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Plasmodium vivax, a challenging species to eliminate, causes millions of malaria cases globally annually. Developing an effective vaccine is crucial in the fight against vivax malaria, but considering the limited number of studies focusing on the identification and development of P. vivax-specific vaccine candidates, exploring new antigens is an urgent need. The merozoite protein CyRPA is essential for P. falciparum growth and erythrocyte invasion and corresponds to a promising candidate antigen. In P. vivax, a single study with multiple vaccine candidates indicates PvCyRPA with strong association with protection, outperforming classic malaria vaccine candidates. However, little is known about the specific naturally acquired response in the Americas, as well as the antigen epitope mapping. For this reason, we aimed to investigate the cellular and humoral immune response elicited against PvCyRPA in Brazilian endemic areas to identify the existence of immunodominant regions and the potential of this protein as a single or even a multi-stage specific malaria vaccine candidate for P. vivax. The results demonstrated that PvCyRPA is naturally immunogenic in Brazilian Amazon individuals previously exposed to malaria, which presented anti-PvCyRPA cytophilic antibodies. Moreover, our data show that the protein also possesses important immunogenic regions with an overlap of B and T cell epitopes. These data reinforce the possibility of including PvCyRPA in vaccine formulations for P. vivax. [ABSTRACT FROM AUTHOR]

The effectiveness of Toll‐like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti‐tumor immunity. To address that, the common nutrient metal ions are explored (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING‐NF‐κB pathway. Mn2+ and CpG are then self‐assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma‐bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2‐type tumor‐associated macrophages (TAMs) to an M1‐type and boosting intra‐tumoral infiltration of CD8+/CD4+ T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen‐specific cytotoxic CD8+ T cell immune response and humoral immunity. In a prophylactic tumor‐bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16‐OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors. [ABSTRACT FROM AUTHOR]

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs. [ABSTRACT FROM AUTHOR]

Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection. [ABSTRACT FROM AUTHOR]

Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein–directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti–spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2–infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection. Editor's summary: Monoclonal antibody (mAb) therapies and vaccines were both essential tools for curbing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. As vaccines were rolled out during clinical trials for mAb therapies, it offered Petro et al. a unique opportunity to ask how SARS-CoV-2 mAb therapy influenced vaccine responses. The authors found that mAb therapy with casirivimab plus imdevimab, given at the time of vaccination, altered vaccine-elicited immunity in humans, resulting in lower neutralizing titers; this observation was mirrored in data from both nonhuman primates and mice. Encouragingly, booster vaccinations restored neutralizing antibody titers. A similar study in humans who received casirivimab plus imdevimab during SARS-CoV-2 infection revealed that early mAb treatment also impaired elicitation of endogenous immunity. Together, these data shed light on the complex interplay among mAb therapies, vaccines, and infections. —Courtney Malo [ABSTRACT FROM AUTHOR]

The article discusses the potential role of colchicine in treating Oral Mucous Membrane Pemphigoid (MMP), an autoimmune disease affecting the oral cavity. While corticosteroids are the first-line treatment, colchicine showed promising results in patients resistant to other therapies. A retrospective study at Bordeaux University Hospital found that colchicine led to remission in oral MMP lesions, with fewer adverse effects compared to dapsone. Further research is needed to confirm these findings and establish colchicine as a viable second-line treatment option for MMP. [Extracted from the article]

Background: Plasmodium vivax infection, when it occurs during pregnancy, has often been associated with serious adverse pregnancy outcomes. However, immunological alterations in pregnancy and their consequences have been little explored. We characterized the humoral immune response in pregnant women exposed to malaria by P. vivax antigens and its association with the maternal inflammatory profile and poor pregnancy outcomes. Methods: An observational cohort study in the Brazilian Amazon was conducted between 2013 and 2015. After applying exclusion criteria, 242 mother-child pairs were included in the analysis. Data on maternal infection, gestational outcomes, and inflammatory factors were evaluated in the maternal peripheral plasma. In samples from the first infection, the presence of total IgG and its subclasses in plasma against PvMSP119 protein were also quantified. Results: Previous exposure to malaria, observed by anti-total IgG antibodies to the PvMSP119 antigen, increased the inflammatory response to infection when the pregnant woman had malaria during pregnancy. IL-6 and IL-10 levels were positively correlated with parasitemia and with total IgG levels; but they were negatively correlated with the gestational age at delivery from Pv-infected woman. In multivariate linear regression analyses, IgG 1, 2 and 4 was negatively and positively associated with cytokines IL-6 and IL-10, respectively, in P. vivax-infection. Conclusions: An association between the humoral immune response and the peripheral inflammatory cytokine profile with the adverse outcomes in malaria in pregnancy by P. vivax was observed. Previous exposure to the parasite can influence the IL-6 and IL-10 response, which is associated with increased parasitemia, reduced maternal weight gain and premature delivery. Author summary: Plasmodium vivax malaria in pregnancy is also associated with several adverse outcomes, even in low-transmission regions such as South America. However, to our knowledge, no study has previously investigated the link between the humoral immune response due to previous exposure to P. vivax and the immunological profile during pregnancy infection and its association with poor pregnancy outcomes. In this study, after applying exclusion criteria, 242 mother-child pairs were evaluated for different immunological markers of malaria exposure in an endemic area in the Brazilian Amazon. We showed that previous exposure to P. vivax, through the humoral immune response to the PvMSP119 antigen, can exacerbate the inflammatory response during gestational malaria and is associated with increased parasitemia, reduced maternal weight gain and premature delivery. These findings help to understand the association between anti-PvMSP119 antibodies, considered exposure marker, and the maternal peripheral inflammatory profile throughout pregnancy, bringing important implications for understanding the immunobiology of the disease. [ABSTRACT FROM AUTHOR]

Seasonal and pandemic influenza infection present a potential threat to patients with antibody deficiency. The acceptance and effect of the current recommendation for annual vaccination against influenza for patients with antibody deficiency is not well investigated and due to antigenic drift or shift the protective capacity of regular IgG replacement therapy (IgRT) is considered low. This narrative review considers the effect of influenza vaccination in immunodeficient patients and discusses available information on the effect of immunoglobulin products on seasonal influenza infectivity and severity in antibody deficiency patients receiving IgRT. The humoral immune response to seasonal influenza vaccination is reduced in patients with antibody immune deficiency. However, there is no evidence that the proportion of patients with primary antibody deficiency who develop influenza illness, and the severity of such illness, is increased when compared with the general population. The IgRT that patients receive has been shown to contain neutralizing antibodies as a consequence of past flu infections against both the hemagglutinin and neuraminidase surface proteins and other viral internal proteins of different influenza A virus strains. Studies have demonstrated not only significant levels of specific but also cross-reactive antibodies against seasonal influenza virus strains. Thus, despite the yearly changes in influenza viral antigenicity that occur, IgRT could potentially contribute to the protection of patients against seasonal influenza. Currently, only limited clinical data are available confirming a preventative effect of IgRT with respect to seasonal influenza infection. In conclusion, there is some evidence that IgRT could contribute to protection against seasonal influenza in patients with antibody-related immunodeficiency. However, additional clinical data are needed to confirm the extent and relevance of this protection and identify the main responsible virus targets of that protection. [ABSTRACT FROM AUTHOR]

