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SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population. [ABSTRACT FROM AUTHOR]

Abstract Background The recently developed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). Methods We retrospectively measured serum SARS‐CoV‐2 antibodies against the spike protein (S‐IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S‐IgG titers ≥300 antibody units/mL). Results Although active anti‐myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B‐cell maturation antigen‐targeted therapy. Dose 3 (booster vaccination) led to significantly higher S‐IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine‐induced cellular immune response in patients using T‐spot Discovery SARS‐CoV‐2 kit, revealed an enhanced cellular immune response after Dose 3. Conclusions This study highlighted the significance of booster SARS‐CoV‐2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine‐induced humoral immune response.

Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time. Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7–15 weeks and 2) 6–8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated. Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7–15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134–1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325–26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5–80), 51.5 (14.8–132), and 19.5 (8.8–54.2) units, respectively, for 6–8 months after dose two, 3 weeks, and 3 months after dose three. Conclusions: Our data show that a third dose of SARS‑CoV‑2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.

Background: The recently developed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). Methods: We retrospectively measured serum SARS‐CoV‐2 antibodies against the spike protein (S‐IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S‐IgG titers ≥300 antibody units/mL). Results: Although active anti‐myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B‐cell maturation antigen‐targeted therapy. Dose 3 (booster vaccination) led to significantly higher S‐IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine‐induced cellular immune response in patients using T‐spot Discovery SARS‐CoV‐2 kit, revealed an enhanced cellular immune response after Dose 3. Conclusions: This study highlighted the significance of booster SARS‐CoV‐2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine‐induced humoral immune response. [ABSTRACT FROM AUTHOR]

Relevance. Active mass vaccination of the population against a new COVID-19 is being carried out on the territory of the Russian Federation, which is recognized as a priority strategy for the country's healthcare for the near and long-term periods. One of the main risk groups that are subject to priority vaccination is medical workers. Aims. To evaluate the effectiveness of vaccination of medical organizations ' employees against COVID-19 based on the results of a 6-month prospective follow-up. Materials and methods. The observation group consisted of 356 employees of a medical organization who were vaccinated against COVID-19 with the drug «Gam-Covid-Vac» from December 2020 to April 2021. The effectiveness of vaccination of employees was evaluated by the coefficient of IgG positivity to SARS-CoV-2 by solid-phase enzyme immunoassay 3 weeks after the first administration and 3–4 weeks after the second administration of the vaccine and then 1 time per month. Employees who were revaccinated after 5–6 months. After the initial vaccination, they were examined 10–14 days after the introduction of the first component «Gam-Covid-Vac». A total of 1921 serum samples were studied. A specific T-cell immune response was determined in two study participants without seroprotection after administration of two components of the «Gam-Covid-Vac» vaccine and eight employees with the elimination of IgG antibodies 4–5 months after vaccination using ELISPOT technology. In addition, 92 blood serum samples of 32 employees from the observation group were examined for specific antibodies to adenovirus by indirect enzyme immunoassay. From December 2020 to June 2021, the study participants were subjected to dynamic clinical observation, once a week they were examined by PCR to detect SARS-CoV-2 RNA in smears from the pharynx and nose (a total of 5696 samples). Results. After the completed course of immunization, the formation of both a humoral (in 99.4% of cases) and cellular immune response (100% among the studied samples) was confirmed. In the next 6 months after vaccination, cases of coronavirus infection were registered in 4.8% of those vaccinated, including 1 person – in the first month after vaccination and 16 – 3–5 months after vaccination. In all cases, the disease occurred in the form of an acute respiratory infection of mild or moderate severity and was characterized by a shorter period of virus isolation compared to similar data on the persistence of the virus in unvaccinated patients (15 days in vaccinated compared to 22 days in unvaccinated). It was found that the presence of immunity to adenovirus infection during vaccination with the drug «Gam-Covid-Vac» did not affect the possibility of forming an immune response to COVID-19. In the group of persons re-vaccinated with the first component of «Gam-Covid-Vac» after 5–6 months. after the initial vaccination, an immune response was received during the follow-up period. Conclusion. Thus, according to the results of the study, a high immunological and epidemiological effectiveness of vaccination against COVID-19 with the drug «Gam-Covid-Vac» was established in a group of medical workers, and the effectiveness and safety of the administration of a booster dose of the vaccine after primary vaccination was also shown.

Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time. Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7-15 weeks and 2) 6-8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated. Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7-15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134-1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325-26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5-80), 51.5 (14.8-132), and 19.5 (8.8-54.2) units, respectively, for 6-8 months after dose two, 3 weeks, and 3 months after dose three. Conclusions: Our data show that a third dose of SARS-CoV-2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals. [ABSTRACT FROM AUTHOR]

Self-amplifying replicon RNA (RepRNA) promotes expansion of mRNA templates encoding genes of interest through their replicative nature, thus providing increased antigen payloads. RepRNA derived from the non-cytopathogenic classical swine fever virus (CSFV) targets monocytes and dendritic cells (DCs), potentially promoting prolonged antigen expression in the DCs, contrasting with cytopathogenic RepRNA. We engineered pestivirus RepRNA constructs encoding influenza virus H5N1 (A/chicken/Yamaguchi/7/2004) nucleoprotein (Rep-NP) or hemagglutinin (Rep-HA). The inherent RNase-sensitivity of RepRNA had to be circumvented to ensure efficient delivery to DCs for intracellular release and RepRNA translation; we have reported how only particular synthetic delivery vehicle formulations are appropriate. The question remained concerning RepRNA packaged in virus replicon particles (VRPs); we have now compared an efficient polyethylenimine (PEI)-based formulation (polyplex) with VRP-delivery as well as naked RepRNA co-administered with the potent bis-(3’,5’)-cyclic dimeric adenosine monophosphate (c-di-AMP) adjuvant. All formulations contained a Rep-HA/Rep-NP mix, to assess the breadth of both humoral and cell-mediated defences against the influenza virus antigens. Assessment employed pigs for their close immunological relationship to humans, and as natural hosts for influenza virus. Animals receiving the VRPs, as well as PEI-delivered RepRNA, displayed strong humoral and cellular responses against both HA and NP, but with VRPs proving to be more efficacious. In contrast, naked RepRNA plus c-di-AMP could induce only low-level immune responses, in one out of five pigs. In conclusion, RepRNA encoding different influenza virus antigens are efficacious for inducing both humoral and cellular immune defences in pigs. Comparisons showed that packaging within VRP remains the most efficacious for delivery leading to induction of immune defences; however, this technology necessitates employment of expensive complementing cell cultures, and VRPs do not target human cells. Therefore, choosing the appropriate synthetic delivery vehicle still offers potential for rapid vaccine design, particularly in the context of the current coronavirus pandemic.

