Performance, Immunological Status, and Carcass Characteristics

Abstract Many studies have mentioned the advantages of adding wheat germ to chicken diets, but few were interested in studying the effect of the fermentation process on this addition. The present study aimed to investigate the effects of adding fermented wheat germ extract (FWGE) and immunostimulant (IS) to the broiler diet and water, respectively, on growth performance, hematological and blood biochemical parameters, immune status, and carcass characteristics. A total of 180 one-day-old broiler chicks (Cobb 500) were randomly and equally assigned into four treatment groups of 5 replicates (9 chicks/replicate) each. The first group (G1) served as a control group with a basal diet and normal drinking water, while the second (G2) and the third (G3) groups were treated with a basal diet supplemented with 0.1 and 0.2% of FWGE, respectively. The fourth group (G4) was treated with one level of immunostimulant (ORGA IMMU®, 0.2% in drinking water) and served as a positive control. The experiment lasted 35 days. According to the results, adding 0.2% FWGE to the broiler diet (G3) improved (P≤0.05) feed conversion ratio and increased (P≤0.05) live body weight and body weight gain compared to the control group (G1). The G3 also showed improvements (P≤0.05) in red blood cells (RBCs), hemoglobin concentration (Hb), packed cell volume (PCV), and white blood cell (WBC) counts. Blood biochemical parameters, such as total protein, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were positively affected (P≤0.05) by FWGE and immunostimulant treatments. Hemagglutination inhibition (HI) titers for Newcastle disease and avian influenza viruses, phagocytic activity (PA), phagocytic index (PI), and lysozyme activity (LA) were significantly (P≤0.05) improved by FWGE and immunostimulant treatments. Furthermore, carcass traits, such as carcass weight and dressing percentage, were improved (P≤0.05) by adding FWGE and immunostimulant treatments. The inclusion of FWGE in the broiler chicken diet by 0.2% had a considerably positive impact on the birds’ growth performance, health, and carcass quality.

Green synthesis of carbon dots nanoparticles from edible swiftlet nest and evaluation of their antioxidant activity

Edible swiftlet nest (ESN) confers various health benefits to humans, including immune system enhancement, anti-inflammatory properties, bone strengthening, and antioxidative effect. ESN is notably rich in protein and minerals, with its proteins serving as non-enzymatic antioxidants capable of binding free radicals. However, the antioxidant capacity of ESN is comparatively lower than that of other free radical scavengers, such as carbon dots nanoparticles (CNPs). CNPs features charged ligands on their surface that act as electron donors for free radical binding. The presence of the carbon chain forming proteins in ESN suggests their potential as the primary source for CNPs formation. The enhancement of hydroxyl groups and delocalized electrons is imperative for enhancing the antioxidant activity of ESN. This study aims to enhance the antioxidant activity of ESN by converting it into CNPs nanoparticles. The results demonstrated the effective synthesis of CNPs from the ESN solution using microwave methods. This was evidenced by XRD patterns indicating CNPs formation, and an average particle size of 4.86 nm as indicated by TEM analysis. The optimal microwave heating duration of 30 min yielded CNPs with a prominent emission spectrum peak at 425 nm and significantly high intensity. Absorbance data revealed the presence of C=C bonds, consistent with aromatic CNPs bonds observed in FTIR studies. CNPs possessed hydroxyl and carboxyl linkages, suggesting their potential as antioxidants. The percent inhibition results indicated that CNPs exhibited a substantial percentage (62.5%) at a concentration of 50 mg ml−1. The free radical scavenging activity of the CNPs significantly elevated compared to ESN.

Dabur Chyawankidz Gummies: A novel dosage form for immunomodulation

Across age groups, a tasty eatable product is always cherished and so is immunity on the other hand, equally indispensable throughout lifetime. Optimal and sustained immunity is a contiguous requirement for growth and welfare of the body and goodness of herbs of Chyawanprash is a time-tested formula in Ayurveda for a healthy life. Combining the innovation of a chewable system of drug delivery with goodness of Ayurveda, Dabur India Limited has prepared the Dabur ChyawanKidz Gummies – a palatable, chewable and immune boosting formulation. To assess its efficacy, the active immune boosting formulation of the product were studied for its activity on NK Cell, Cytokines (TNF-α) and phagocytosis by Macrophages; wherein compared to the control groups, the test product showed up to 49% increased NK Cell activity, 66-fold increase in TNF-α (Cytokines) and 55% increased phagocytic activity by macrophages. The result indicates 3x (triple) immunity action of the Dabur ChyawanKidz Gummies, making it a unique choice of chewable immunomodulatory preparation, which appeals across ages, combining taste with immunity.