Background: Stress associated with changes in host immunity occurs in response to altered environmental conditions, endogenous imbalances, infectious agents and harmful stimuli. The importance of genetic diversity in chickens has increased due to individual immune differences towards resistance and susceptibility to various stimuli. Objectives: This study aimed to investigate the association of major histocompatibility complex (MHC) polymorphism with acute phase response (APR) in Ross 308 broiler chickens. Methods: The allelic diversity of the LEI0258 microsatellite marker was determined in 120 Ross broilers. In addition, acute phase proteins (APPs), including serum amyloid A (SAA) and alpha‐1‐acid glycoprotein (AGP), were analysed as markers of the APR. Furthermore, leukocyte count and the heterophil/lymphocyte ratio (H/L ratio) were examined. The antibody response to the Newcastle disease vaccine (NDV) was also measured to assess humoral mediated immunity. Lastly, the correlation between immune responses and MHC alleles was investigated to identify the most effective alleles in a stress‐related situation. Results: A total of six alleles, ranging from 195 to 448 bp, were identified. Association study revealed a significant influence of MHC alleles on APPs in Ross population (p < 0.05). Notably, Allele 448 had a significant correlation with SAA concentration and the H/L ratio. Allele 207 displayed a positive association with AGP concentration, whereas Allele 195 showed a negative association. Furthermore, a significant association was observed between Allele 448 and basopenia, as well as between Allele 195 and monocytosis. Conclusions: Results confirmed the significance of MHC as a candidate gene marker for immune responses, which supports its use for vaccine design, genetic improvement of disease‐resistant traits and resource conservation in commercial broiler chickens. [ABSTRACT FROM AUTHOR]

Lymph node (LN)‐resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen‐presenting capabilities and proximity to a high concentration of immune cells. Direct intra‐LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs. Herein, we describe a novel vaccination platform in which two complementary multi‐arm poly(ethylene glycol) (PEG) polymers—one covalently bound to the model antigen ovalbumin (OVA)—are injected subcutaneously into two distinct sites. These materials then drain to the same LN through different lymphatic vessels and, upon meeting in the LN, rapidly crosslink. This system improves OVA delivery to, and residence time within, the draining LN compared to all control groups. The crosslinking of the two PEG components also improves humoral immunity without the need for any pathogen‐mimicking adjuvants. Further, we observed a significant increase in non‐B/T lymphocytes in LNs cross‐presenting the OVA peptide SIINFEKL on MHC I over a dose‐matched control containing alum, the most common clinical adjuvant, as well as an increase in DC activation in the LN. These data suggest that this platform can be used to deliver antigens to LN‐resident immune cells to produce a stronger humoral and cellular immune response over materials‐matched controls without the use of traditional adjuvants. [ABSTRACT FROM AUTHOR]

Background: The effects of COVID‐19 vaccines on immunocompromised people such as hemodialysis (HD) patients are an important topic that should be addressed. This study reports an observation of the effect of the third dose of the Sinopharm vaccine (SphV3) on the level of hepatitis B surface antibody (anti‐HBs) in HD patients, and the differences between anti‐HBs titers before and after SphV3 were analytically evaluated. Methods: This single‐center observational study involved all HD patients presented to Shariati Hospital, Tehran, Iran, from February 2021 to March 2022. All patients received three doses of the Sinopharm vaccine over 8 months. The anti‐HBs level is measured every 6 months as the routine evaluation against HBV infection for all HD patients. Three months before (anti‐HBs‐B3) and 3 months after (anti‐HBs‐A3) SphV3 were the routine times to measure the anti‐HBs titer during this study. Results: Twenty‐five HD patients were enrolled. Overall, the anti‐HBs‐A3 was significantly higher than anti‐HBs‐B3 (p = 0.001). The anti‐HBs levels before and after SphV3 were not statistically remarkable in patients with diabetes and ischemic heart disease. The patients with a history of kidney transplant and those with a history of COVID‐19 had significant differences between anti‐HBs‐B3 and anti‐HBs‐A3 (p = 0.002, p = 0.003, respectively). Conclusion: Our findings revealed that inactivated COVID‐19 vaccine may be involved in the humoral immune response to hepatitis B in HD patients. It may be novel and have significant implications for the vaccination protocol for immunocompromised patients, including those undergoing HD and transplant recipients. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is a complex and heterogeneous tissue composed of various cell types, including tumor cells, stromal cells, and immune cells, as well as non-cellular elements. Given their pivotal role in humoral immunity, B cells have emerged as promising targets for anti-tumor therapies. The dual nature of B cells, exhibiting both tumor-suppressive and tumor-promoting functions, has garnered significant attention. Understanding the distinct effects of various B cell subsets on different tumors could pave the way for novel targeted tumor therapies. This review provides a comprehensive overview of the heterogeneous B cell subsets and their multifaceted roles in tumorigenesis, as well as the therapeutic potential of targeting B cells in cancer treatment. To develop more effective cancer immunotherapies, it is essential to decipher the heterogeneity of B cells and their roles in shaping the TME. [ABSTRACT FROM AUTHOR]

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Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age =15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities. Methods: To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -postfusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study. Results: Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms. Discussion: This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a datadriven approach. [ABSTRACT FROM AUTHOR]

