Humoral Research Articles

Safety and immunogenicity of Ad26.COV2.S in adults: A randomised, double-blind, placebo-controlled Phase 2a dose-finding study

BackgroundA single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored. MethodsThis randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18–55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 1010, 2.5 × 1010, 5 × 1010, and 1 × 1011 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 1010 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants. ResultsAll Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 1010 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related. ConclusionThe study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 1010 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination.

A pupillary contrast response in mice and humans: Neural mechanisms and visual functions

A pupillary contrast response in mice and humans: Neural mechanisms and visual functions

Assessment of humoral and cellular immunity to SARS-COV-2 in end-stage renal disease patients treated with haemodialysis

Assessment of humoral and cellular immunity to SARS-COV-2 in end-stage renal disease patients treated with haemodialysis

Study on personal comfort heating system and human thermal comfort in extremely low-temperature building environments

Exposure to extremely low-temperature building environments around -20 °C causes various hazards to human health. However, few studies have studied human thermal comfort and physiological response in such environments, nor the personal comfort heating system. Thus, this study investigated the heating characteristics of personal comfort heating system, their effects on thermal responses, and thermophysiological parameters in extremely low-temperature building environments. We conducted experimental tests and questionnaires in a cryogenic enthalpy difference laboratory with air temperature ranging from -21.2 to -15.6 °C and a relative humidity of 55 %. Eight experimental conditions were designed with several heating measures (heating mat, heating gloves, heating cushion and airwarmer). The heating parameters of the personal comfort heating systems as well as the subjective evaluations and skin temperature of the subjects were recorded and analyzed. The results showed that the airwarmer confinement box condition had a corrective power of up to 38.3 K. The overall thermal sensation vote and overall thermal comfort vote were maintained at 0.25 and -0.25. Further, we found that the face, hands, calves and feet got cold easier with the largest skin temperature difference of -4.9, -8.1, -6.7 and -7.6 °C, respectively. Besides, the relationships between thermal responses and between thermal responses and skin temperature were examined, as well as a thermal comfort assessment methodology was established for extremely low-temperature environments.

Pediatric immunotherapy and HIV control

Purpose of review Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies. Recent findings During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials. Summary Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.

Mechanisms of antibody mediated immunity – Distinct in early life

Immune responses in early life are characterized by a failure to robustly generate long-lasting protective responses against many common pathogens or upon vaccination. This is associated with a reduced ability to generate T-cell dependent high affinity antibodies. This review highlights the differences in T-cell dependent antibody responses observed between infants and adults, in particular focussing on the alterations in immune cell function that lead to reduced T follicular helper cell-B cell crosstalk within germinal centres in early life. Understanding the distinct functional characteristics of early life humoral immunity, and how these are regulated, will be critical in guiding age-appropriate immunological interventions in the very young.

Anti_spike and anti_nucleocapsid IgG responses to SARS-CoV-2 in children of Jordan

BackgroundIt is proven that children have significantly milder COVID-19 disease compared to adults. Various immunological characteristics influence this age-related difference in protection against COVID-19. Pediatric COVID-19 in Jordan is extremely under reported. ObjectivesThe primary goal of this work is to identify the anti_S and anti_N antibody responses in a random group of children in Jordan and compare it to that of naturally infected-unvaccinated adults. Methods151 unvaccinated children, 4 days to 18 years old, were screened for anti_S and anti_N antibodies. History of COVID-19 infection or exposure to infection and symptom severity were reported by parents on a special questionnaire. Results78.9 % and 65.3 % of participants were seropositive for anti_S IgG and anti_N Abs, respectively. There was a remarkable association between age and anti_S IgG and anti_N IgG antibody titers, as children aged 12 years or older had increased anti_S IgG titers (mean = 19.3 BAU/mL) compared to younger groups (means of 10.15, 9.24, 7.91 BAU/mL for age groups 6–12, 1–6, less than 1 year, respectively). Gender did not show a statistically important role in anti_S and anti_N IgG seropositivity rates or titers. Children displayed significantly elevated anti_S titers (mean = 13.23 BAU/mL) compared to naturally infected adults (mean = 9.72 BAU/mL), in contrast, adults’ anti_N titers (mean = 39.64 U/mL) were significantly higher compared to those of children (mean = 10.77 U/mL). ConclusionsThe current work provides evidence of distinctly robust and persistent humoral immunity displayed by high anti_S and anti_N IgG in children, even >12 months post-infection. Age was the only factor that had a significant statistical impact on anti_S and anti_N Ab levels among the pediatric group in this study. Children exhibited significantly higher anti_S titers than naturally infected adults. In contrast, adults’ anti_N titers were significantly higher. Such information can assist direct pediatric SARS-CoV-2 immunization programs, with implications for creating age-targeted strategies for diagnostic and population protection measures.

