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• Long COVID links to an activated immune response, with increased M1 macrophages, T helper (Th) 1, Th17, and C-reactive protein. • Immune-related neurotoxicity and inflammatory pathways are key in the pathophysiology of Long COVID. Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there is no comprehensive meta -analysis focusing on activation of the immune inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS) along with other immune phenotypes in LC patients. This meta -analysis is designed to explore the IRS and CIRS profiles in LC patients, the individual cytokines, chemokines, growth factors, along with C-reactive protein (CRP) and immune-associated neurotoxicity. To gather relevant studies for our research, we conducted a thorough search using databases such as PubMed, Google Scholar, and SciFinder, covering all available literature up to July 5th, 2024. The current meta -analysis encompassed 103 studies that examined multiple immune profiles, C-reactive protein, and 58 cytokines/chemokines/growth factors in 5502 LC patients versus 5962 normal controls (NC). LC patients showed significant increases in IRS/CIRS ratio (standardized mean difference (SMD: 0.156, confidence interval (CI): 0.062;0.250), IRS (SMD: 0.338, CI: 0.236;0.440), M1 macrophage (SMD: 0.371, CI: 0.263;0.480), T helper (Th)1 (SMD: 0.316, CI: 0.185;0.446), Th17 (SMD: 0.439, CI: 0.302;0.577) and immune-associated neurotoxicity (SMD: 0.384, CI: 0.271;0.497). In addition, CRP and 21 different cytokines displayed significantly elevated levels in LC patients compared to NC. LC disease is characterized by IRS activation and increased immune-associated neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. Methods: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. Results: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. Conclusions: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant. [ABSTRACT FROM AUTHOR]

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Abstract Background The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. Methods Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. Results Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. Conclusions In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

ABSTRACTIntroduction Technological innovations have been instrumental in advancing vaccine design and protective benefit. Improvements in the safety, tolerability, and efficacy/effectiveness profiles have profoundly reduced vaccine-preventable global disease morbidity and mortality. Here we present an original vaccine platform, the Multiple Antigen Presenting System (MAPS), that relies on high-affinity interactions between a biotinylated polysaccharide (PS) and rhizavidin-fused pathogen-specific proteins. MAPS allows for flexible combinations of various PS and protein components.Areas covered This narrative review summarizes the underlying principles of MAPS and describes its applications for vaccine design against bacterial and viral pathogens in non-clinical and clinical settings.Expert opinion The utilization of high-affinity non-covalent biotin–rhizavidin interactions in MAPS allows for combining multiple PS and disease-specific protein antigens in a single vaccine. The modular design enables a simplified exchange of vaccine components. Published studies indicate that MAPS technology may support enhanced immunogenic breadth (covering more serotypes, inducing B- and T-cell responses) beyond that which may be elicited via PS- or protein-based conjugate vaccines. Importantly, a more detailed characterization of MAPS-based candidate vaccines is warranted, especially in clinical studies. It is anticipated that MAPS-based vaccines could be adapted and leveraged across numerous diseases of global public health importance.

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Abstract Background The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice. [ABSTRACT FROM AUTHOR]

Objectives: In the post‐SARS‐CoV‐2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti‐Spike (S) immunoglobulin‐G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T‐cell response assessment to enhance the definition of immune memory profile. Methods: SARS‐CoV‐2 interferon‐gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti‐receptor‐binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. Results: Close to 40% of our samples were exclusively IGRA‐positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long‐lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti‐receptor‐binding domain IgG and IGRA levels tended to reduce it. Conclusion: The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level. [ABSTRACT FROM AUTHOR]