Self-amplifying replicon RNA (RepRNA) promotes expansion of mRNA templates encoding genes of interest through their replicative nature, thus providing increased antigen payloads. RepRNA derived from the non-cytopathogenic classical swine fever virus (CSFV) targets monocytes and dendritic cells (DCs), potentially promoting prolonged antigen expression in the DCs, contrasting with cytopathogenic RepRNA. We engineered pestivirus RepRNA constructs encoding influenza virus H5N1 (A/chicken/Yamaguchi/7/2004) nucleoprotein (Rep-NP) or hemagglutinin (Rep-HA). The inherent RNase-sensitivity of RepRNA had to be circumvented to ensure efficient delivery to DCs for intracellular release and RepRNA translation; we have reported how only particular synthetic delivery vehicle formulations are appropriate. The question remained concerning RepRNA packaged in virus replicon particles (VRPs); we have now compared an efficient polyethylenimine (PEI)-based formulation (polyplex) with VRP-delivery as well as naked RepRNA co-administered with the potent bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) adjuvant. All formulations contained a Rep-HA/Rep-NP mix, to assess the breadth of both humoral and cell-mediated defences against the influenza virus antigens. Assessment employed pigs for their close immunological relationship to humans, and as natural hosts for influenza virus. Animals receiving the VRPs, as well as PEI-delivered RepRNA, displayed strong humoral and cellular responses against both HA and NP, but with VRPs proving to be more efficacious. In contrast, naked RepRNA plus c-di-AMP could induce only low-level immune responses, in one out of five pigs. In conclusion, RepRNA encoding different influenza virus antigens are efficacious for inducing both humoral and cellular immune defences in pigs. Comparisons showed that packaging within VRP remains the most efficacious for delivery leading to induction of immune defences; however, this technology necessitates employment of expensive complementing cell cultures, and VRPs do not target human cells. Therefore, choosing the appropriate synthetic delivery vehicle still offers potential for rapid vaccine design, particularly in the context of the current coronavirus pandemic. [ABSTRACT FROM AUTHOR]

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections.

Understanding the relationship between patient immune characteristics, disease severity, and mortality represents a critical step in the fight against COVID-19. Elevated levels of programmed death ligand-1 (PD-L1) and Neutrophil-lymphocyte ratio (NLR) are linked to increased severity of acute COVID-19 in patients. This study aimed to investigate the association of the combination of sPD-L1 and NLR with 1-year Mortality in patients with COVID-19. A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of sPD-L1 in the blood serum was evaluated by ELISA. The effect of biomarkers on the development of mortality was analyzed with multivariate regression. The risk of mortality within one year HR was 2.46 if the plasma sPD-L1 value of more than 277.13 pg/ml, and for NLR more than 2.46 HR was 2.87. The model of combining sPD-L1 and NLR resulted in an improvement in the predictive accuracy of the Hazard Ratio 7.6 (95 % CI: 3.02–19.11). The combination of two immune-mediated markers (sPD-L1 and NLR), which reflect the systemic inflammatory balance of activation and exhaustion, can complement each other and improve the assessment of the risk of death in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab. Nivolumab targets the immune-check point inhibitor programmed cell death-1 and was used for squamous non-small cell lung cancer. Partly reversible neurologic and psychiatric symptoms and unremarkable brain magnetic resonance imaging (MRI) were observed after the first course. Neurological symptoms progressed and recurrent seizures developed after the second course. Brain MRI disclosed multiple edematous and confluent supra- and infratentorial lesions, partly with contrast-enhancement. We excluded autoimmune and paraneoplastic causes and performed ancillary investigations to rule out common and opportunistic infections. Eventually, postmortem histopathological analysis of the brain revealed a necrotizing process, which contrasts previous cases reporting parenchymal immune cell infiltration or demyelination. Appropriate diagnostic pathways and treatment algorithms need to be implemented for the work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment.

Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immunerelated adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab. Nivolumab targets the immune-check point inhibitor programmed cell death-1 and was used for squamous non-small cell lung cancer. Partly reversible neurologic and psychiatric symptoms and unremarkable brain magnetic resonance imaging (MRI) were observed after the first course. Neurological symptoms progressed and recurrent seizures developed after the second course. Brain MRI disclosed multiple edematous and confluent supra- and infratentorial lesions, partly with contrast-enhancement. We excluded autoimmune and paraneoplastic causes and performed ancillary investigations to rule out common and opportunistic infections. Eventually, postmortem histopathological analysis of the brain revealed a necrotizing process, which contrasts previous cases reporting parenchymal immune cell infiltration or demyelination. Appropriate diagnostic pathways and treatment algorithms need to be implemented for the work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment. [ABSTRACT FROM AUTHOR]