Immunity by AS03ation: The natural adjuvantage

Humans do not respond equally to vaccination. To investigate why, Mulè etal. developed a multimodal framework and found that high responders after unadjuvanted influenza vaccination exist in a naturally adjuvanted state, mimicking innate immunophenotypes following AS03-adjuvanted vaccination. This highlights biological factors that set apart high-antibody responders and how adjuvants can boost innate immune cues to improve humoral immunity.

Functional role of TrIL-1β in Takifugu rubripes defense against Cryptocaryon irritans infection

The Japanese puffer, Takifugu rubripes, is a commercially important fish species in China that is under serious threat from white spot disease (cyptocaryoniasis), which leads to heavy economic losses. We previously found that interleukin-1β (IL-1β), an important cytokine with a potential role in resistance against pathogens, was one of the most significantly differentially up-regulated proteins in the gills and spleen of T. rubripes infected by the protozoan parasite Cryptocaryon irritans. In this study, we assessed the potential function of T. rubripes IL-1β (TrIL-1β) in fish infected with C. irritans. Phylogenetic analysis indicated that the TrIL-1β protein sequence was most closely related to that of Atlantic salmon (Salmo salar) (67.2 %). The incubation experiments revealed that TrIL-1β may reduce trophont activity by destroying membranes. Immunofluorescence experiments showed that recombinant TrIL-1β promoted the expression of endogenous IL-1β, which penetrated and disrupted the cell membranes of trophonts. Transmission electron microscopy showed that the IL-1β group had less tissue damage compared with control groups of fish. IL-1β-small interfering RNA and IL-1β overexpression experiments were performed in head kidney primary cells, and challenge experiments were performed in vitro. Quantitative RT-PCR results showed that TrIL-1β regulated and activated MyD88/NF-κB and MyD88/MAPK/p38 signaling pathways during C. irritans infection. TrIL-1β also promoted the differential expression of IgM, showing that it was involved in humoral immunity of T. rubripes. The cumulative mortality experiment show that TrIL-1β could protect fish against C. irritans infection. These results enrich current knowledge about the molecular structure of TrIL-1β. They also suggested that recombinant TrIL-1β could be used as an adjuvant in a subunit vaccine against C. irritans infection, which is of profound importance for the prevention and control of parasitic diseases in T. rubripes.

COVID 19: Cellular and humoral responses post-vaccination

COVID 19: Cellular and humoral responses post-vaccination

Between conflict and reciprocal habituation: Human-wild boar coexistence in urban areas

Urbanization is an ongoing global environmental change. Wildlife may respond using anthropized environments and resources, which is known as synurbization, creating human-wildlife interactions. Wild boar (Sus scrofa) populations have become common in urban areas, including the metropolitan area of Barcelona. Humans respond to wild boars in urban environments either habituating, with lower conflict perception and higher wild boar acceptance, or sensitizing, with reduced tolerance towards wild boars. Since citizen response influences conflict management, this study analysed the drivers of human responses, which should allow adopting socially-accepted measures to manage synurbic wild boar populations. Interviews to 1956 Barcelona citizens were performed, grouping the response variables to score citizen and urban characteristics, as well as citizen lay-knowledge, emotions, experiences, and perception of wild boar. Five citizen clusters were identified: cluster 1 (3.3 %), highly habituated and active wild boar feeder; cluster 2 (11.3 %), habituated to wild boars with positive feelings; cluster 3 (19.8 %), not habituated nor sensitized, willing to maintain urban wild boar populations; cluster 4 (29.1 %), sensitized and concerned, defending to reduce wild boar; and cluster 5 (40.1 %), highly sensitized and proposing to reduce or even eliminate wild boar. Positive attitudes associated wild boar to aesthetic value, closeness to nature and sympathy, and were more frequent in young citizens with urban background and high education, animal lovers habituated to wild boar through contact without negative experiences. Conversely, negative attitudes were concerned about city fouling, safety or health, accepted lethal management measures, and were more frequent in older citizens with rural background, lower education, low contact with wild boar or sensitized through negative experiences. We document for the first time the sensitization and reciprocal habituation of humans to wild boar in urban areas. The identification of the drivers of citizen attitudes towards urban wildlife should be useful to design socially-accepted management measures.