The germinal center (GC) reaction is crucial for somatic hypermutation, affinity maturation, and the selection of high-affinity B cells, all of which are hallmarks of the humoral immune response. Understanding the distinct roles of various B cell genes is essential for elucidating the selection mechanisms within the GC reaction. Traditionally, studying B cell gene function in the GC reaction involved generating knock-out mice, a highly time-consuming method that necessitates complex vectors. The advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has simplified the creation of knock-out mice. However, even with CRISPR, the generation of knock-out mice still faces challenges, including being time-consuming, costly, having low knockout efficiency, and raising ethical concerns regarding animal use. To address these challenges, we developed an alternative method to traditional knock-out mouse generation. Our approach entails the ex vivo CRISPR editing of B cells from transgenic donor mice with different B cell receptor affinities followed by their adoptive transfer into recipient mice. We present a cost-effective, rapid, versatile, and adaptable CRISPR-Cas9 method for in vivo loss-of-function studies of individual murine B cell genes within the context of the GC reaction. This method provides a valuable tool for investigating the complex roles of different B cell genes in the GC selection process. As proof of concept, we validated our approach by examining the role of the pro-apoptotic gene Fas in the GC selection process. We adoptively transferred a mix of Fas knock-out (FasKO) low-affinity B cells, Fas wild-type (FasWT) low-affinity B cells, and FasWT high-affinity B cells into recipient mice. From our results, FasKO low-affinity B cells were still outcompeted by the FasWT high-affinity B cells for selection in the GC. An important observation was the accumulation of FasKO low-affinity GC B cells when compared to the FasWT low-affinity B cells, which suggested a role of Fas in the GC selection process. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax is the dominant Plasmodium spp. causing malaria throughout tropical and sub-tropical countries. Humoral immunity is induced during P. vivax infection. However, data on longevity of antibody and memory B cell (MBC) responses is lacking. Follicular helper T cells (Tfh) are drivers of high-affinity and long-lived antibody responses. Understanding of Tfh-mediated immunity against malaria is valuable for vaccine development. Methodology/Principal findings: We enrolled 31 acutely infected P. vivax patients in low malaria transmission areas of Thailand to detect frequencies, phenotypes and kinetics of different subsets of circulating Tfh (cTfh) and MBCs, and to evaluate their association with humoral immunity following natural P. vivax infection. Expansion of cTfh2 cells, activated and atypical MBCs were shown during acute malaria. To relate increased cTfh2 cells to humoral immunity, P. vivax-specific MBCs and antibodies were assessed. High anti-PvCSP and -PvDBPII seropositivity was detected and most subjects produced MBCs specific to these antigens. The increased cTfh2 cells were positively related to atypical MBCs, plasmablasts/plasma cells, and anti-PvDBPII IgM and IgG levels. Distributions of memory cTfh cell subsets were altered from central memory (CM) to effector memory (EM) during infection. The highest ratios of cTfh-EM/cTfh-CM were represented in cTfh2 cells. Positive correlation of cTfh17-EM with activated and atypical MBCs was observed, while cTfh2-CM and cTfh17-CM cells were positively related to PvDBPII-specific MBCs and IgM levels. Conclusions/Significance: Present study demonstrated that P. vivax infection induced cTfh polarization into cTfh2 subset, and alteration of memory cTfh2 phenotype from CM to EM phase. These P. vivax-induced cTfh responses significantly associated with generation of MBCs and antibody responses. Therefore, cTfh2 cells might possibly influence humoral immunity by inducing expansion of activated and atypical MBCs, and by generating P. vivax-specific MBCs and antibody responses following natural infection. Author summary: Naturally acquired immunity to malaria relies on the development of MBCs and long-lived plasma cells that serve as the source of antibody responses that inhibit parasite invasion. To date, information is limited regarding the role of Tfh cells in supporting development of MBCs and antibodies against P. vivax infection, particularly in the context of natural malaria exposure. Here, we identified subsets of cTfh cells that involved in the generation of P. vivax-specific MBC and antibody responses. We found that P. vivax infection induced an expansion of cTfh2 cells. The cTfh2 cell responses were positively related to an increased frequency of activated and atypical MBCs, and plasma cells, as well as P. vivax-specific antibody levels. Moreover, phenotype of memory cTfh2 cells was changed from CM to EM phase during infection. The alteration of cTfh17-EM cells was significantly related to expansion of activated and atypical MBCs, while the presence of cTfh2-CM and cTfh17-CM cells was positively related to P. vivax-specific MBCs and IgM responses. Data from this study suggests a role of cTfh2 cells in contribution to the development of P. vivax-specific MBCs and antibody responses. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS‐H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen‐specific T cells. MANS‐H demonstrates even greater effectiveness in the production of antigen‐specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS‐H evokes high frequencies of antigen‐specific Th1 and CD8+ cell immunity, which are comparable with Quil‐A that is widely used in veterinary vaccines. Immunized mice with MANS‐H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory Syncytial Virus (RSV) is a significant cause of respiratory illnesses worldwide, particularly in infants and elderly individuals. Despite the burden RSV imposes, effective preventive measures are limited. The research application of adeno-associated virus (AAV) in vaccine platforms has been expanding, and its potential in prevention and treatment has garnered much attention. Methods: In this study, we explored the potential application of a recombinant adeno-associated virus 5 (rAAV5) vector-based RSV vaccine, focusing on the expression of the pre-fusion (Pre-F) protein structure. Through intramuscular immunization in mice. The immunogenicity of the vaccine was evaluated in Balb/ c mice immunized intramuscularly and intranasal, respectively. Results: The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days postimmunization. Notably, intranasal administration also elicited protective antibodies. Characterization studies confirmed the ability of the vac-cine to express the Pre-F protein and its superior immunogenicity compared to that of full-length F protein. Conclusion: These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted. [ABSTRACT FROM AUTHOR]

Plasmodium vivax malaria causes significant public health problems in endemic regions. Considering the rapid spread of drug-resistant parasite strains and the development of hypnozoites in the liver with potential for relapse, development of a safe and effective vaccine for preventing, controlling, and eliminating the infection is critical. Immunity to malaria is mediated by antibodies that inhibit sporozoite or merozoite invasion into host cells and protect against clinical disease. Epidemiologic data from malaria endemic regions show the presence of naturally acquired antibodies to P. vivax antigens during and following infection. But data on the persistence of these antibodies, development of P. vivax-specific memory B cells (MBCs), and their relation to reduction of malaria severity and risk is limited. This review provides an overview of the acquisition and persistence of naturally acquired humoral immunity to P. vivax infection. Also, we summarize and discuss current progress in assessment of immune responses to candidate vaccine antigens in P. vivax patients from different transmission settings. Longitudinal studies of MBC and antibody responses to these antigens will open new avenues for developing vaccines against malaria infection and its transmission. Author summary: Despite the Plasmodium vivax parasite causing a large proportion of the global malaria burden, it has been neglected by much of the research world. Vaccines that can effectively induce strong and long-lasting antibody and memory B cell (MBC) responses are necessary for disease control and elimination, as they are crucial for blocking subsequent infection. The development and longevity of antibodies and MBC responses against different stages of P. vivax have been studied in various transmission settings. Some candidate antigens have been investigated in clinical trials with promising results. Previous reports have provided evidence of antibody acquisition to representative candidate P. vivax antigens from pre-erythrocytic, blood and transmission stages. However, evidence of durable antibody responses and development of P. vivax-specific MBCs is still lacking. Recently, expansion of atypical MBCs along with up-regulation of inhibitory receptors and reduced BCR signaling has been demonstrated and associated with short-lived antibody responses, culminating in impaired humoral immunity. Collectively, the capacity of P. vivax antigens to induce naturally acquired humoral immunity has been addressed. The results allow optimization of vaccine design to enhance immune responses to the parasite and protect against disease. [ABSTRACT FROM AUTHOR]

The use of fish meal/oil in carnivorous fish feeds remains a concern for the environmental sustainability of aquaculture. In this study, we investigated the impact of an innovative diet designed to be cost‐effective and environmentally sustainable (i.e., 60% replacement of fish meal by a blend of plant, yeast [Saccharomyces cerevisiae], and krill meal feed ingredients) on the growth, health, and welfare of gilthead seabream (Sparus aurata). Over a 135‐day experiment, fish were fed either the innovative or a commercial diet (control), and various parameters were evaluated, namely growth performance, levels of physiological blood parameters related to stress, immunity, health, and welfare, as well as swimming activity, serving as a proxy for energy expenditure. Results revealed that the innovative diet enhanced growth compared to fish fed the control diet. Hematological and biochemical indicators did not highlight any impaired welfare condition in fish fed innovative diet while higher levels of Immunoglobulin M were measured in plasma of fish fed innovative diet, potentially suggesting enhancement of humoral immunity. However, accelerometer tags data revealed that fish fed the innovative diet exhibited higher overall swimming activity, suggesting higher energy expenditure, which was consistent with greater prealbumin levels measured in the plasma. In conclusion, the higher energy metabolism in fish fed the innovative diet might be compensated by the diet's content, which may boost humoral immunity and hence help the fish develop a better adaptation to rearing environment, including its viral and bacterial load, ensuring overall better growth. Longer term investigations, including measurements of additional parameters, are required to validate these promising preliminary outcomes. [ABSTRACT FROM AUTHOR]

