Macleaya cordata extract exhibits some potential as a surrogate antibiotic by improving gastrointestinal epithelial status and humoral response in goats.

Macleaya cordata extract (MCE) is a potential replacement for antibiotics. In the current study, effects of MCE on the gastrointestinal health and humoral responses of host animals were explored. A total of 30 weanling goats with similar body weight of 9.15 ± 1.36 kg were randomly allocated into three groups (n = 10 per group): control group (CON group, fed with a basal diet), antibiotic group (Abx group, fed with the basal diet supplemented with 0.18 g/d vancomycin and 0.36 g/d neomycin), and MCE group (fed with the basal diet supplemented with 5 g/d MCE), for three weeks. Results showed that antibiotic addition decreased the height and area of rumen papillae, ruminal mucosa Toll-like receptor 8 (TLR8), interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) gene relative expression levels and microbial diversity, altered the volatile fatty acid (VFA) profile in the rumen, and increased monocytes amount and CD4+ T cells percentage in the peripheral blood (P < 0.05) compared to CON group. MCE addition increased the average daily gain, ileal villus height, villus height/crypt depth, and immunoglobulin M (IgM) content in the peripheral blood (P < 0.05) compared to the CON. Additionally, MCE addition decreased the proportion of isobutyric acid in the chyme of the ileum (P = 0.005) compared to the CON group. These results suggest that antibiotic supplementation may suppress the epithelial state and microbial diversity and fermentation in goats, but stimulate cellular response to maintain the growth performance of goats. MCE administration improved the epithelial state and humoral response to promote the growth performance in goats.

Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients-a longitudinal cohort study.

Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection. Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests. Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response. Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.

Assessment of the humoral immune status of varicella-zoster virus in patients with diffuse connective tissue diseases.

Background: Diffuse connective tissue diseases (DCTDs) require long-term immunosuppressive treatment, increasing the risk of varicella-zoster virus (VZV) infection. This study aims to evaluate the humoral immune status against VZV in DCTD patients and explore factors that may influence their immune levels. Methods: This is a retrospective cohort study that collected data from adult DCTD patients (≥18 years) attending our outpatient clinic. The geometric mean concentration (GMC) of VZV-specific IgG antibodies in the patients' sera was measured using the enzyme-linked immunosorbent assay (ELISA). Results: A total of 280 RA patients, 272 SLE + MCTD patients and 280 healthy controls were included. SLE + MCTD patients had significantly higher VZV IgG antibody levels than RA patients (p < 0.05) but showed no significant difference compared to healthy controls (p > 0.05). Notable differences were observed particularly among female patients and those aged 30-49 years, (p < 0.05). SLE + MCTD patients in an active disease state had significantly higher VZV IgG antibody titers than RA patients (p < 0.05). Additionally, patients with a history of herpes zoster, regardless of being in the SLE + MCTD, RA, or control group, exhibited higher VZV IgG titers (p < 0.05). Conclusion: Although DCTD patients, particularly those with SLE and MCTD, exhibit higher VZV IgG antibody levels, they still face a higher risk of developing herpes zoster (HZ), which may be related to their underlying disease and immunosuppressive treatment. The presence of antibodies alone may not provide complete protection, necessitating consideration of cellular immune mechanisms. It is recommended to enhance monitoring of VZV antibody levels in high-risk patients and consider herpes zoster vaccination to reduce HZ-related complications.

Immunomodulation and Humoral Immune Response in Teleost Immunized with Aeromonas-Derived Antigenic Extracellular Bioactive Molecules.