The effect of a diode-pumped solid-state laser with a wavelength of 589 nm on T-lymphocyte proliferation.

To assess how low-level laser irradiation affects T cells. The case-control interventional study was conducted from November 2021 to April 2022 after approval by the ethics review committee of the College of Medicine, Mustansiriyah University, Baghdad, Iraq, and comprised healthy individuals. Phlebotomy was used to collect 4ml of blood. A portion of each sample was exposed to 589nm laser radiation, while the other portion was used as a control. The irradiated sample was divided into whole blood and in-plate subgroups. Phytohemagglutinin was used for mitotic stimulation of T-lymphocytes, and cell proliferation assay was used to stimulate T lymphocytes measured using MTS assay (3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium). Optical density was measured using enzyme-linked immunosorbent assay. Data was analysed using GraphPad prism software. There were 35 subjects, 17(49%) males and 18 (51%) females, with an age range between 19-25 years, all without any disease or medication. Laser irradiation stimulated T-lymphocyte proliferation to levels that depended on the dose of laser used. At energy 30J/cm2 there was a significant increase in the in-plate subgroup of irradiated samples compared to controls and between the two irradiated subgroups (p<0.05). At 50J/cm2 dose, there was a significant increase in the whole blood subgroup compared to the controls (p<0.05). At 70J/cm2 dose, there was a significant difference in the whole blood subgroup compared to the controls, and between the two irradiated subgroups (p<0.05). The stimulation of T lymphocyte proliferation by the application of a 589nm laser could have medical applications in the field of immune system enhancement.

Variant-specific neutralising antibodies levels induced by the PHH-1 V SARS-CoV-2 vaccine (Bimervax®) by HIPRA

SARS-CoV-2 virus variants continue to emerge at an alarming rate due to spontaneous genetic mutations, particularly in the spike protein receptor-binding domain (RBD) portion, which render the virus more likely to escape immunity. So far, the immunity obtained through global primary and/or booster immunisation campaigns has been sufficient to protect the population from new emerging variants of the Omicron lineage. The current approach to update vaccines' antigen composition to new variants to boost immunity may not be sustainable in the long term. It might also be potentially redundant if the mutations are giving rise to variants which induce milder infections and existing vaccines, such as Bimervax®, are still sufficiently protective, as Covid is slowly becoming a seasonal illness. Through measuring neutralising antibody titres in sera from subjects boosted with Bimervax®, we have demonstrated the ability of Bimervax® to induce immune responses against a variety of SARS-CoV-2 variants, ranging from earlier variants inducing more serious infections to more recent variants which have been found to produce milder infections.

Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans.

Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination. We hypothesized that PEG-specific antibodies could increase the clearance of mRNA vaccines. To test this, we developed methods to quantify both the vaccine mRNA and ionizable lipid in frequent serial blood samples from 19 subjects receiving Moderna SPIKEVAX mRNA booster immunization. Both the vaccine mRNA and ionizable lipid peaked in blood 1-2 days post vaccination (median peak level 0.19 and 3.22 ng mL-1, respectively). The vaccine mRNA was detectable and quantifiable up to 14-15 days postvaccination in 37% of subjects. We measured the proportion of vaccine mRNA that was relatively intact in blood over time and found that the decay kinetics of the intact mRNA and ionizable lipid were identical, suggesting the intact lipid nanoparticle recirculates in blood. However, the decay rates of mRNA and ionizable lipids did not correlate with baseline levels of PEG-specific antibodies. Interestingly, the magnitude of mRNA and ionizable lipid detected in blood did correlate with the boost in the level of PEG antibodies. Furthermore, the ability of a subject's monocytes to phagocytose lipid nanoparticles was inversely related to the rise in PEG antibodies. This suggests that the circulation of mRNA lipid nanoparticles into the blood and their clearance by phagocytes influence the PEG immunogenicity of the mRNA vaccines. Overall, this work defines the pharmacokinetics of lipid nanoparticle mRNA vaccine components in human blood after intramuscular injection and the factors that influence these processes. These insights should be valuable in improving the future safety and efficacy of lipid nanoparticle mRNA vaccines and therapeutics.