Background: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: Among other limitations, the currently available vaccines against paratuberculosis do not offer complete protection against infection, and further vaccine development is limited by a lack of understanding of the mechanisms behind vaccine-induced protection. In this regard, the most recent studies have demonstrated that neutrophil function can be modulated through vaccination against several pathogens, including Mycobacterium avium subspecies paratuberculosis (Map). However, this modulation has not been described in ruminants, which are the natural hosts of Map. In the present work, the effect of vaccination on the neutrophil response against Map was assessed in goats using the only available vaccine against small ruminant paratuberculosis, Gudair®. No differences were found in the ex vivo response of neutrophils isolated from non-vaccinated and vaccinated animals, which suggests that the protection conferred by this heat-inactivated vaccine is based on mechanisms other than neutrophil modulation. It is possible that neutrophil modulation depends largely on the intensity of the immune response elicited by the vaccine employed or the antigen dose, as the previous reports which observed this modulation used live attenuated vaccines or were performed in laboratory animals using experimental vaccines. Neutrophils are believed to play a role in the initial stages of paratuberculosis, and it has recently been demonstrated that vaccination can modulate their function via priming or through epigenetic and metabolic reprogramming (training). Modulation of the neutrophil response against Mycobacterium avium subspecies paratuberculosis (Map) through vaccination has been demonstrated in a rabbit model but not in ruminants. Therefore, in the present work, the effect of vaccination on the response of caprine neutrophils against Map was studied. Neutrophils were isolated from non-vaccinated (n = 7) and Gudair®-vaccinated goat kids (n = 7), before vaccination and 30 days post-vaccination. Then, several neutrophil functions were quantified ex vivo: cell-free and anchored neutrophil extracellular trap (NET) release, phagocytosis, and the differential expression of several cytokines and TLR2. The induction of cell-free NETosis and TLR2 expression by Map is reported for the first time. However, vaccination showed no significant effect on any of the functions studied. This suggests that the protection conferred by Gudair® vaccination is based on mechanisms that are independent of the neutrophil function modulation. Further research into the impact of alternative vaccination strategies or the paratuberculosis infection stage on ruminant neutrophil function could provide valuable insights into its role in paratuberculosis. [ABSTRACT FROM AUTHOR]

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches. [ABSTRACT FROM AUTHOR]

Background: The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. Objective: This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Methods: Forty healthy volunteers (age: 35–60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Results: Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers’ cellular and humoral immune functions. Conclusion: In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

In the face of the ever-present burden of emerging and reemerging infectious diseases, there is a growing need to comprehensively assess individual- and population-level immunity to vaccine-preventable diseases (VPDs). Many of these efforts, however, focus exclusively on antibody-mediated immunity, ignoring the role of T cells. Aimed at clinicians, public health practioners, and others who play central roles in human vaccine research but do not have formal training in immunology, we review how vaccines against infectious diseases elicit T cell responses, what types of vaccines elicit T cell responses, and how T cell responses are measured. We then use examples to demonstrate six ways that T cells contribute to protection from VPD, including directly mediating protection, enabling antibody responses, reducing disease severity, increasing cross-reactivity, improving durability, and protecting special populations. We conclude with a discussion of challenges and solutions to more widespread consideration of T cell responses in clinical vaccinology.

The application of recombinant herpesvirus of turkey, expressing the H9 hemagglutinin gene from low pathogenic avian influenza virus (LPAIV) H9N2 and the avian orthoavulavirus-1 (AOAV-1) (commonly known as Newcastle Disease virus (NDV)) fusion protein (F) as an rHVT-H9-F vaccine, is an alternative to currently used classical vaccines. This study investigated H9- and ND-specific humoral and mucosal responses, H9-specific cell-mediated immunity, and protection conferred by the rHVT-H9-F vaccine in specific pathogen-free (SPF) chickens. Vaccination elicited systemic NDV F- and AIV H9-specific antibody response but also local antibodies in eye wash fluid and oropharyngeal swabs. The ex vivo H9-specific stimulation of splenic and pulmonary T cells in the vaccinated group demonstrated the ability of vaccination to induce systemic and local cellular responses. The clinical protection against a challenge using a LPAIV H9N2 strain of the G1 lineage isolated in Morocco in 2016 was associated with a shorter duration of shedding along with reduced viral genome load in the upper respiratory tract and reduced cloacal shedding compared to unvaccinated controls. [ABSTRACT FROM AUTHOR]

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)‐cells have recently gained much attention. We performed an in‐deep phenotypic analysis of NK‐cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty‐seven PLWH (22 long‐term EC [PLWH‐long‐term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH‐onART], and 10 noncontrollers cART‐naïve [PLWH‐offART]), and 20 uninfected controls were included. NK‐cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK‐cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK‐cells clusters based on the expression levels of the 15 different markers. PLWH‐offART presented the highest disturbance of NK‐cells homeostasis and this was not completely restored by long‐term ART. Interestingly, long term spontaneous control of HIV (PLWH‐LTEC group) was associated with a specific profile of NK‐cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p‐value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p‐value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long‐term control of HIV. [ABSTRACT FROM AUTHOR]

Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. Methods: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. Results: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9–97.2), dropping to 77.6% (95%CI 64.7–86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2–90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. Conclusions: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria, found in heterogenous niches, are known for their health-endorsing properties and are in demand as prospective probiotics. Hence, the scientific community around the globe is in continuous search for novel and new potential strains with extensive applicability and minimum risk. In this context, the present study evaluated the efficiency of Lactiplantibacillus plantarum (P2F2) of human origin, a highly autoaggregating and coaggregating (with pathogens) strain, for its colonization, growth promotion, and immunomodulation. Results indicated moderate hydrophobicity on adhesion to xylene and n-hexadecane and weak electron-donating properties with chloroform. The biofilm of P2F2 formed on polystyrene was strong and highly correlated to exopolysaccharide production. The autoaggregation was moderately correlated with hydrophobicity and biofilm production. It was noted that the P2F2 strain modulated the gut microbiota and increased intestinal villi length in Wistar rats. The lipid and glucose profiles remained intact. P2F2 treatment increased the activity of reactive oxygen species-generating cells in the peritoneal cavity, besides augmenting the mitogen-induced splenocyte proliferation and maintained the immunoglobulins at the normal level. Results from this study conclusively suggest that the strain P2F2 adheres to the intestine and modulates the gut ecosystem besides enhancing cell-mediated immunity without altering the serological parameters tested. [ABSTRACT FROM AUTHOR]

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed. [ABSTRACT FROM AUTHOR]

Objective: Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously. Methods : Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively. Results: Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10. Conclusion: Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation. [ABSTRACT FROM AUTHOR]

Despite the rapid development of vaccines against COVID-19, they have important limitations, such as safety issues, the scope of their efficacy, and the induction of mucosal immunity. The present study proposes a potential component for a new generation of vaccines. The recombinant nucleocapsid (N) protein from the SARS-CoV-2 Delta variant was combined with the ODN-39M, a synthetic 39 mer unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), used as an adjuvant. The evaluation of its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced a systemic cross-reactive, cell-mediated immunity (CMI). In turn, this combination was able to induce anti-N IgA in the lungs, which, along with the specific IgG in sera and CMI in the spleen, was cross-reactive against the nucleocapsid protein of SARS-CoV-1. Furthermore, the nasal administration of the N + ODN-39M preparation, combined with RBD Delta protein, enhanced the local and systemic immune response against RBD, with a neutralizing capacity. Results make the N + ODN-39M preparation a suitable component for a future intranasal vaccine with broader functionality against Sarbecoviruses. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life. [ABSTRACT FROM AUTHOR]

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation. [ABSTRACT FROM AUTHOR]

Background: Currently approved vaccines are highly effective in protecting against hospitalization and severe COVID-19 infections. How pre-existing immunity responds to new variants with mutated antigens is crucial information for elucidating the functional interplay between antibodies and B and T cell responses during infection with new SARS-CoV-2 variants. Methods: In this study, we monitored the dynamics and persistence of the immune response versus different SARS-CoV-2 variants of concern that emerged during the pandemic period (2021–2022) in a cohort of vaccinated healthcare workers, who experienced breakthrough infection in the Pre-Delta, Delta, and Omicron waves. We evaluated both the humoral and cell-mediated responses after infection. We also evaluated the anti-SARS-CoV-2 antibodies levels produced by infection in comparison with those produced after vaccination. Results: Our results highlighted that the immune response against the Delta VOC mainly involved an adaptive humoral and switched memory B cells component, even 3 months after the last vaccine dose, conversely showing a high percentage of depleted adaptive T cells. Omicron infections triggered a consistent production of non-vaccine-associated anti-N antibodies, probably to balance the spike epitope immune escape mechanisms. Conclusion: Our results suggest a direct dependence between the VOC and different humoral and B and T cell balances in the post-infection period, despite the administration of a different number of vaccine doses and the elapsed time since the last vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers are critical complications of uncontrolled diabetes, with peripheral neuropathy, peripheral arterial disease, and immune suppression as primary contributing factors. Adenosine Deaminase (ADA), an enzyme, has been identified as a promising marker for cell-mediated immunity. Its estimation may serve as a predictive marker for immunomodulation, which, in turn, leads to complications among individuals with diabetes. Aim: To estimate serum ADA levels in diabetic patients without diabetic foot and diabetic patients with diabetic foot. Additionally, the study aimed to investigate the association of ADA serum levels with glucose, Glycated Haemoglobin (HbA1c), and the severity of wounds. Materials and Methods: This cross-sectional study was conducted in the central laboratory Department of Biochemistry at Krishna Rajendra Hospital (KR Hospital), Mysuru Medical College and Research Institute, Mysuru, India, from August to September 2021. The study included diabetic foot cases (n=45) and Type 2 diabetes patients on regular follow-up in the Department of Medicine without diabetic foot and any other complications (n=45). Venous blood samples were analysed for ADA, glucose, HbA1c, and complete blood count. The data were statistically analysed using the Mann-Whitney U test, Kruskal-Wallis test, and Spearman rank correlation test. Results: The present study observed a higher incidence of diabetic foot among males. It showed a statistically significant increase in serum ADA, HbA1C, and neutrophil count in patients with diabetic foot compared to patients with diabetes without diabetic foot ulcers, with mean Standard Deviation (SD) of 71.79±25.11, 11.53±3.11%, and 75.91±9.77%, respectively. Serum ADA exhibited a positive correlation with HbA1C and different grades of ulcers. Conclusion: The present study demonstrated a significantly increased serum ADA in diabetic ulcers and a positive correlation with different grades of ulcers. This finding contributes to a better understanding of the disease's pathogenesis at different stages. Furthermore, the positive correlation between ADA and HbA1C levels may play an important role in predicting the glycaemic and immunological status of these patients.