The common use of antimicrobials in food-animal production can lead to drug residues in edible tissues for consumers. However, immunomodulators enhance immune responses and vaccine effectiveness. A new perspective explores bacterial extracellular bioactive molecules (EBMs) in food-animal production to modulate host immune responses, potentially transforming pathogen management and antimicrobial use. This study investigates the immunogenic potential of Aeromonas hydrophila-derived EBMs (Antigens) to enhance the immune system. Four Antigens were administered intraperitoneally to Oreochromis niloticus (Nile Tilapia). Antigens 2 and Antigens 3 boosted fish immune competence within 21 days. Remarkably, Antigens 3 induced robust immunity against A. hydrophila with a single dose, notably enhancing antibody-based immune responses. The increased antibody activity suggests Antigens 3 could be a vaccine candidate, promising further research and potential application in food-animal production to improve disease control. This study highlights immunomodulators' potential in reshaping disease management in the food-animal industry, emphasizing the benefits of focusing on bacterial EBMs to reduce reliance on antimicrobials and achieve sustainable disease prevention.

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

Kinetics of humoral and cellular immune responses 5 months post-COVID-19 booster dose by immune response groups at the peak immunity phase: An observational historical cohort study using the Fukushima vaccination community survey.

Background: Understanding the waning of immunity after booster vaccinations is important to identify which immune-low populations should be prioritized. Methods: We investigated longitudinal cellular and humoral immunity after the third vaccine dose in both high- and low-cellular and humoral immunity groups at the peak immunity phase after the booster vaccination in a large community-based cohort. Blood samples were collected from 1045 participants at peak (T1: median 54 days post-third dose) and decay (T2: median 145 days post-third dose) phases to assess IgG(S), neutralizing activity, and ELISpot responses. Participants were categorized into high/low ELISpot/IgG(S) groups at T1. Cellular and humoral responses were tracked for approximately five months after the third vaccination. Results: In total, 983 participants were included in the cohort. IgG(S) geometric mean fold change between timepoints revealed greater waning in the >79 years age group (T2/T1 fold change: 0.27) and higher IgG(S) fold change in the low-ELISpot group at T1 (T2/T1 fold change: 0.32-0.33) than in the other groups, although ELISpot geometric mean remained stable. Conclusions: Antibody level of those who did not respond well to third dose vaccination waned rapidly than those who responded well. Evidence-based vaccine strategies are essential in preventing potential health issues caused by vaccines, including side-effects.

Pentachlorophenol impairs the antimicrobic capability of blood clam via undermining humoral immunity and disrupting humoral-cellular crosstalk.

Due to past massive usage and persistent nature, pentachlorophenol (PCP) residues are prevalent in environments, posing a potential threat to various organisms such as sessile filter-feeding bivalves. Although humoral immunity and its crosstalk with cellular one are crucial for the maintaining of robust antimicrobic capability, little is known about the impacts of PCP on these critical processes in bivalve mollusks. In this study, pathogenic bacterial challenge and plasma antimicrobic capability assays were carried out to assess the toxic effects of PCP on the immunity of a common bivalve species, blood clam (Tegillarca granosa). Moreover, the impacts of PCP-exposure on the capabilities of pathogen recognition, hemocyte recruitment, and pathogen degradation were analyzed as well. Furthermore, the activation status of downstream immune-related signalling pathways upon PCP exposure was also assessed. Data obtained illustrated that 28-day treatment with environmentally realistic levels of PCP resulted in evident declines in the survival rates of blood clam upon Vibrio challenge along with markedly weakened plasma antimicrobic capability. Additionally, the levels of lectin and peptidoglycan-recognition proteins (PGRPs) in plasma as well as the expression of pattern recognition receptors (PRRs) in hemocytes were found to be significantly inhibited by PCP-exposure. Moreover, along with the downregulation of immune-related signalling pathway, markedly fewer chemokines (interleukin 8 (IL-8), IL-17, and tumor necrosis factor α (TNF-α)) in plasma and significantly suppressed chemotactic activity of hemocytes were also observed in PCP-exposed blood clams. Furthermore, compared to that of the control, blood clams treated with PCP had markedly lower levels of antimicrobic active substances, lysozyme (LZM) and antimicrobial peptides (AMP), in their plasma. In general, the results of this study suggest that PCP exposure could significantly impair the antimicrobic capability of blood clam via undermining humoral immunity and disrupting humoral-cellular crosstalk.

Humoral Immunity and Antibody Responses against Diphtheria, Tetanus, and Pneumococcus after Immune Effector Cell Therapies: A Prospective Study.