Malaria remains as a global life-threatening disorder due to the emergence of resistance against standard antimalarials. Consequently, there is a serious need to better understand the biology of the malaria parasite in order to determine appropriate targets for new interventions. Calcyclin binding protein (CacyBP) is a multi-functional and multi-ligand protein that is not well characterized in malaria disease. In this study, we have cloned CacyBP from rodent species Plasmodium yoelii nigeriensis and purified the recombinant protein to carry out its detailed molecular, biophysical and immunological characterization. Molecular characterization indicates that Py CacyBP is a ∼27 kDa protein in parasite lysate and exists in monomer and dimer forms. Bioinformatic analysis of CacyBP showed significant sequence and structural similarities between rodent and human malaria parasites. CacyBP is expressed in all blood stages of P. yoelii nigeriensis parasite. In silico studies proposed the immunogenic potential of CacyBP. The r Py CacyBP immunized mice exhibited elevated levels of IgG1, IgG2a, IgG2b and IgG3 in their serum. Notably, cellular immune response in splenocytes from immunized mice showed increased expression of pro-inflammatory cytokines such as IL-12, IFN-γ and TNF-α. This CacyBP exhibited pro-inflammatory immune response in rodent host. These finding revealed that CacyBP may have the potential to boost the host immunity for protection against malaria infection. The present study provides basis for further exploration of the biological function of CacyBP in malaria parasite. [Display omitted] • Calcyclin binding protein (CacyBP), ∼27 kDa in size, is present in rodent malaria parasite. • Bioinformatic study reflects that CacyBP is multi-domain protein which might be involved in many cellular processes. • Recombinant CacyBP protein is present in both monomer (∼30 kDa) and dimer (∼60 kDa) form in malaria parasites. • CacyBP is expressed in all blood stages of the parasite. • CacyBP elicited both humoral and cellular immune response in rodent host. [ABSTRACT FROM AUTHOR]

Background Infection with different species of cutaneous human papillomaviruses (cHPV) of genus alpha (cαHPVs) and associated skin disease are highly prevalent in solid organ transplant recipients (OTR), documenting the importance of the immunological control of HPV infection. Objectives To investigate the natural course of cαHPV-specific cellular and humoral immune responses during systemic long-term immunosuppression. Methods Integrating bead-based multiplex serology and flow cytometry we analyzed natural cαHPV-specific antibodies and T H cell responses against the major capsid protein L1 of HPV types 2, 27, 57 (species 4) and 3, 10 and 77 (species 2) in sera and blood of OTR before and after initiation of iatrogenic immunosuppression and in comparison to immunocompetent individuals (IC). Results Among OTR we observed an overall 42% decrease in humoral L1-specific immune responses during the course of iatrogenic immunosuppression, comparing median values 30d before and 30d after initiation of immunosuppressive therapy ( p < 0.05). This difference disappeared after long-term (>1 year) immunosuppression. The predominant cellular L1-specific immune response was of type T H 1 (CD4 + CD40L + IL-2 + IFN-γ + ). Consistent with the detected L1-specific antibody titers, L1-specific T H 1 responses were unchanged in long-term immunosuppressed OTR compared to IC. Notably, cαHPV-L1-specific IL-2 + /CD40L + CD4 + or IFN-γ + /CD40L + CD4 + T H cell responses against any of the cαHPV-L1 types were significantly higher in OTR with clinically apparent common warts. Conclusion The systemic humoral immune response against cαHPV may reflect the individual degree of iatrogenic immunosuppression indicating a higher susceptibility for cαHPV infection among OTR during the early phase after organ transplantation. Humoral cαHPV-specific immune responses may show a reconstitution to pre-transplantation levels despite continuous potent immunosuppression. [ABSTRACT FROM AUTHOR]