Abstract Background Immunological abnormalities are implicated in the pathogenesis of many chronic diseases. Due to the drug-related adverse effects of currently available orthodox immunomodulators, natural immunomodulators are being looked upon as potential agents to replace them in therapeutic regimens. This research aimed to investigate the immunomodulatory potential of L. micranthus extracts epiphytic on Psidium guajava (LMPGE) and Parkia biglobosa (LMPBE). Methods Phytochemical screening and acute toxicity testing were carried out to identify the phytoconstituents and safety profiles of the extracts. The extracts’ innate and adaptive immunomodulatory potentials were determined in experimental animals using in vivo leucocyte mobilization, delayed-type hypersensitivity (DTH) response, hemagglutination antibody titre, and cyclophosphamide-induced myelosuppression models. Levamisole was used as the standard drug throughout the study. Results Compared to LMPBE, LMPGE contained significantly (p

Cell-mediated immunity (CMI) is crucial in controlling the highly aggressive and progressive SARS-CoV-2 infection. Despite extensive researches on severe COVID-19 infection, the etiology and/or mechanisms of lymphopenia, decreased T cell-mediated responses in patients, cytokine release storms (CRS), and enhanced pro-inflammatory mediators are not fully understood. Several T cell subpopulations, including innate-like lymphocytes (ILLs) and conventional T cells, are involved in COVID-19 infection; however, their contribution to immunity and complications remains to be more elucidated. CD16+ T cells are among the effective players in the development of T helper1 (Th1) responses in COVID-19 infection, while their robust cytolytic properties contribute to lung tissue damage. While CD56-CD16bright NK cells play a protective role, natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells and their roles in COVID-19 require further investigation. The involvement of the other T cell subsets, such as Th17, along with neutrophils, adds to the complexity of the situation. In this review, we presented and discussed the findings of recent studies on T cell responses and the contribution of each type of immune cells to COVID-19.

Background The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Methods In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, −0.1; 95% confidence interval [CI], −13.0% to 12.7%; P =.064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P <.001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. Clinical Trials Registration NCT02538172. [ABSTRACT FROM AUTHOR]

Background In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 μg RSVPreF3-AS01E formulation. Methods In total, 122 older adults (60–80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 μg RSVPreF3 antigen), received an additional 120 μg RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 μg RSVPreF3-AS01E doses until 1 month after dose 3. Results Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1. Conclusions Revaccination with 120 μg RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults. Clinical Trials Registration NCT04657198; EudraCT, 2020-000692-21. [ABSTRACT FROM AUTHOR]

The live-attenuated influenza vaccine (LAIV) has generally been more efficacious than the inactivated vaccine in children. However, LAIV is not recommended for HIV-infected children because of insufficient data. We compared cellular, humoral, and mucosal immune responses to the 2013-2014 LAIV quadrivalent (LAIV4) in HIV-infected and uninfected children 2-25 years of age (yoa). We analyzed the responses to the vaccine H1N1 (H1N1-09), to the circulating H1N1 (H1N1-14), which had significant mutations compared to H1N1-09 and to B Yamagata (BY), which had the highest effectiveness in 2013-2014. Forty-six HIV-infected and 56 uninfected participants with prior influenza immunization had blood and nasal swabs collected before and after LAIV4 for IFNγ T and IgG/IgA memory B-cell responses (ELISPOT), plasma antibodies [hemagglutination inhibition (HAI) and microneutralization (MN)], and mucosal IgA (ELISA). The HIV-infected participants had median CD4+ T cells = 645 cells/µL and plasma HIV RNA = 20 copies/mL. Eighty-four percent were on combination anti-retroviral therapy. Regardless of HIV status, significant increases in T-cell responses were observed against BY, but not against H1N1-09. H1N1-09 T-cell immunity was higher than H1N1-14 both before and after vaccination. LAIV4 significantly increased memory IgG B-cell immunity against H1N1-14 and BY in uninfected, but not in HIV-infected participants. Regardless of HIV status, H1N1-09 memory IgG B-cell immunity was higher than H1N1-14 and lower than BY. There were significant HAI titer increases after vaccination in all groups and against all viruses. However, H1N1-14 MN titers were significantly lower than H1N1-09 before and after vaccination overall and in HIV-uninfected vaccinees. Regardless of HIV status, LAIV4 increased nasal IgA concentrations against all viruses. The fold-increase in H1N1-09 IgA was lower than BY. Overall, participants <9 yoa had decreased BY-specific HAI and nasal IgA responses to LAIV4. In conclusion, HIV-infected and uninfected children and youth had comparable responses to LAIV4. H1N1-09 immune responses were lower than BY and higher than H1N1-14, suggesting that both antigenic mismatches between circulating and vaccine H1N1 and lower immunogenicity of the H1N1 vaccine strain may have contributed to the decreased H1N1 effectiveness of 2013-2014 LAIV4. [ABSTRACT FROM AUTHOR]