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3-6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3-6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3-6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3-6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed.

Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice.

Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.

Candida, a fungus, is a major cause of bloodstream infections, especially in critical care settings. This study focused on developing a vaccine to protect against Candida infection. The vaccine targeted two key proteins, Als3p and Hyr1p, found on the surface of Candida, using a combination of these proteins. To create the vaccine, we used Als3p and Hyr1p to form a fusion protein called AH, and tested the vaccine on mice, administering it with different adjuvants (substances that enhance the immune response). The results showed that the AH vaccine, particularly when combined with the adjuvant AlPO₄, induced a strong immune response in mice. This response included the production of specific antibodies and immune cells that are crucial for defending against Candida infections. Furthermore, mice receiving the AH-AlPO₄ vaccine showed significantly better survival rates and lower levels of fungal infection compared to the control group or another experimental group. The vaccine also protected vital organs, such as the kidneys and liver, from Candida-induced damage. Additionally, we used rabbit serum to validate the efficacy of the vaccine, providing cross-species confirmation of its effectiveness. The study demonstrated the potential of the AH vaccine in eliciting robust immune responses and reducing the severity of Candida albicans infections. In summary, this research introduces a promising AH vaccine, which shows effectiveness in protecting against Candida infections. The study's innovative approach and positive results contribute to the ongoing efforts to develop vaccines against fungal infections, addressing a critical healthcare challenge. Further research is needed to explore the vaccine's long-term effectiveness and safety for potential use in clinical settings.

Production of recombinant cytokines and polyclonal antibodies for analysis of cellular immune response in golden Syrian hamster.

BACKGROUND: The development of therapies and vaccines for various diseases often necessitates the analysis of cellular immunity. However, unlike other rodents, the limited availability of reagents for Syrian hamsters restricts immunological analysis, particularly in the determination of serum effector molecules such as cytokines. In this study, we aim to produce and characterize the cytokines IFN-γ, TGF-ß, IL-6, IL-10, and TNF-α from Syrian hamsters in recombinant form and to generate polyclonal antibodies against them in rats. METHODS AND RESULTS: Cytokine transcript sequences were cloned into expression vectors in E. coli. Recombinant proteins were produced, purified through affinity chromatography, and characterized by Western blot using an anti-6xHis monoclonal antibody. Rats were immunized with the recombinant proteins to generate polyclonal antibodies (pAbs). These pAbs were characterized by Western blot and titrated by indirect ELISA. The recombinant cytokines rTNF-α, rIL-10, rIFN-γ, rTGF-ß, and rIL-6 were produced and specifically recognized at their expected molecular weights of 22.3 kDa, 19.8 kDa, 18.9 kDa, 11.8 kDa, and 22.9 kDa. pAbs were produced and demonstrated the ability to specifically recognize their target proteins with titers of 409,600 (rIL-10), 204,800 (rTNF-α), 102,400 (rIL-10), 51,200 (rTGF-ß), and 25,600 (rIFN-É£). CONCLUSIONS: The reagents produced represent a starting point for developing immunoassays to detect hamster cytokines, facilitating the analysis of cellular immunity in this biomodel.

How does adulteration of wax foundation affect phenoloxidase and lysozyme activities as selected parameters of immunity in Apis mellifera?

Introduction: The adulteration of wax foundation is, for many reasons, a growing problem of modern beekeeping not only in Europe but also around the world. Wax foundation contaminated with stearin addition leads to a brood die-off, while paraffin addition negatively affects the strength of combs. It is tenable that such adulterated wax foundation reduces bees' immunity. The aim of the study was to determine the activities of two bee immune enzymes, lysozyme and phenoloxidase, in the haemolymph of worker bees which had emerged from combs with wax foundations contaminated with stearin or paraffin. Material and Methods: Combs built with stearin- or paraffin-adulterated wax (both adulterants at concentrations of 10%, 30% or 50%) or pure wax (0% adulterated) foundations were placed in the colonies, one for each adulterant and percentage. The workers were marked upon emergence from these combs and those bees were introduced into one strong colony per adulterant and percentage. Phenoloxidase and lysozyme activities were determined in the haemolymph of 1-, 7- and 14-day-old workers. Results: The higher the concentrations of stearin and paraffin in the wax foundation, the lower the phenoloxidase activities were. These activities increased with the bee age. In contrast, the trends in lysozymes were opposite. Paraffin seems to be less toxic than stearin. Conclusion: Adulteration of wax foundation with even a small amount of stearin or paraffin has negative effects on the functioning of the bee.