A DETAILED STUDY ON OCCUPATIONAL STRESS AMONG EMPLOYEES WITH REFERENCE TO TROJAN HUNT INDIA LLP

Stress can be defined as a state of worry or mental tension caused by a difficult situation. Stress is a natural human response that prompts us to address challenges and threats in our lives. Everyone experiences stress to some degree. The way we respond to stress, however, makes a big difference to our overall well-being. Job Stress and Health: - Stress sets off an alarm in the brain, which responds by preparing the body for defensive action. The nervous system is aroused and hormones are released to sharpen the senses, quicken the pulse, deepen respiration, and tense the muscles. This response (sometimes called the fight or flight response) is important because it helps us defend against threatening situations. The response is preprogrammed biologically. Everyone responds in much the same way, regardless of whether the stressful situation is at work or home. Short-lived or infrequent episodes of stress pose little risk. But when stressful situations go unresolved, the body is kept in a constant state of activation, which increases the rate of wear and tear to biological systems. Ultimately, fatigue or damage results, and the ability of the body to repair and defend itself can become seriously compromised. As a result, the risk of injury or disease escalates.

Is aromatic plants environmental health engineering (APEHE) a leverage point of the earth system?

It is important to note that every ecological niche in an ecosystem is significant. This study aims to assess the importance of medicinal and aromatic plants (MAPs) in the ecosystem from multiple perspectives. A primary model of Aromatic Plants Environmental Health Engineering (APEHE) has been designed and constructed. The APEHE system was used to collect aerosol compounds, and it was experimentally verified that these compounds have the potential to impact human health by binding to AKT1 as the primary target, and MMP9 and TLR4 as secondary targets. These compounds may indirectly affect human immunity by reversing drug resistance in drug-resistant bacteria in the nasal cavity. This is mainly achieved through combined mutations in sdhA, scrA, and PEP. Our findings are based on Network pharmacology and molecular binding, drug-resistance rescue experiments, as well as combined transcriptomics and metabolomics experiments. It is suggested that APEHE may have direct or indirect effects on human health.We demonstrate APEHE's numerous potential benefits, such as attenuation and elimination of airborne microorganisms in the environment, enhancing carbon and nitrogen storage in terrestrial ecosystems, promoting the formation of low-level clouds and strengthening the virtuous cycle of Earth's ecosystems. APEHE also supports the development of transdisciplinary technologies, including terpene energy production. It facilitates the creation of a sustainable circular economy and provides additional economic advantages through urban optimisation, as well as fresh insights into areas such as the habitability of other planets. APEHE has the potential to serve as a leverage point for the Earth system. We have created a new research direction.

SARS-CoV-2 cellular and humoral responses in vaccine-naive individuals during the first two waves of COVID-19 infections in the southern region of The Netherlands: a cross-sectional population-based study.

Data on adaptive cellular immunity are of interest to define immune protection against severe acute respiratory syndrome coronavirus 2 in a population, which is important for decision-making on booster-vaccination strategies. This study provides data on associations between participant characteristics and cellular immune responses in vaccine-naive individuals with different humoral responses.