Objectives B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. Methods Serum and whole blood samples were collected from RTX-treated rheumatic patients 3–6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. Results Sixty patients were studied after a median (IQR) of 179 (117–221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4–10.75) vs 11 (6.75–14.75) grams, (P  = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2–4) vs 6 (4–8), P  = 0.002] and cumulative dose [4 (3–7) vs 10 (6.25–13) grams, P  = 0.002] and had shorter time from last vaccination to sampling [140 (76–199) vs 192 (128–230) days, P  = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P  = 0.03). Conclusions Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The 2023 International CMV Symposium took place in Barcelona in May 2023. During the 2‐day meeting, delegates and faculty discussed the ongoing challenge of managing the risk of cytomegalovirus infection (the Troll of Transplantation) after solid organ or hematopoietic cell transplantation. Opportunities to improve outcomes of transplant recipients by applying advances in antiviral prophylaxis or pre‐emptive therapy, immunotherapy, and monitoring of cell‐mediated immunity to routine clinical practice were debated and relevant educational clinical cases presented. This review summarizes the presentations, cases, and discussions from the meeting and describes how further advances are needed before the Troll of Transplantation is slain. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in pediatric transplantation. However, currently utilized CMV prevention paradigms have limitations, leading to research aimed at novel strategies for mitigation of CMV infection. Cell-mediated immunity (CMI) is crucial in controlling CMV infection and the use of CMV-specific CMI assays to guide prevention and treatment of CMV infection in both solid organ transplant and hematopoietic cell transplant recipients shows great promise. In this article, we review the immune response to CMV infection to highlight the rationale for CMI assays, describe available commercial assays and strategies for their use, and summarize relevant literature regarding the use of CMI assays in transplant recipients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic introduced significant uncertainty regarding the care of patients with inflammatory bowel disease (IBD). Substantial research efforts have made progress in answering many of the questions that arose, but the constantly shifting paradigm of COVID-19-related research and recommendations has made it challenging for IBD clinicians to remain up-to-date. The goal of this article is to provide a concise and practical summary of the literature evaluating COVID-19 disease risk in addition to COVID-19 vaccine safety, immunogenicity, real-world effectiveness, and uptake among patients with IBD. [ABSTRACT FROM AUTHOR]

Non-specific interferon-gamma (IFN-γ) enzyme-linked immunosorbent (ELISpot) responses after solid organ transplant (SOT) and their relationsh ip with cytomegalovirus (CMV) reactivation have hardly been investigated. Adult kidney transplant (KT) recipients underwent measurement of IFN-γ -producing T cells using the ELISpot assay before and 1 month after transplantation. Data for CMV infection episodes were collected. Risk factors for post-transplant CMV infection, based on IFN-γ responses, were analyzed using a Cox proportional hazards model. A total of 93 KT recipients were enrolled in the study and 84 evaluable participants remained at 1 month post KT. Thirty-three (39%) recipients developed subsequent CMV infection within 6 months post-transplant. At 1-month post-transplant, IFN-γ-producing T cells with <250 spot-forming units (SFUs)/2.5 x 105 peripheral blood mononuclear cells (PBMCs) were significantly associated with CMV infection (HR 3.1, 95% CI 1.4-7.1, p = 0.007). On multivariable analysis, posttransplant IFN-γ-producing T cells with <250 SFUs/2.5 x 105 PBMCs remained independently associated with CMV infection (HR 3.1, 95% C11.2-7.8, p = 0.019). Conclusions: KT recipients with low IFN-γ-producing T cells measured by the ELISpot assay are more likely to develop CMV infection after transplantation. Therefore, measurement of nonspecific cell-mediated immunity ELISpot responses could potentially stratify recipients at risk of CMV infection (Thai Clinical Trials Registry, TCTR20210216004). [ABSTRACT FROM AUTHOR]