Analysis of the role of Dirofilaria repens macrophage migration inhibitory factors in host-parasite interactions.

Introduction: Dirofilaria repens is a zoonotic parasitic filarial nematode that infects carnivores and occasionally humans. Knowledge of the host-parasite molecular interactions enabling the parasite's avoidance of the host immune response in subcutaneous dirofilariasis remains limited. Parasitic orthologues of host macrophage migration inhibitory factor (MIF) are molecules potentially involved in this process. Material and Methods: Complementary DNA encoding two D. repens MIF orthologues (rDre-MIF-1 and rDre-MIF-2) was cloned into a pET-28a expression vector. The recombinant proteins were produced in Escherichia coli and purified using affinity nickel chromatography. The reactivity of both recombinant proteins was analysed with infected dog and immunised mouse sera. Results: Stronger antibody production was induced by rDre-MIF-1 in mice, as evidenced by significantly higher levels of anti-rDre-MIF-1 total IgG, IgG2 and IgE antibodies than of anti-rDre-MIF-2 immunoglobulins. Additionally, a significantly different level of antibodies specific to both proteins was noted between the sera of infected dogs and those of uninfected dogs. Conclusion: This study is the first attempt to characterise MIF orthologues from the filarial parasite D. repens, which may affect the immune response during infection.

Antibody Isotype and Subclass Responses in Human Patients With Different Clinical Presentations of Sporotrichosis.

Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition.

Transitions of Care in Patients With Inborn Errors of Immunity.

Inborn errors of immunity (IEI) are a group of inherited conditions caused by damaged monogenic variants that result in impairment and/or dysregulation within the immune system. IEI are typically diagnosed in infancy or early childhood, with clinical presentations that include increased susceptibility to infections, immune dysregulation, autoinflammation, bone marrow failure, and/or malignancy. Historically, transitions of care experienced by patients with IEI have not been well described in the literature. However, with treatment advances extending the long-term survival of patients, this has become a primary area of research. It is crucial to establish guidelines and recommendations specific to the transition of patients with IEI. Transitions may include patients who naturally progress from pediatric to adult care, from inpatient to outpatient settings, or from their established health care team to a new team (ie, moving from one geographic area to another). This narrative review summarizes the current data on transitions of care and describes the health care challenges and patient-related barriers impacting transitions of care. Frameworks with practical guidance on how health care practitioners can better manage care transitions faced by patients with IEI are presented.

Vaccine-induced humoral response of BNT162b2 and mRNA-1273 against BA.1, BA.5, and XBB.1.5. (sub)variants 6 months after a homologous booster: is immunogenicity equivalent?

Introduction: Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable. Material and methods: Blood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant. Results: Once the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48). Conclusion: Although the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

Enhanced immune response with baculovirus-expressed BoHV-1 glycoprotein D in vaccine development.

Bovine herpesvirus 1 (BoHV-1), a significant pathogen in the alpha-herpesvirus subfamily, primarily infects cattle and causes the upper respiratory disease known as infectious bovine rhinotracheitis (IBR). In silico studies evaluated the BoHV-1 D protein to be non-allergenic, non-toxic, and highly antigenic, highlighting its potential as an antigen for vaccine development. Therefore, this study aimed to evaluate the efficacy of a subunit vaccine using the ectodomain of glycoprotein D (gD34-380) as an antigen. The truncated gD was successfully cloned and expressed in both Escherichia coli (E. coli, termed EgD) and baculovirus (termed BgD) systems, with expected molecular weights of 65 kDa and 50 kDa, respectively. For the vaccine formulation, the gD proteins were used either alone or in combination with in-house inactivated BoHV-1. Vaccination of mice and bovines showed that baculovirus-expressed gD34-380 accelerated the antibody response. Moreover, the BgD-vaccinated group also showed significantly higher neutralizing antibody levels against BoHV-1 than the control group (p<0.0001). In conclusion, our study found that BgD from BoHV-1 can increase the immune response and enhance vaccine efficacy.