COVID-19 convalescent plasma (CCP) was one of the first therapies to receive emergency use authorization for management of COVID-19. We assessed the effectiveness of CCP in a propensity-matched analysis, and whether the presence of antibodies in the recipient at the time of treatment or the titer of antibodies in the administered CCP influenced clinical effectiveness. In an inpatient population within a single large health system, a total of 290 CCP patients were matched to 290 controls. While CCP increased titers of anti-SARS-CoV-2 RBD IgG titers post-CCP (p = <0.0001), no differences in 30-day survival were observed between CCP patients and controls in univariate and multivariate analyses. Survival at 30 days was numerically lower in recipients who were seronegative prior to CCP administration, compared to those with low titer and high titer anti-SARS-CoV-2 RBD IgG, respectively, but did not reach statistical significance (56% vs 82% vs 75%, p = 0.16). Patients who received 2 units of high-titer CCP had numerically better survival versus those who received fewer high-titer units, but this was not statistically significant (p = 0.08). CCP did not improve 30-day survival compared to propensity matched controls. Together these data support that CCP therapy provides limited benefit to hospitalized patients with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Single-domain von Willebrand factor type C (SVWC) constitute a protein family predominantly identified in arthropods, characterized by a SVWC domain and involved in diverse physiological processes such as host defense, stress resistance, and nutrient metabolism. Nevertheless, the physiological mechanisms underlying these functions remain inadequately comprehended. Results: A massive expansion of the SVWC gene family in Musca domestica (MdSVWC) was discovered, with a count of 35. MdSVWC1 was selected as the representative of the SVWC family for functional analysis, which led to the identification of the immune function of MdSVWC1 as a novel pattern recognition receptor. MdSVWC1 is highly expressed in both the fat body and intestines and displays acute induction upon bacterial infection. Recombinant MdSVWC1 binds to surfaces of both bacteria and yeast through the recognition of multiple pathogen-associated molecular patterns and exhibits Ca2+-dependent agglutination activity. MdSVWC1 mutant flies exhibited elevated mortality and hindered bacterial elimination following bacterial infection as a result of reduced hemocyte phagocytic capability and weakened expression of antimicrobial peptide (AMP) genes. In contrast, administration of recombinant MdSVWC1 provided protection to flies from bacterial challenges by promoting phagocytosis and AMP genes expression, thereby preventing bacterial colonization. MdSPN16, a serine protease inhibitor, was identified as a target protein of MdSVWC1. It was postulated that the interaction of MdSVWC1 with MdSPN16 would result in the activation of an extracellular proteolytic cascade, which would then initiate the Toll signaling pathway and facilitate the expression of AMP genes. Conclusions: MdSVWC1 displays activity as a soluble pattern recognition receptor that regulates cellular and humoral immunity by recognizing microbial components and facilitating host defense. [ABSTRACT FROM AUTHOR]

Our previous study has found that monoclonal antibodies targeting a conserved epitope peptide spanning from residues 1144 to 1156 of SARS-CoV-2 spike (S) protein, namely S(1144–1156), can broadly neutralize all of the prevalent SARS-CoV-2 strains, including the wild type, Alpha, Epsilon, Delta, and Gamma variants. In the study, S(1144–1156) was conjugated with bovine serum albumin (BSA) and formulated with Montanide ISA 51 adjuvant for inoculation in BALB/c mice to study its potential as a vaccine candidate. Results showed that the titers of S protein-specific IgGs and the neutralizing antibodies in mouse sera against various SARS-CoV-2 variants, including the Omicron sublineages, were largely induced along with three doses of immunization. The significant release of IFN-γ and IL-2 was also observed by ELISpot assays through stimulating vaccinated mouse splenocytes with the S(1144–1156) peptide. Furthermore, the vaccination of the S(1143–1157)- and S(1142–1158)-EGFP fusion proteins can elicit more SARS-CoV-2 neutralizing antibodies in mouse sera than the S(1144–1156)-EGFP fusion protein. Interestingly, the antisera collected from mice inoculated with the S(1144–1156) peptide vaccine exhibited better efficacy for neutralizing Omicron BA.2.86 and JN.1 subvariants than Omicron BA.1, BA.2, and XBB subvariants. Since the amino acid sequences of the S(1144–1156) are highly conserved among various SARS-CoV-2 variants, the immunogen containing the S(1144–1156) core epitope can be designed as a broadly effective COVID-19 vaccine. Key points: • Inoculation of mice with the S(1144–1156) peptide vaccine can induce bnAbs against various SARS-CoV-2 variants. • The S(1144–1156) peptide stimulated significant release of IFN-γ and IL-2 in vaccinated mouse splenocytes. • The S(1143–1157) and S(1142–1158) peptide vaccines can elicit more SARS-CoV-2 nAbs in mice. [ABSTRACT FROM AUTHOR]

Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions. Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds. Clinical Trial Registration ClinicalTrials.gov : NCT05590403. [ABSTRACT FROM AUTHOR]

There is an urgent need for vaccines against Neisseria gonorrhoeae , the causative agent of gonorrhea. Vaccination with an outer membrane vesicle–based Neisseria meningitidis vaccine provides some protection from N. gonorrhoeae ; however, the mechanisms underlying this cross-protection are unknown. To address this need, we developed multiplexed bead-based assays for the relative quantification of human and mouse IgG and IgA against N gonorrhoeae antigens. The assays were evaluated for analyte independence, dilutional linearity, specificity, sensitivity, intra- and interassay variability, and robustness to sample storage conditions. The assay was then used to test samples from mice and humans immunized with an N meningitidis outer membrane vesicle vaccine. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013–2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms—ophthalmologic and auditory—are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody. [ABSTRACT FROM AUTHOR]