Background: Immunological abnormalities are implicated in the pathogenesis of many chronic diseases. Due to the drug-related adverse effects of currently available orthodox immunomodulators, natural immunomodulators are being looked upon as potential agents to replace them in therapeutic regimens. This research aimed to investigate the immunomodulatory potential of L. micranthus extracts epiphytic on Psidium guajava (LMPGE) and Parkia biglobosa (LMPBE). Methods: Phytochemical screening and acute toxicity testing were carried out to identify the phytoconstituents and safety profiles of the extracts. The extracts' innate and adaptive immunomodulatory potentials were determined in experimental animals using in vivo leucocyte mobilization, delayed-type hypersensitivity (DTH) response, hemagglutination antibody titre, and cyclophosphamide-induced myelosuppression models. Levamisole was used as the standard drug throughout the study. Results: Compared to LMPBE, LMPGE contained significantly (p < 0.05) more tannins, cyanogenic glycosides, saponins, reducing sugars, glycosides, flavonoids, and alkaloids. Furthermore, the groups treated with the extracts had a significant (p < 0.05) increase in the total number of leucocytes, neutrophils, basophils, and antibody titers relative to the untreated control. In the same way, the treatment raised TLC in cyclophosphamide-intoxicated rats, with 250 mg/kg b. w. of LMPGE and LMPBE recording 9712.50 ± 178.00 and 8000.00 ± 105.00 × 109 /L, respectively, compared to 3425.00 ± 2 5.00 × 109 /L in the untreated group. Overall, LMPGE was more effective. Conclusions: The findings from this study suggest that L. micranthus epiphytic in Psidium guajava and Parkia biglobosa has possible immune stimulating potential. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers are critical complications of uncontrolled diabetes, with peripheral neuropathy, peripheral arterial disease, and immune suppression as primary contributing factors. Adenosine Deaminase (ADA), an enzyme, has been identified as a promising marker for cell-mediated immunity. Its estimation may serve as a predictive marker for immunomodulation, which, in turn, leads to complications among individuals with diabetes. Aim: To estimate serum ADA levels in diabetic patients without diabetic foot and diabetic patients with diabetic foot. Additionally, the study aimed to investigate the association of ADA serum levels with glucose, Glycated Haemoglobin (HbA1c), and the severity of wounds. Materials and Methods: This cross-sectional study was conducted in the central laboratory Department of Biochemistry at Krishna Rajendra Hospital (KR Hospital), Mysuru Medical College and Research Institute, Mysuru, India, from August to September 2021. The study included diabetic foot cases (n=45) and Type 2 diabetes patients on regular follow-up in the Department of Medicine without diabetic foot and any other complications (n=45). Venous blood samples were analysed for ADA, glucose, HbA1c, and complete blood count. The data were statistically analysed using the Mann-Whitney U test, Kruskal-Wallis test, and Spearman rank correlation test. Results: The present study observed a higher incidence of diabetic foot among males. It showed a statistically significant increase in serum ADA, HbA1C, and neutrophil count in patients with diabetic foot compared to patients with diabetes without diabetic foot ulcers, with mean Standard Deviation (SD) of 71.79±25.11, 11.53±3.11%, and 75.91±9.77%, respectively. Serum ADA exhibited a positive correlation with HbA1C and different grades of ulcers. Conclusion: The present study demonstrated a significantly increased serum ADA in diabetic ulcers and a positive correlation with different grades of ulcers. This finding contributes to a better understanding of the disease's pathogenesis at different stages. Furthermore, the positive correlation between ADA and HbA1C levels may play an important role in predicting the glycaemic and immunological status of these patients. [ABSTRACT FROM AUTHOR]