A wide variety of dietary supplements containing polysaccharides are being introduced on the market. One of them is Leiber Beta-S (β-1,3/1,6-D-glucan) whose immunostimulatory effects have not yet been fully evaluated, in particular in polygastric animals. The aim of this study was to evaluate the effect of this supplement on selected indicators of cellular and humoral immunity in calves. The experiment was performed on 14 calves aged 30 ± 2 days, divided into two equal groups of control and experimental animals. The feed administered to calves of the experimental group was supplemented with Leiber Beta-S at 50 mg/kg body weight, whereas control calves were administered standard farm-made feed without supplementation. Blood was sampled before the experiment (day 0) and on days 15, 30 and 60 to determine the immunity indicators (proliferative response of lipopolysaccharide- and concanavalin A-stimulated lymphocytes, respiratory burst activity, potential killing activity of phagocytes, gamma globulin concentrations, lysozyme activity, ceruloplasmin activity) and biochemical indicator (total protein concentrations). Diet supplemented with Leiber Beta-S stimulated the immune system of calves. Significant differences between the experimental and the control group were found in lysozyme and ceruloplasmin activity, gamma globulin concentrations, potential killing activity of phagocytes, proliferative response of lymphocytes (P < 0.001) and respiratory burst activity of phagocytes (P < 0.05). No differences were found in the serum total protein between the experimental and the control group. This study reports for the first time the effect of Leiber Beta-S (β-1,3/1,6-D-glucan) on selected biochemical and immunity indicators in calves. [ABSTRACT FROM AUTHOR]

The most neglected aspects of Chagas disease (CD) have been patient care and treatment. Despite recent progress in the development of potentially improved drugs, there is no consensus among different research groups on the lack of therapeutic response markers to evaluate efficacy of newly proposed drugs early after treatment. A systematic review of current evidence regarding molecules which are potential biomarkers for therapeutic response has been conducted using quality assessment and target responses as primary criteria. The review provides a panorama of the cumulative evidence and specific needs for development of a battery of complementary biomarkers which together fulfill ideal or acceptable criteria to evaluate early responses to treatment for chronic CD. There are several marker candidates which together may fulfill acceptable criteria to indicate the efficacy of a trypanocidal treatment. Data from ongoing studies are considered essential to improve assessment of existing markers and to identify those for early follow-up of treated patients. [ABSTRACT FROM AUTHOR]

Abstract: Hormones are an important interface between genome and environment, because of their ability to modulate the animal’s phenotype. In particular, corticosterone, the stress hormone in lizards, is known to reallocate energy from non-essential functions to affect morphological, physiological and behavioral traits that help the organism to deal with acute or chronic stressors. However, the effects of corticosterone on life history stages are still unclear primarily because of the dependence of life history stages on both internal and external factors. Using a cross-design, we tested the effect of elevated levels of exogenous corticosterone on the physiology of pregnant females in different immune contexts in a wild population of common lizards (Lacerta vivipara). Immune challenge was induced by the injection of sheep red blood cells (SRBC) and corticosterone levels were increased using a transdermal administration of corticosterone. Thereafter, reproductive traits, metabolism and cellular immune responses were measured. The elevation of corticosterone in pregnant females significantly altered reproductive and physiological performance. The corticosterone treatment decreased clutch success, juvenile size and body condition, but enhanced measures of physiological performance, such as metabolism and catalase activity. These first results reinforce the understanding of the physiological actions of corticosterone in reptiles. The data also demonstrated different direct impacts of immune challenge by SRBC on inflammatory response and antioxidant activity. The injection of SRBC stimulated the SOD activity in larger females. Finally, we demonstrated experimentally the modulation of the corticosterone action by the immune challenge on stamina and hatching date. [ABSTRACT FROM AUTHOR]

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections. [ABSTRACT FROM AUTHOR]