Description Of The Usage Of Antiretroviral Medicine With Atc/Ddd Method In The Primary Health Care Centers Of Kediri 2021

AIDS (Acquired Immune Deficiency Syndrome) is a collection of symptoms and infections caused by damage to the human immune system, HIV (Human Immunodeficiency Virus ), a virus that can weaken human immunity. PLWHA patients must undergo antiretroviral virus (ARV) drug therapy, one of the drug use analysis classification systems is using the ATC/DDD system which is a means of researching drug use in an effort to improve the quality of drug use, one of these components is the presentation and comparison of drug consumption levels. international. The aim of this research is to determine the use of antiretroviral drug consumption in primary health care center in the Kediri City area for the 2021 period using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) method. The design of this research is quantitative descriptive, namely describing a particular event systematically and accurately and the treatment of this research is the process of collecting data and evaluating the use of antiretroviral drugs as well as verifying Primary health care center data by interviewing primary health care center pharmacists in the Kediri city area in 2021. Consumption of antiretroviral drugs (ARVs). ) is highest in the Campurejo primary health care center, namely Lamivudine (3TC) as much as 31.71%, Balowerti in primary health care center with Zidovudine (AZT) as much as 29.02% and Pesantren 1 primary health care center with the drug Nevirapine (NVP) as much as 32.62%, while the use of ARV drugs is low. At the Campurejo primary health care center, it was 0.0002% of the drug Dolutegravir (DTG), and at the Balowerti primary health care center, it was 0.0012% of the drug Dolutegravir (DTG), then at Pesantren 1 primary health care center , it was 0.0015% of the drug Dolutegravir (DTG). The incidence of HIV is still high in Indonesia, especially in the city of Kediri.

Precision Vaccine Development: Unraveling the Immunoinformatics Code Against Epstein-Barr Virus's T41 Glycoprotein 350/220

Epstein-Barr Virus (EBV) poses a substantial global health threat, with a 90% morbidity rate in adults worldwide. Linked to infectious mononucleosis, autoimmune diseases, and cancers, there is an imperative for effective preventive measures, given the absence of current vaccines or medications. This study employs a bioinformatics strategy to design an epitope vaccine targeting EBV. The primary target for immunity is the EBV glycoprotein 350/220 (gp350), which mediates attachment to B cells through complement receptor 2 (CR2/CD21). The selected protein, EBV glycoprotein 350/220 was chosen based on its role in pathogenicity. In the post-therapeutic approach, three-dimensional structure prediction, validation, and verification processes were conducted, followed by molecular docking studies to identify potential drug-binding sites and suitable therapeutic inhibitors for the target protein. The protein's ability to stimulate humoral and cell-mediated immunity was assessed, leading to the identification of a peptide segment ATNLFLLEL from positions 342 to 356 as the predominant T cell epitope. This epitope demonstrated compatibility with various HLA profiles, enhanced by its interaction with eight HLA-A and HLA-B alleles. Population coverage analysis revealed broad responsiveness across geographies, suggesting its potential as a widely applicable vaccine component. Its non-allergic classification further supports its potential efficacy for diverse individuals. Docking studies with HLA-B*3501 confirmed its significant affinity for MHC-I molecules, establishing it as a promising vaccination candidate. Additionally, a region from amino acid positions 253 to 310 was identified as containing potential B-cell epitopes, with the sequence "LGAGELALTMRSKKLP" showing promise due to its antigenic potential. This computational approach to epitope-based peptide vaccine design and target site prediction against EBV represents a pioneering advancement in EBV virus research, emphasizing the need for validation through <i>in vitro</i> and <i>in vivo</i> trials.

Evaluation of in vitro antioxidative and protective effects of kefir on cyclophosphamide-upon oxidative stress and lung damage in rats

Purpose: Kefir, a natural probiotic, has antioxidative and antitumor properties, as well as potential beneficial properties resulting from microbial species and fermentation. Cyclophosphamide (CYP) is a cytotoxic drug that is highly preferred in cancer therapy but can suppress both humoral and cellular immunity. The use of effective doses is limited because CYP has an immunosuppressive effect and causes multiple organ toxicity such as the lungs, and the use of effective high doses is restricted. Methods: Wistar albino rats were divided into 6 groups. As; control, 150 mg/kg CYP, 5 mg/kg kefir, 5 mg/kg kefir +150 CYP, l0 mg/kg kefir, l0 mg/kg kefir+150 CYP. Fermented kefirs from the 1st, 2nd and 3rd days were mixed and given to the rats for 12 days, while CYP was given as a single dose and ip on the 12th day of the experiment. The received parameters were evaluated. Results: It was observed that the OSI value, which indicates oxidative stress, increased in the CYP-administered group, and this level approached control in the CYP+kefir groups. In addition, while degeneration, intense inflammation in the interalveolar area, collapse of the alveoli, and intense inflammation around the bronchioles were observed in the lung parenchyma of CYP-administered rats, it was observed that these effects were effectively improved in the groups given kefir+CYP. Conclusion: In conclusion, in our study, it was observed that kefir showed antioxidative and protective effects on CYP-induced oxidative stress, congestion, alveolar damage and inflammation.