Background There is little information on cell-mediated immunity (CMI) to COVID-19 mRNA vaccines in children. We studied adaptive and innate CMI in vaccinated children aged 6 to 60 months. Methods Blood obtained from participants in a randomized placebo-controlled trial of an mRNA vaccine before and 1 month after the first dose was used for antibody measurements and CMI (flow cytometry). Results We enrolled 29 children with a mean age of 28.5 months (SD, 15.7). Antibody studies revealed that 10 participants were infected with SARS-CoV-2 prevaccination. Ex vivo stimulation of peripheral blood mononuclear cells with SARS-CoV-2 spike peptides showed significant increases pre- to postimmunization of activated conventional CD4+ and γδ T cells, natural killer cells, monocytes, and conventional dendritic cells but not mucosa-associated innate T cells. Conventional T-cell, monocyte, and conventional dendritic cell responses in children were higher immediately after vaccination than after SARS-CoV-2 infection. The fold increase in CMI pre- to postvaccination did not differ between children previously infected with SARS-CoV-2 and those uninfected. Conclusions Children aged 6 to 60 months who were vaccinated with a COVID-19 mRNA vaccine developed robust CMI responses, including adaptive and innate immunity. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell‐mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment. Methods: We serially assessed CMV CMI using the QuantiFERON‐CMV assay (QF‐CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post‐prophylaxis CMV infection and post‐treatment relapse, respectively. Results: Only one (4.2%) of 24 CMV D+/R‐ patients demonstrated positive QF‐CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post‐prophylaxis CMV infection; all four had undetectable QF‐CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF‐CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p =.0036). Conclusion: Since CMV D+/R‐ SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: Recurrence after Cytomegalovirus (CMV) infection in heart transplant recipients is difficult to predict, in spite of its high incidence. Secondary prophylaxis could reduce this burden; however, its duration remains unestablished. We evaluated the QuantiFERON®‐CMV test to see if it could predict CMV recurrence and help optimize the duration of secondary prophylaxis. Methods: This observational retrospective single center study included all heart transplant recipients who developed CMV infection between 2019 and 2021, with the CD8+ T‐cell‐mediated CMV immunity QuantiFERON®‐CMV test assessed at the time of (val)ganciclovir curative treatment completion. The main outcomes were CMV recurrence and duration of secondary prophylaxis. Secondary outcomes included immunosuppressive regimen, rejection, lymphocyte count, CMV viral load, infection type, and duration as possible confounding factors for recurrence. Results: Among the 15 patients included, five (33%) experienced recurrence, of whom three (60%) had a positive QuantiFERON®‐CMV test. The duration of secondary prophylaxis was similar regardless of QF‐CMV positivity. No confounding factor was significantly associated with CMV recurrence; however, it occurred in only 1/7 (14%) of the patients receiving an everolimus‐containing immunosuppressive regimen. Conclusion: In the population of heart transplant recipients, most of whom received ATG‐based induction, the QuantiFERON®‐CMV assay may not accurately predict CMV recurrence and would have not helped refining the duration of secondary prophylaxis in our patients. Other cell‐mediated immunity tests and strategies in this specific population, including everolimus‐containing regimens, may help predict and manage CMV recurrence. [ABSTRACT FROM AUTHOR]

Selecting high-immune-responding cattle benefits the individual animal and the herd. To assess factors that have a role in determining the immune status of cattle, this study used 55 weaned bull and 57 weaned heifer Brahman calves. Antibody-mediated immune response (AMIR) was determined by using a vaccine-specific IgG, enzyme-linked immunosorbent assay (ELISA) in response to cattle receiving the Salmonella Newport Extract vaccine. Cell-mediated immune response (CMIR) was determined by using a subcutaneous (neck) sensitization dose of Candida albicans (CA) with Quil-A adjuvant on Day 0. On Day 14, caudal skinfold thickness (SFT) was measured using Harpenden calipers prior to the intradermal injection of CA into the skinfold, and on Day 15, the injection site SFT was measured again. The response was determined by using the difference in SFT from Day 15 (post-injection) and Day 14 (pre-injection). In weaned Brahman calves, AMIR was not influenced by sex; however, there was sexual dimorphism associated with CMIR, in that bull calves had a greater response than heifers (p < 0.05). Our studies demonstrate that weaned Brahman calves can be separated into AMIR and CMIR classes and that AMIR and CMIR should be investigated further as selection tools in beef cattle production. [ABSTRACT FROM AUTHOR]

Background. Congenital ichthyoses (CIs) are a heterogeneous clinical-etiological group of genodermatoses. Typical clinical symptoms of this disease, regardless of the form, are generalized erythroderma, peeling, itching, hyperkeratosis, severe structural and functional disorders of the epidermal barrier, other organs and systems. Patients have an extremely low quality of life due to changes in appearance, discomfort, constant disease symptoms. Thus far, there are no effective treatment methods for ichthyosis. That is why scientific search for new therapies is the topical issue in pediatrics and pediatric dermatology.Objective. The aim of the study is to examine the cell-mediated immunity state in patients with CI via assessment of the pattern of lymphocyte subpopulations in peripheral blood. The research was conducted to study the content of the main and small lymphocyte subpopulations in 86 patients with established diagnosis of CI aged from 1 month to 18 years. The diagnosis was made according to the clinical data and the results of molecular genetic testing. Comparative analysis of blood immunological indicators in children with CI and in patients with other immunemediated chronic dermatoses: atopic dermatitis (AD; n = 68) and psoriasis vulgaris (n = 55).Methods. The level of T lymphocytes, T helpers (Th), cytotoxic T lymphocytes (Tc), B lymphocytes, NK cells, Treg-cells (Treg), activated T helpers (Thact), Th17 lymphocytes in peripheral blood was evaluated via flow cytometry using monoclonal antibodies. Statistical analysis was performed via Statistica 10.0. Differences between the groups were assessed via Mann-Whitney non-parametric test, differences were considered significant at p < 0.05.Results. A significant increase of activated T-helpers level in peripheral blood was revealed in patients with CI and psoriasis compared to children with AD (p < 0.001), as well as an increased levels of B-lymphocytes and Treg in children with CI (p < 0.05).Conclusion. Children with CI have shown some features of cell-mediated immunity such as: pathological activation of Th lymphocytes, impaired terminal differentiation of naive CD4+ cells to Thact, Treg, Th17 lymphocytes and their proliferation. Comparative analysis of mentioned immunological indicators in children with CI, psoriasis and AD has shown comparable results of increased Thact lymphocytes levels in patients in CI and psoriasis groups. This results open up potential of using immunobiological drugs of psoriasis target therapy within the new management strategy for children with CI.