SARS-CoV-2 Infection Enhances Humoral Immune Response in Vaccinated Liver Transplant Recipients.

In the spring of 2020, the SARS-CoV-2 pandemic presented a formidable challenge to national and global healthcare systems. Immunocompromised individuals or those with relevant pre-existing conditions were particularly at risk of severe coronavirus disease 2019 (COVID-19). Thus, understanding the immunological processes in these patient groups is crucial for current research. This study aimed to investigate humoral immunity following vaccination and infection in liver transplant recipients. Humoral immunity analysis involved measuring IgG against the SARS-CoV-2 spike protein (anti-S IgG) and employing a surrogate virus neutralization test (sVNT) for assessing the hACE2 receptor-binding inhibitory capacity of antibodies. The study revealed that humoral immunity post-vaccination is well established, with positive results for anti-S IgG in 92.9% of the total study cohort. Vaccinated and SARS-CoV-2-infected patients exhibited significantly higher anti-S IgG levels compared to vaccinated, non-infected patients (18,590 AU/mL vs. 2320 AU/mL, p < 0.001). Additionally, a significantly elevated receptor-binding inhibitory capacity was observed in the cPassTMTM sVNT (96.4% vs. 91.8%, p = 0.004). Furthermore, a substantial enhancement of anti-S IgG levels (p = 0.034) and receptor-binding inhibition capacity (p < 0.001) was observed with an increasing interval post-transplantation (up to 30 years), calculated by generalized linear model analysis. In summary, fully vaccinated liver transplant recipients exhibit robust humoral immunity against SARS-CoV-2, which significantly intensifies following infection and with increasing time after transplantation. These findings should be considered for booster vaccination schemes for liver transplant recipients.

Prevalence of Influenza B/Yamagata Viruses From Season 2012/2013 to 2021/2022 in Italy as an Indication of a Potential Lineage Extinction.

BACKGROUND: Influenza B/Yamagata viruses exhibited weak antigenic selection in recent years, reducing their prevalence over time and requiring no update of the vaccine component since 2015. To date, no B/Yamagata viruses have been isolated or sequenced since March 2020. METHODS: The antibody prevalence against the current B/Yamagata vaccine strain in Italy was investigated: For each influenza season from 2012/2013 to 2021/2022, 100 human serum samples were tested by haemagglutination inhibition (HAI) assay against the vaccine strain B/Phuket/3073/2013. In addition, the sequences of 156 B/Yamagata strains isolated during the influenza surveillance activities were selected for analysis of the haemagglutinin genome segment. RESULTS: About 61.9% of the human samples showed HAI antibodies, and 21.7% had protective antibody levels. The prevalence of antibodies at protective levels in the seasons between the isolation of the strain and its inclusion in the vaccine was between 11% and 25%, with no significant changes observed in subsequent years. A significant increase was observed in the 2020/2021 season, in line with the increase in influenza vaccine uptake during the pandemic. Sequence analysis showed that from 2014/2015 season onward, all B/Yamagata strains circulating in Italy were closely related to the B/Phuket/2013 vaccine strain, showing only limited amino acid variation. CONCLUSIONS: A consistent prevalence of antibodies to the current B/Yamagata vaccine strain in the general population was observed. The prolonged use of a well-matched influenza vaccine and a low antigenic diversity of B/Yamagata viruses may have facilitated a strong reduction in B/Yamagata circulation, potentially contributing to the disappearance of this lineage.

Evaluation of comparative effect between aluminum hydroxide gel and montanide (ISA 70) in potency and protection of locally prepared rabbit hemorrhagic disease virus 2 (RHDV2) vaccines in rabbits.

BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.