Cost effectiveness analysis comparing varying booster intervals of vaccination policies to address COVID-19 situation in Thailand, 2023.

The COVID-19 booster immunization policy is cost-effective, but evidence on additional booster doses and appropriate strategies is scarce. This research compared the cost-effectiveness of annual, twice-a-year, and biennial booster dose policies. We performed stochastic modeling using compartmental susceptible-exposed-infectious-recovered models and a system dynamic model. We evaluated four policy scenarios: (1) hypothetical no-booster immunization policy; (2) twice-a-year vaccination policy; (3) annual vaccination policy; and (4) biennial vaccination policy. In addition, we conducted a one-way sensitivity analysis by adjusting R0 from 1.8 to 3.0 in all scenarios (epidemic stage) and by decreasing the vaccination cost by 50% at the end of the first year to reflect the current policy direction to enhance domestic vaccine production. Compared to non-booster policies, all three booster strategies reduced the number of cases, hospital admissions, and severe infections remarkably. Without a booster, total cases would reach 16,220,615 (95% confidence interval [CI] 6,726,550-29,661,112) by day 1,460, whereas, with a twice-a-year booster, the total cases would reach 597,901 (95% CI 526,230-694,458) in the same period. Even though the no booster scenario exhibited the lowest cost by approximately the first 500 days, by day 1,460 the biennial booster scenario demonstrated the lowest cost at 72.0 billion baht (95% CI 68.6-79.4 billion). The most cost-saving policy was the biennial booster scenario. The annual booster scenario also stood as a cost-effective option for most outcomes. In the epidemic stage and in an assumption where the vaccination costs dropped, all booster policies became more cost-effective or cost-saving compared with the main assumption. This study underscores the significance of the COVID-19 vaccine booster policy. Implementing policies should take into consideration cost-effectiveness, feasibility, and public communication.

Prime-boost immunization with inactivated human adenovirus type 55 combined with an adjuvant enhances neutralizing antibody responses in mice

BackgroundHuman adenovirus type 55 (hAd55) infection can lead to acute respiratory diseases that often present with severe symptoms. Despite its persistent prevalence in military camps and communities, there are no commercially available vaccines or vaccine candidates undergoing clinical evaluation; therefore, there is an urgent need to address this. In this study, we evaluated the immunogenicity of inactivated hAd55 isolates and investigated the effects of adjuvants and various immunization intervals.Methods and resultsTo select a vaccine candidate, four hAd55 strains (6–9, 6–15 (AFMRI 41014), 28–48 (AFMRI 41013), and 12–164 (AFMRI 41012)) were isolated from infected patients in military camps. Sequence analysis revealed no variation in the coding regions of structural proteins, including pentons, hexons, and fibers. Immunization with inactivated hAd55 isolates elicited robust hAd55-specific binding and neutralizing antibody responses in mice, with adjuvants, particularly alum hydroxide (AH), enhancing antibody titers. Co-immunization with AH also induced hAd14-specific neutralizing antibody responses but did not induce hAd11-specific neutralizing antibody responses. Notably, booster immunization administered at a four-week interval resulted in superior immune responses compared with shorter immunization intervals.ConclusionsPrime-boost immunization with the inactivated hAd55 isolate and an AH adjuvant shows promise as a potential approach for preventing hAd55-induced respiratory disease. Further research is needed to evaluate the efficacy and safety of these vaccine candidates in preventing hAd55-associated respiratory illnesses.

Antioxidant defence mechanism in hen egg: An immunity Booster

Dietary antioxidants are considered to be a vital agent that has the potential to reduce the risk of dangerous diseases by stabilizing redox homeostasis. Hen eggs are the most intrinsic part of our breakfast and a bang-up source of high-quality proteins, lipids, minerals and vitamins. Eggs show an antioxidant property due to the presence of proteins in both the yolk and white i.e. ovalbumin, Ovotransferrin and phosvitin. It’s also a fact that antioxidants in the eggs can be enhanced artificially by manipulating the poultry feed given to the hens. Lack of antioxidants and nutrients leads to a number of diseases including cancer, cardiovascular diseases and age-related macular degeneration.