Selecting high-immune-responding cattle benefits the individual animal and the herd. To assess factors that have a role in determining the immune status of cattle, this study used 55 weaned bull and 57 weaned heifer Brahman calves. Antibody-mediated immune response (AMIR) was determined by using a vaccine-specific IgG, enzyme-linked immunosorbent assay (ELISA) in response to cattle receiving the Salmonella Newport Extract vaccine. Cell-mediated immune response (CMIR) was determined by using a subcutaneous (neck) sensitization dose of Candida albicans (CA) with Quil-A adjuvant on Day 0. On Day 14, caudal skinfold thickness (SFT) was measured using Harpenden calipers prior to the intradermal injection of CA into the skinfold, and on Day 15, the injection site SFT was measured again. The response was determined by using the difference in SFT from Day 15 (post-injection) and Day 14 (pre-injection). In weaned Brahman calves, AMIR was not influenced by sex; however, there was sexual dimorphism associated with CMIR, in that bull calves had a greater response than heifers (p < 0.05). Our studies demonstrate that weaned Brahman calves can be separated into AMIR and CMIR classes and that AMIR and CMIR should be investigated further as selection tools in beef cattle production.

Introduction: Rhinosporidiosis is an enigmatic disease with many unsolved queries right from taxonomy to treatment. This study has been done to understand the disease characteristics with a peek into the lesser known immunological aspects of it by studying the changes in levels of certain primarily cell-mediated immunity (CMI)-specific cytokines in rhinosporidiosis patients.Materials and Methods:A prospective observational study was performed. Detailed epidemiological and clinicoradiological assessment was done along with selected inflammatory and immunological markers. The tests for immunological parameters were done by ELISA and CLIA and data were compiled and analyzed using appropriate statistics.Results:Disease showed male predominance and all patients gave a universal pond bathing history. Majority patients had O+ve blood group. Right side was affected most with nasal obstruction being commonest symptom. Nasal cavity was involved in majority of cases with inferior turbinate and meatus being sites of maximum occurrence and attachment. Nasopharynx, oropharynx were other involved sites. Extra-nasal sites included skin and parotid gland. Endoscopic and CECT findings were similar and confirmed intraoperatively. Tests for inflammatory markers showed no significant change in patients. Immunological markers -IL-6, TNF-beta- levels showed significant increase though no such increase was found with IFN-gamma levels.Conclusion:Rhinosporidiosis has a definite epidemiological and clinical-radiological profile. A clear association with exposure to contaminated water is present which could not be further associated with disease duration or recurrence. The immunological profile needs to be further investigated upon since it remains quite elusive.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

Neutrophils are believed to play a role in the initial stages of paratuberculosis, and it has recently been demonstrated that vaccination can modulate their function via priming or through epigenetic and metabolic reprogramming (training). Modulation of the neutrophil response against Mycobacterium avium subspecies paratuberculosis (Map) through vaccination has been demonstrated in a rabbit model but not in ruminants. Therefore, in the present work, the effect of vaccination on the response of caprine neutrophils against Map was studied. Neutrophils were isolated from non-vaccinated (n = 7) and Gudair®-vaccinated goat kids (n = 7), before vaccination and 30 days post-vaccination. Then, several neutrophil functions were quantified ex vivo: cell-free and anchored neutrophil extracellular trap (NET) release, phagocytosis, and the differential expression of several cytokines and TLR2. The induction of cell-free NETosis and TLR2 expression by Map is reported for the first time. However, vaccination showed no significant effect on any of the functions studied. This suggests that the protection conferred by Gudair® vaccination is based on mechanisms that are independent of the neutrophil function modulation. Further research into the impact of alternative vaccination strategies or the paratuberculosis infection stage on ruminant neutrophil function could provide valuable insights into its role in paratuberculosis.