Use a smartphone app for predicting human thermal responses in hot environment

The object of this study is to predict of human thermophysiological state in hot environment to prevent heat stress or heat stroke. A key issue is the need to design effective tools for heat stroke risk assessment taking into account environmental conditions, physical activity, characteristics of human clothing and protective equipment. A mobile application has been developed, which, unlike existing analogs, provides users with data on the safe time of human under selected environmental conditions. The mobile application uses the method of mathematical modeling to predict important indicators of human thermophysiological state: body temperature, sweat evaporation, body water loss. The mathematical model takes into account the generation of metabolic heat, the transfer of heat inside the body, and the heat exchange of a human with the environment. This paper reports the results of using a mobile application for predicting human thermal responses under hot environmental conditions. With the help of the application, it was possible to determine the time of a human's safe stay depending on the intensity of his/her activity and the characteristics of his/her clothing. It is shown that walking at a speed of 6 km/h in a military uniform is safe for 1 hour at an air temperature of 36 °C. Running at a speed of 8 km/h under such conditions becomes risky already after 15 minutes due to overheating of the human body. The developed information technology is designed to warn about heat stress or heat stroke of people who are under hot conditions in order to preserve their health and work capacity. The received predicting data should be considered as one of the theoretical measures to prevent human heat stress under hot environmental conditions

Chirped flicker optoretinography for in vivo characterization of human photoreceptors' frequency response to light.

Flicker electroretinography (ERG) has served as a valuable noninvasive objective tool for investigating retinal physiological function through the measurement of electrical signals originating from retinal neurons in response to temporally modulated light stimulation. Deficits in the response at certain frequencies can be used as effective biomarkers of cone-pathway dysfunction. In this Letter, we present the progress we made on its optical counterpart-photopic flicker optoretinography (f-ORG). Specifically, we focus on the measurement of the response of light-adapted retinal photoreceptors to a flicker stimulus with chirped frequency modulation. In contrast to measurements performed at discrete frequencies, this technique enables a significantly accelerated characterization of photoreceptor outer segment optical path length modulation amplitudes in the nanometer range as a function of stimulus frequency, enabling the acquisition of the characteristic frequency response in less than 2 sec.

Resistant starch from a tuberous root from the Andes cordillera improves metabolic and immune parameters in broilers

Resistant starch (RS) is a carbohydrate that exerts benefits on health. The present study aimed to research the effects of the Canna edulis Ker RS on metabolic and immune system indicators in broiler chickens. A total of 360 1- day-old male chicks were allotted to dietary treatments with 0% (RS0), 1% (RS1), and 2% (RS2) of RS inclusion. Chickens of RS1 and RS2 presented a lower rate of increase in serum glucose between the third and fifth week, with 50.9, 21.4, and 26.8% to RS0, RS1, and RS2, respectively. The higher serum cholesterol HDL was observed in broilers that consumed RS1 and RS2 diets at the fifth week of age (p < 0.05). The butyric acid levels of 16.59, 64.95, and 76.77 μmol/g were found in caecal content to RS0, RS1, and RS2, respectively (p < 0.01). The serum IgA levels were increased in broilers fed with the RS1 diet and decreased with the RS0 diet. The IgM was increased linearly as a function of age in the broilers RS1 and RS2. The subpopulation of T helper lymphocytes CD3+ CD4+ were increased in broilers fed with RS2 diet. The RS level that optimizes the humoral response was established as 1.07% and 1.56% for IgA and IgM, respectively (p < 0.05). The dietary inclusion of RS from C. edulis stimulated homeostasis of glucose and cholesterol with increase of HDL and caecal SCFA. Consequently, RS from C. edulis can be used as a nutraceutical additive in the broilers' diet.