Neutralising antibodies against the SARS-CoV-2 spike (S) protein are major determinants of protective immunity, though insufficient antibody responses may cause the emergence of escape mutants. We studied the humoral immune response causing intra-host evolution in a B-cell depleted, haemato-oncologic patient experiencing clinically severe, prolonged SARS-CoV-2 infection with a virus of lineage B.1.177.81. Following bamlanivimab treatment at an early stage of infection, the patient developed a bamlanivimab-resistant mutation, S:S494P. After five weeks of apparent genetic stability, the emergence of additional substitutions and deletions within the N-terminal domain (NTD) and the receptor binding domain (RBD) of S was observed. Notably, the composition and frequency of escape mutations changed in a short period with an unprecedented dynamic. The triple mutant S:Delta141-4 E484K S494P became dominant until virus elimination. Routine serology revealed no evidence of an antibody response in the patient. A detailed analysis of the variant-specific immune response by pseudotyped virus neutralisation test, surrogate virus neutralisation test, and immunoglobulin-capture enzyme immunoassay showed that the onset of an IgM-dominated antibody response coincided with the appearance of escape mutations. The formation of neutralising antibodies against S:Delta141-4 E484K S494P correlated with virus elimination. One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance. Author summary: In the immunocompromised host, prolonged infection and insufficient antibody responses favour the emergence of highly mutated SARS-CoV-2 variants. To better understand the selective pressure exerted by antiviral antibodies, we characterised the variant-specific humoral immune response and resulting intra-host evolution of SARS-CoV-2 in a B-lymphocyte-depleted patient experiencing severe infection. Treatment with a monoclonal antibody early in infection led to the selection and outgrowth of resistant virus. As their B-cell function recovered, the patient mounted an IgM-dominated antiviral antibody response, the onset of which closely correlated with the appearance of additional escape mutations within the spike protein. The strength and breadth of this antibody response gradually increased, resulting in the selection of a variant carrying several escape mutations within spike. The formation of neutralising antibodies against this variant resulted in virus elimination. Our study provides new insights into the selection process of viral escape mutants in immunocompromised patients. The resuming humoral immunity against SARS-CoV-2 can be dominated by IgM. This immune response is poorly detectable with routine diagnostic procedures yet may trigger and drive substantial viral intra-host evolution. Determination of antiviral antibody responses and correlating them with intra-host evolution may provide a better picture of the adaptability of currently circulating SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Centrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and cancer. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrosomes and can be engaged by the "mitotic surveillance" or the "PIDDosome pathway", respectively. Here, we show that early B cell progenitors frequently present extra centrioles, ensuing their high proliferative activity and related DNA damage. Extra centrioles are efficiently cleared during B cell maturation. In contrast, centriole loss upon Polo-like kinase 4 (Plk4) deletion causes apoptosis and arrests B cell development. This defect can be rescued by co-deletion of Usp28, a critical component of the mitotic surveillance pathway, that restores cell survival and maturation. Centriole-deficient mature B cells are proliferation competent and mount a humoral immune response. Our findings imply that progenitor B cells are intolerant to centriole loss but permissive to centriole amplification, a feature potentially facilitating their malignant transformation. Centrioles organize chromosome segregation, migration, and the immune synapse. Here, Schapfl et al. show that B cell progenitors tolerate centriole overamplification, but not loss, while mature B cells can mount a humoral immune response in their absence. [ABSTRACT FROM AUTHOR]

At the end of 2022, a huge tide of SARS‐CoV‐2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID‐19, yet profound analyses of Omicron variants‐induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS‐CoV‐2 was tested at three time points: 2–4, 8–10, and 14–16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non‐vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2–4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T‐cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8–10 weeks, half lost effective antibody protection at 14–16 weeks. However, most seronegative patients (76.2% at 2–4 weeks, 83.3% at 8–10 weeks) could develop effective T‐cell response. Notably, the inactivated wild‐type vaccinated patients exhibited weaker humoral and cellular immunity only at 2–4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute‐phase after infection is the major factor correlated with hospitalization. One‐month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14–16 weeks after infection for high‐risk MM population. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East‐Asian hospital‐based case–control study. We identified 16 IgG antibodies significantly elevated in EBV‐positive cHL compared with controls, defining an "East‐Asian antibody signature of EBV‐positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case–control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East‐Asian antibody signature of EBV‐positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV‐positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East‐Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East‐Asian population. This cross‐comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti‐EBV IgG antibodies (LMP‐1, TK, BALF2, BDLF3, and BBLF1), found in both population‐specific antibody signatures, represent a "core signature of EBV‐positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV‐positive cHL independent of population‐specific factors. [ABSTRACT FROM AUTHOR]

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre‐Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) specific antibodies including total antibodies, anti‐receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS‐CoV‐2 wild type (WT) and BA.4/5 variant. T cell responses against SARS‐CoV‐2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron‐infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long‐lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p <.05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p =.0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non‐reinfected patients (all p <.05), and those patients of unvaccinated at late stage receiving anti‐cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection. [ABSTRACT FROM AUTHOR]

Longitudinal humoral immune response to inactivated COVID-19 vaccines among people living with HIV (PLWH) have not yet been systematically investigated. We conducted a 6-month longitudinal study among vaccinated PLWH and HIV-Negative Controls (HNC) to determine whether the humoral immune response effects of the inactivated COVID-19 vaccine are different between the two groups of people. Totally, 46 PLWH and 38 HNC who received the inactivated COVID-19 vaccine on days 0 and 28 were enrolled. The SARS-CoV-2 neutralizing antibodies (nAbs) and total specific IgM and IgG antibodies were examined on Day 0-Day190. The level and positive seroconversion rate of nAbs peaked on Day 42 in HNC while peaked on Day 70 in PLWH, then decreased gradually with the extension of the vaccination period after the peaks. The peak level of nAbs in PLWH on Day 70, (GMC 8.07 BAU/mL, 95% CI 5.67-11.48) was significantly lower than in HNC on Day 42 (GMC 18.28 BAU/mL, 95% CI 10.33-32.33, P =0.03). The decrease in the geometric mean concentrations (GMCs) of nAbs was observed as 42.9% in PLWH after peak level, which decreased from 8.07 BAU/mL [95% CI: 5.67-11.48] on Day 70 to 4.61 BAU/mL [95% CI: 3.35-6.34] on Day 190 (p = 0.02). On Day 190, only seven (18%, [95% CI: 6-40]) HNC and five (11%, [95% CI: 4-25]) PLWH maintained positive nAbs response respectively. The geometric mean ELISA units (GMEUs) and positive seroconversion rate of IgG in PLWH dropped significantly from Day 70 (GMEUs, 0.20 EU/mL, [95% CI: 0.13-0.34]; seroconversion, 52%, [95% CI: 34-69]) to Day 190 (GMEUs, 0.05 EU/mL, [95% CI: 0.03-0.08], P<0.001; seroconversion, 18%, [95% CI: 8-33], P<0.001). There was no significant difference in levels and seroconversion rates of nAbs and IgG between the two groups on Day 190. The peak immunogenicity of the inactivated COVID-19 vaccine was delayed and inferior in PLWH compared to HNC, while no significant difference was found in six-month immunogenicity between the two groups. [ABSTRACT FROM AUTHOR]

The epidermal infiltration of neutrophils is a hallmark of psoriasis (PSO) and its activation leads to the release of neutrophil extracellular traps (NETs). However, the molecular mechanism of NETs-related genes (NETRGs) has not been extensively studied in PSO. To define NETs-related-biomarkers for PSO. The GSE13355 and GSE78097 datasets, and NETRGs gene set were included in this study. The datasets used in this study were all microarray data. The weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were used to mine key genes. Later on, single-gene gene set enrichment analysis (GSEA) and immune infiltration analysis were implemented. Finally, the expression of key genes was verified using quantitative real-time fluorescence PCR (qRT-PCR). A total of 3 key genes (S100A9, CLEC7A, and CXCR4) were derived, and they all had excellent diagnostic performance. The single-gene GSEA enrichment results indicated that the key genes were mainly enriched in the chemokine signaling pathway and humoral immune response in the high-expression group, while focal adhesion was enriched in the low-expression group. The correlation analysis indicated that all key genes were strongly negatively correlated with resting mast cells and TGF-β family member receptor, while they were strongly positively correlated with activated CD4 memory T cells and antigen processing and presentation. Lastly, the experimental results showed that the expression trends of key genes were consistent with public database. In this study, we successfully screened three potential PSO diagnostic genes (S100A9, CLEC7A and CXCR4) that were closely related to NETs, and these findings not only provided new molecular marker candidates for the precise diagnosis of PSO patients, but also revealed possible future therapeutic targets. However, further in-depth research and validation were necessary. [ABSTRACT FROM AUTHOR]