Abstract: Tryptophan-rich protein from P. yoelii called PypAg3 had shown protection in a murine model. We describe here its P. vivax orthologue named PvTRAg39.8 which is expressed during schizont stages of the parasite. The transcription initiation site was mapped to the −41 nucleotide position from the first AUG codon and thus established the ORF of PvTRAg39.8 which codes for a 322aa long protein. The sequence of this protein is highly conserved among the P. vivax isolates. Recombinant PvTRAg39.8 was expressed in E. coli, purified to electrophoretic homogeneity, and used for immunological studies. A majority of P. vivax-exposed individuals (90%, n =50) contained antibodies against the recombinant PvTRAg39.8. There was a switching of immunoglobulin isotypes against this antigen from IgG1 to IgG4 among individuals from the acute phase of P. vivax infection to convalescence. The PBMCs of 80% of the total 20 P. vivax-exposed individuals showed proliferation when stimulated with this antigen. The cytokine pattern produced by the PBMCs of the P. vivax-exposed individuals, after stimulation with this antigen, indicated a mixed type of immune response with a distinct bias towards the Th2 anti-inflammatory profile. Because of its high natural immunogenicity, conserved nature, and the protective properties of its P. yoelii counterpart, this protein may be a potential candidate for developing the immunotherapeutic reagents. [Copyright &y& Elsevier]

Summary: Despite the immense global efforts, the malaria vaccine is not yet available and requires the identification of newer target molecules. Since tryptophan-rich proteins of P. yoelii have been proposed as vaccine candidates, we describe here the expression, purification and immunological characterization of a 55kDa Plasmodium vivax tryptophan- and alanine-rich antigen (PvTARAg55). This protein consists of 480 aa residues with a calculated molecular mass of 55.0kDa. It shows 42% aa sequence identity (64% homology) with PyPAg1 of P. yoelii and shares positional conservation of tryptophan residues. Sequence analysis of PvTARAg55 from different P. vivax isolates revealed that typtophan-rich domain which contains most of the B-cell epitopes was highly conserved in the parasite population while the alanine-rich domain showed polymorphism. Exon-2 covering major part (420 aa) of the protein including both the domains was PCR amplified, cloned, expressed in Escherichia coli, and the recombinant protein purified to its homogeneity. Majority of P. vivax-infected individuals (82.5%, n =40) produced antibodies against this antigen. Proliferative responses to the recombinant PvTARAg55 were observed in 60% (n =20) of individuals who had recently been exposed to the P. vivax infection. Measurement of Th1- (IFN-γ, TNF-α, and IL-12) and Th2-type (IL-4 and IL-10) cytokine production in response to this recombinant antigen revealed a mixed type T-cell response with a Th2 response being more pronounced. These results demonstrate that PvTARAg55 elicits high humoral and cellular immune responses thus establishes its immunogenecity in humans. [Copyright &y& Elsevier]

Marchuk's model of a general immune reaction is presented in the paper. The results of investigation of the model are summarized. The qualitative behaviour of solutions to the model and its simplification is described. Many illustrations of recovery process, oscillations or lethal outcomes of a disease are shown. The model with time-dependent immune reactivity is also considered. Periodic dynamics caused by different reasons are compared. In the last section adaptation of the model to tumour-immune interactions is proposed. The role of interleukins in immune processes is taken into account to adapt Marchuk's model to tumour growth dynamics. Possible immunotherapy is also considered in the proposed model. Some preliminary analysis of the model is presented. [ABSTRACT FROM AUTHOR]

Background: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality., Methods: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273., Results: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% ( p  < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p  < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients., Conclusion: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols., Competing Interests: PA, NB, KB, IB, AB-N, SC, KE, RF-W, KF, FG, XG, CH, JH, CK, FK, AK, HK, TL, TL, HM, RM, FM, PM, AP, AP, FP, TP, HR, JS, HS, JS, HS, TS, JS, AS, TS, US, JS, TW, TT, LA, KA-R, MA have no conflict of interests. JB has a relationship with the German Ministry of Health via Hannover Medical School and receives study coordination and per-patient fees for Crit-CoV-U study (proteomic prediction of COVID-19 severity). The study has been supported by a grant from the Else-Kröner-Fresenius-Stiftung., (© 2021 The Authors.)