Background: Human adenoviruses (HAdVs) frequently cause common respiratory or gastrointestinal infections among children, adults, individuals with immune deficiencies, and other vulnerable populations with varying degree of symptoms, ranging from mild to server, and in some cases, even fatalities. Despite the significant clinical impact of HAdVs, there is currently no approved vaccine available. Methods: This study explores the potential of the adenovirus type 5 fiber knob (Ad5-FK) to stimulate the production of Ad-specific neutralizing antibodies and T-cell responses in mice. Based on structure predictions, we first expressed Ad5-FK in E. coli and confirmed the assembly of FK into its trimeric form. After testing the binding capability of the trimeric FK to susceptible cells, the immunogenicity of the protein in combination with the c-di-AMP adjuvant was assessed in BALB/c mice. Results: The purified Ad5-FK exhibited self-trimerization and maintained correct conformation akin to the authentic FK structure. This facilitated effective binding to susceptible HEK293 cells. Notably, the protein demonstrated significant inhibition of HEK293 cells infection by rAd5-GFP. Immunization of BALB/c mice with Ad5-FK, or Ad5-FK mixed with c-di-AMP yielded FK-specific antibodies with potent neutralization capacity. Significantly, Ad5-FK was found to elicit a vigorous CD4+ T-cell response in the immunized mice. Conclusion: Our findings underscore the efficacy of FK-based vaccine in eliciting anti-Ad humoral immune response and CD4 T-cell immune reactions essential for protection against viral infections. [ABSTRACT FROM AUTHOR]

Objective: To analyze the serum pertussis toxin immunoglobulin G (PT-IgG), IL-17 and IFN-y levels in children with pertussis, and their relationship with intestinal mucosal barrier function and humoral immunity. Methods: A total of 140 children with pertussis (pertussis group) who were admitted to the Department of Pediatrics at General Hospital of Ningxia Medical University from February 2020 to September 2023, and 80 children (control group) with 2 weeks or longer duration of persistent cough but without Bordetella pertussis were selected as the study subjects at the same time. Serum PT-IgG, interleukin-17 (IL-17) and interferon-gamma (IFN-y) levels in all subjects were measured by enzyme-linked immunosorbent assay. Intestinal mucosal barrier function [advanced glycation end products (AGEs), diamine oxidase (DAO) and endotoxin (ETX)] and humoral immunity [immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), complement C3 and complement C4] were evaluated. The correlation between the levels of PT-IgG, IL-17 and IFN-y and intestinal mucosal barrier function, humoral immunity in children with pertussis was analyzed. Results: Serum PT-IgG positive rate in the pertussis group was 35.00% (49/140). Serum IL-17, IFN-y, AGES, DAO, and ETX levels in the pertussis group were higher than those in the control group. Serum IgA, IgG, IgM, complement C3, and complement C4 levels in the pertussis group were lower than those in the control group (P<0.05). PT-IgG positive rate was negatively correlated with the levels of IL-17, IFN-y, AGEs and ETX in children with pertussis. PT-IgG positivity rate was positively correlated with the levels of IgA, IgM and complement C3. IL-17 and IFN-y were positively correlated with AGEs and ETX. IL-17 and IFN-y were negatively correlated with IgA and complement C3. IL-17 was positively correlated with IFN-y (P<0.05). Conclusion: Serum PT-IgG positive rate is low, while the levels of IL-17 and IFN-y are relatively high in children with pertussis. The three are related to intestinal mucosal barrier function and humoral immunity. Detecting these indicators can provide a basis for clinical decision-making. [ABSTRACT FROM AUTHOR]

Background and Objectives: The rapid spread of Newcastle disease (ND), driven by extensive commercial exchange in the poultry industry, necessitates urgent preventive measures. Although effective vaccines against the Newcastle disease virus (NDV) have been used since 1940, recent outbreaks and the limitations of current vaccines highlight the need for improved solutions. Advances in synthetic biology, reverse vaccinology, molecular biology, and recombinant DNA technology over the past 20 years have led to the development of recombinant vaccines, which offer enhanced protection and broader immunogenic coverage against NDV. This study aimed to express the immunogenic domains of Hemagglutinin Neuraminidase (HN) and Fusion (F) glycoproteins, linked to the heat-labile enterotoxin B subunit (LTB) bio-adjuvant, to develop an effective and reliable recombinant vaccine for NDV. Materials and Methods: In this study, the L(HN)2F protein, composed of the LTB bio-adjuvant and the immunogenic regions of the doubled Hemagglutinin Neuraminidase (HN-HN) and Fusion (F) epitope, was expressed in Escherichia coli. Subcutaneous injection was used to evaluate the humoral immune response in mice and the result was compared with B1 vaccine. Results: The induction of strong humoral immune responses proved the strong immunoreactivity of the recombinant protein. Conclusion: The IgG elicited by the recombinant proteins was comparable to that of the commercial B1 vaccine against NDV, indicating its potential as a viable candidate for further development and evaluation as a recombinant vaccine against NDV. [ABSTRACT FROM AUTHOR]

Introduction: Multidomain peptides (MDPs) are amino acid sequences that self-assemble to form supramolecular hydrogels under physiological conditions that have shown promise for a number of biomedical applications. K2(SL)6K2 ("K2"), a widely studied MDP, has demonstrated the ability to enhance the humoral immune response to co-delivered antigen. Herein, we sought to explore the in vitro and in vivo properties of a peptide with the same sequence but opposite chirality (D-K2) since peptides composed of D-amino acids are resistant to protease degradation and potentially more immunostimulatory than their canonical counterparts. Methods: K2 and D-K2 hydrogels were characterized and evaluated in vitro using circular dichroism, rheology, cryo-electron microscopy, and fluorescence recovery after photobleaching studies. In vivo experiments in SKH-1 mice were conducted to evaluate both ovalbumin release from the hydrogels and hydrogel degradation. The injection site of the hydrogels was analyzed using histology and humoral immunity was assessed by ELISA. Results: In vitro, the enantiomeric hydrogels exhibited similar rheological properties, and fluorescence recovery after photobleaching experiments demonstrated that the diffusion of ovalbumin (OVA), a model antigen, was similar within both hydrogels. In vivo, K2 and D-K2 peptide hydrogels had similar OVA release rates, both releasing 89% of the antigen within 8 days. Both hydrogels elicited a similar antigen-specific humoral immune response. However, the in vivo degradation of the D-K2 hydrogel progressed significantly slower than K2. After 4 weeks in vivo, only 23 ± 7% of the K2 hydrogel remained at the injection site compared to 94 ± 7% of the D-K2 hydrogel, likely due to their different protease susceptibilities. Conclusion: Taken together, these data suggest that peptide chirality can be a useful tool for increasing hydrogel residence time for biomedical applications that would benefit from long persistence times and that, if an antigen releases over a sufficiently short period, release can be largely independent of degradation rate, though slower-diffusing payloads may exhibit degradation rate dependence. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea and high mortality in neonatal piglets. Pseudorabies causes acute and often fatal infections in young piglets, respiratory disorders in growing pigs, and reproductive failure in sows. In late 2011, pseudorabies virus (PRV) variants occurred in Bartha-K61-vaccine-immunized swine herds, resulting in economic losses to the global pig industry. Therefore, it is essential to develop a safe and effective vaccine against both PEDV and PRV infections. In this study, we constructed a recombinant virus rPRV-PEDV S1 expressing the major neutralizing epitope region (COE, SS2, and SS6) of the PEDV S1 protein by homologous recombination technology and CRISPR/Cas9 gene editing technology, and then evaluated its biological characteristics in vitro and immunogenicity in pigs. The recombinant virus rPRV-PEDV S1 had similar growth kinetics in vitro to the parental rPRV NY-gE−/gI−/TK− strain, and was proven genetically stable in swine testicle (ST) cells and safe for piglets. PEDV S1-specific antibodies were detected in piglets immunized with rPRV-PEDV S1 on the 7th day post-immunization (dpi), and the antibody level increased rapidly at 14–21 dpi. Moreover, the immunized piglets receiving the recombinant virus exhibited alleviated clinical signs and reduced viral load compared to the unvaccinated group following a virulent PEDV HN2021 strain challenge. Also, piglets immunized with rPRV-PEDV S1 developed a PRV-specific humoral immune response and elicited complete protection against a lethal PRV NY challenge. These data indicate that the recombinant rPRV-PEDV S1 is a promising vaccine candidate strain for the prevention and control of PEDV and PRV infections. [ABSTRACT FROM AUTHOR]

Background: With the rapid advancement of optical image diagnostic technology, researchers are delving into the potential applications in the field of cancer diagnosis and treatment. The exact link between the SEZ6L2 gene and cancer immune infiltration remains elusive. Materials and Methods: This study aims to investigate the relationship between SEZ6L2 gene overexpression and cancer immune infiltration using optical image diagnostic technology, thereby presenting novel insights for enhancing cancer diagnosis and treatment strategies. Tissue samples obtained from cancer patients were meticulously analyzed to quantitatively assess the expression of the SEZ6L2 gene through light image diagnostic technology. Additionally, immunohistochemical techniques were employed to assess the nature and quantity of immune infiltrating cells within the cancerous tissues. Results: The enrichment pathways were found to include complement activation, circulating immunoglobulin mediated humoral immune response, protein activation cascade, immunoglobulin complex, and immunoglobulin. In addition, the expression of SEZ6L2 is closely related to the infiltration level of tumor infiltrating immune cells (TIICs), and there is a potential relationship between the expression of SEZ6L2 and different marker genes of TIIC. Conclusion: Increased SEZ6L2 mRNA expression in breast invasive carcinoma was significantly associated with negative prognosis and immune invasion. SEZ6L2 may be a novel prognostic biomarker and a potential immunotherapeutic target in BRCA. [ABSTRACT FROM AUTHOR]

Background: Among the Pentraxins, the long Pentraxin‐3 (PTX‐3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX‐3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C‐reactive protein (CRP), PTX‐3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta‐analysis comparing blood PTX‐3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics. Methods: We performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records. Results: Our synthesis revealed a statistically significant difference in PTX‐3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77–1.26, p <.001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL‐cholesterol and triglycerides concentrations. Conclusions: Our study has shown a significant increase in blood PTX‐3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX‐3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600). [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the accumulation of α‐synuclein (α‐syn) in the brain and progressive loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Although the role of neuroinflammation and cellular immunity in PD has been extensively studied, the involvement of humoral immunity mediated by antibodies and B cells has received less attention. This article provides a comprehensive review of the current understanding of humoral immunity in PD. Here, we discuss alterations in B cells in PD, including changes in their number and phenotype. Evidence mostly indicates a decrease in the quantity of B cells in PD, accompanied by a shift in the population from naïve to memory cells. Furthermore, the existence of autoantibodies that target several antigens in PD has been investigated (i.e., anti‐α‐syn autoantibodies, anti‐glial‐derived antigen antibodies, anti‐Tau antibodies, antineuromelanin antibodies, and antibodies against the renin‐angiotensin system). Several autoantibodies are generated in PD, which may either provide protection or have harmful effects on disease progression. Furthermore, we have reviewed studies focusing on the utilization of antibodies as a potential treatment for PD, both in animal and clinical trials. This review sheds light on the intricate interplay between antibodies and the pathological processes in PD, including complement system activation. Significance statement: Considering the well‐established involvement of the humoral immune system in the pathophysiology of Parkinson's disease, it is important to explore alterations in both the quantity and characteristics of B lymphocytes as the main humoral immune system cells in individuals with PD. Generally, B lymphocytes in this condition exhibit a decline in numbers and a tendency to adopt memory phenotype. Furthermore, the investigation of antibodies produced against various antigens, possessing either protective or detrimental effects may aid in enhancing our comprehension of the pathophysiological path of the disease. [ABSTRACT FROM AUTHOR]

Changes in the immune status and the content of blood transport components reflect adaptations in the human body in response to adverse factors, showcasing the organism's adaptive capabilities and functional state. In this study, we aimed to determine the features of the immune system and levels of transport components of the blood system in residents of the Arctic of the Russian Federation. Methods: The peripheral venous blood of 191 residents of the Arctic of the Russian Federation (Murmansk Oblast) aged 21–55 analyzed comprehensively. Blood was sampled from the ulnar vein on an empty stomach in the morning. The hemogram, phagocytic activity of neutrophils, lymphocyte content with CD3, CD4, CD8, CD10, CD19, CD16, CD71, CD25, HLA‐DR and CD95 phenotypes, concentrations of cytokines: TNF‐α, IFN‐γ, IL‐6, IL‐10, extracellular receptor pool: sCD71, sCD62L, sApo‐1/Fas, sFasL, circulating immune complexes (CIC) and blood transport components: haptoglobin (Hp), transferrin, IgM, IgG, IgA, IgE (immunoglobulins M, G, A and E) low‐density lipoproteins (LDL), and high density lipoprotein (HDL) were evaluated. The results were analyzed using descriptive statistics and comparative, factorial, and regression analyses. Results: Residents of the Murmansk Oblast exhibit a high prevalence of erythrocytosis (62.3%), thrombocytosis (25.0%), leukocytosis (20.1%), and increased hemoglobin (Hb) concentrations (42.5%), coupled with a significantly decreased level of active phagocytes (47.6%). A significantly decreased level of lymphocytes with phenotypes CD3 (92.4%), CD4 (40.4%), CD71 (62.3%) was revealed, coupled with the activation of lymphocytes with phenotypes CD16 (50.1%), CD8 (37.5%), CD19 (15.9%) and increased concentrations of pro‐inflammatory IFN‐γ (47.9%), IL‐6 (33.3%), and TNF‐α (20.1%). Elevated levels of sCD71 (56.6%), sCD62L (32.1%), sApo‐1/Fas (22.1%), sFasL (10.2%), and autoantibodies to double‐stranded DNA (57.1%), RNA (10.4%), and oLDL (oxidized‐modified LDL) (16.3%) were recorded in residents of the Murmansk Oblast. Arctic residents showed elevated concentrations of Hp (63.3%), IgM (63.9%), IgA (42.4%), IgE (18.8%), LDL (24.9%), and a decreased level of HDL (21.1%) owing to an ApoA‐I ligand deficiency (58.1%). Elevated levels of Hp in the blood are associated with increased erythrocyte aggregation frequency, T‐lymphocyte activation, and increased concentration of free receptors of the extracellular pool. Increased IgM and IgA levels in the blood are attributed to the need to bind components of the extracellular receptor pool sCD71, sCD62L, sApo‐1/Fas, sFasL and are associated with decreased levels lymphocyte with CD8 and CD16 phenotypes. The humoral immune response in Arctic residents is triggered when the cellular component of immunity is under strain which compounded by ineffective clearance of metabolic byproducts owing to imbalanced LDL and HDL lipid transport complexes. Conclusions: The immune system of Arctic residents is characterized by excessive cytotoxic activity of lymphocytes and increased concentrations of pro‐inflammatory cytokines, free forms of receptors of the extracellular pool, and autoantibodies. The change in the content of transport components of the blood system is directed at maintaining homeostasis by exhibiting antioxidant, anti‐inflammatory, and immunoregulatory properties. [ABSTRACT FROM AUTHOR]

Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross‐reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross‐reactive with serum from MVs immunized small mammals. These cross‐reactive epitopes were located in oligomerization perinuclear targeting and Daxx‐interacting domains. Most cross‐reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross‐reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE. [ABSTRACT FROM AUTHOR]

It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain‐mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low‐grade peripheral tumor‐induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll‐like receptor 2 agonist of Percoll‐enriched primary microglia cultures was comparable between tumor‐bearing and ‐free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)‐1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor‐induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype. [ABSTRACT FROM AUTHOR]

mRNA-based vaccines symbolize a new paradigm shift in personalized medicine for the treatment of infectious and non-infectious diseases. However, the reactogenicity associated with the currently approved formulations limits their applicability in autoinflammatory disorders, such as tumour therapeutics. In this study, we present a delivery system showing controlled immunogenicity and minimal non-specific inflammation, allowing for selective delivery of mRNA to antigen presenting cells (APCs) within the medullary region of the lymph nodes. Our platform offers precise control over the trafficking of nanoparticles within the lymph nodes by optimizing stealth and targeting properties, as well as the subsequent opsonization process. By targeting specific cells, we observed a potent adaptive and humoral immune response, which holds promise for preventive and therapeutic anti-tumoral vaccines. Through spatial programming of nanoparticle distribution, we can promote robust immunization, thus improving and expanding the utilization of mRNA vaccines. This innovative approach signifies a remarkable step forward in the field of targeted nanomedicine. [Display omitted] [ABSTRACT FROM AUTHOR]

Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy. We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS). At study termination with a median follow-up of 15.2 months (range 1.2–28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3–16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event. TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222 , https://clinicaltrials.gov/search?term=NCT02978222. • Patients with EOC were vaccinated with multiple antigenic folate receptor alpha (FRα) MHC class II peptides (TPIV200). • Immunization with TPIV200 was well-tolerated but did not increase progression-free survival or response rate. • While FRα is selectively expressed in EOC, timing of immunization or combination therapy may be needed to improve outcomes. [ABSTRACT FROM AUTHOR]

To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity. In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273). We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT). The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed. These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies. [ABSTRACT FROM AUTHOR]

Toll-like receptor (TLR) agonists, as promising adjuvants and immunotherapeutic agents, have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways. However, their clinical application is hindered by uncontrolled systemic inflammatory reactions. Therefore, it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy. In this study, we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes (1V209-Cho-Lip+) to mitigate undesired side effects. Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8+ T cells. The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip+ in tumor vaccines. Following immunization with 1V209-Cho-Lip++OVA, we observed a pronounced "depot effect" and enhanced trafficking to secondary lymphoid organs. Prophylactic vaccination with 1V209-Cho-Lip++OVA significantly delays tumor development, prolongs mouse survival, and establishes durable immunity against tumor recurrence. Additionally, 1V209-Cho-Lip++OVA, while used therapeutic tumor vaccine, has demonstrated its efficacy in inhibiting tumor progression, and when combined with anti-PD-1, it further enhances antitumor effects. Therefore, the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine. 1V209-Cho-Lip++OVA effectively co-delivers antigen and TLR7 agonist, thereby augmenting both humoral and cellular immunity to exert a superior anti-tumor effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Today, the use of enzymes to improve feed digestibility and achieve higher productivity has been considered as an effective strategy in the poultry industry. Phytase is an enzyme that is used in most commercial diets with the aim of breaking the bonds of phytic acid to increase the digestibility and absorption of nutrient. On the other hand, by carrying out breeding programs and subsequently reducing resistance to diseases due to the shift of nutrient for more production, more attention has been paid to immunity system and gut health. Therefore, gut health has a key role in the absorption of nutrient resulting from the activity of endogenous and endogenous enzymes. Hence, research in term of gut health modifiers such a prebiotics, probiotics, postbiotics, parabiotics and essential oils have increased. Among them, phytogenics have become more popular nowadays. Phytogenic supplements are known as their role on growth performance and increase profitability through improving microbiota balance and intestinal health. In addition to dietary phtoygenic supplemets, dietary calcium and phosphorus reduction is probablely effective tool led to phytase activity released nutrient. Results from studies have been showed that, slight decrease in the level of calcium and phosphorus is effective in increasing the efficiency of these mineral and gut health via reducing gut acidity. In the present study, effect of high amounts of phytase in combination with phytogenic additive in diets with reduced calcium and phosphorus on nutrient digestibility, humoral immunity and some related blood parameters of broiler chickens were investigated. Materials and Methods: The 672 one-day-old male broilers of Ross 308 strain were assigned to 12 dietary treatments and four replicats in a 2x2x3 factorial arrangement with different amounts of phytase (zero, 500 and 2000 FTU) and two levels of phytogenic supplement (zero and 200 mg/kg of feed) on two dietary calcium (normal=0.81, 0.72, 66%; reduced=0.71, 0.62 and 0.56% for different phases) and phosphorus (normal = 0.36, 0.32 and 0.29%; reduced=0.31, 0.27 and 0.24% for different phases) in a completely randomized design. Results and Discussion: Addition of phytase to the diets in combination to calcium and phosphorus reduction increased phosphorus digestibility compared to that normal diets (P<0.05). Increasing phytase from 0 to 500 and 2000 FTU increased digestibility of dry matter, organic matter, phosphorus, calcium and protein (P<0.05). The interaction effect of adding phytase enzyme along with decreasing the amount of calcium and phosphorus on the digestibility of calcium and phosphorus were significant (P<0.05), and the inclusion of phytogenic supplement at the levels of 500 and 2000 FTU of phytase per kg of feed increased phosphorus digestibility (P<0.05). Decreasing dietary calcium and phosphorus concentration and adding phytogenic additive, improved nutrient digestibility of nutrients except protein (P<0.05). Inclusion 2000 FTU of phytase in diets increased digestibility of nutrients and decreased blood calcium compared to the usual amount and diet without phytase (P<0.05). The blood concentratin of alanine aminotransferase reduced by 2000 FTU of phytase compared to 0 and 500 FTU (P<0.05). Dietary addition of phytase decreased alkaline phosphatase (P<0.05). High levels of phytase inceasded total serum immunoglobulins at the age of 28 and 41 days compared to the zero level (P<0.05), but there was no difference compared to the 500 FTU. Addition of phytase or phytogenic supplement improved antibody level against Newcastle at the age of 41 days (P<0.05). Conclusion: Based on the results of this research, 2000 FTU phytase compared to 500 FTU and adding phytogenic supplement had positive effects on nutrient digestibility, growth performance and immunity in broilers. [ABSTRACT FROM AUTHOR]