Immune Interference Research Articles

Split-Type Electrochemical Immunoassay System Triggering Ascorbic Acid-Mediated Signal Magnification Based on a Controlled-Release Strategy.

This research put forward a novel split-type electrochemical (EC) immunosensor which integrated the controlled-release strategy with EC detection for application in the field of biosensing. Concretely, ascorbic acid (AA) was packaged in a cadmium sulfide (CdS)-capped spherical mesoporous bioactive glass (SBG) nanocarrier (SBGCdS) on account of encapsulation technology. To reduce the complexity of the bioanalysis, the detection antibody-labeled SBGCdS-AA bioconjugate was applied in a 96-well microplate for the immunoreaction process, which is independent of the EC determination procedure. Thus, the immune interference and steric hindrance caused by the accumulation of nanomaterials on the electrode could be minimized. Subsequently, AA was released efficiently via the destruction effect of dithiothreitol on the disulfide bond. In addition, for the as-prepared FcAI/l-Cys/gold nanoparticles (GNPs)/porous BiVO4 (p-BVO)/ITO EC sensing platform in the detection solution, the synergetic catalysis of Fc and GNPs/p-BVO toward the oxidation of the released AA could be realized, which triggered AA-mediated significant signal magnification throughout this study. In particular, p-BVO with an ordered nanoarray structure could accelerate the electron transfer to assist in sensitivity improvement of this system. This novel biosensor was capable of assaying the neuron-specific enolase (NSE) biomarker sensitively, from which a linear range of 0.001-100 ng/mL was derived along with a low detection limit of 1.08 pg/mL. An innovative way could be paved in the bioanalysis of NSE and other biomarkers.

Expression of recombinant 35 kDa fragment of VP2 protein of canine parvovirus using Escherichia coli expression system.

Background and Aim:Canine parvovirus (CPV) is one of the most common viral infections in dogs, causing acute hemorrhagic gastroenteritis and high mortality. Vaccination effectively prevents CPV infection. However, the currently available CPV vaccines have concerns such as maternal immunity interference, shedding of virus vaccine, and false-positive result based on polymerase chain reaction after vaccination. A subunit vaccine can overcome these problems. This study aimed to express the recombinant 35 kDa fragment of the VP2 protein (consisting of epitopes 1-7) and the recombinant full-length VP2 protein (consisting of epitopes 1-10) and to study the ability of these two recombinant proteins to react with rabbit anti-CPV polyclonal antibodies.Materials and Methods:The full length and 35 kDa fragment of VP2 gene of CPV were cloned into the pBAD202 Directional TOPO™ expression vector and expressed in E. coli. The recombinant full-length and the recombinant 35 kDa fragment proteins of VP2 were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting.Results:The recombinant full-length and the recombinant 35 kDa fragment VP2 genes were successfully cloned and expressed. The optimum concentrations of arabinose and induction time for the recombinant full-length and the recombinant 35 kDa fragment VP2 proteins were 0.2% for 6 h and 0.02% for 6 h, respectively. The recombinant full-length and the recombinant 35 kDa fragment VP2 protein molecular weights were approximately 81 and 51 kDa, respectively. The recombinant full-length and the recombinant 35 kDa fragment VP2 proteins specifically interacted with rabbit anti-CPV polyclonal antibodies.Conclusion:These results suggest that the recombinant 35 kDa fragment and the recombinant full-length VP2 proteins may be useful in developing a CPV diagnostic test or vaccine.

Altered immune cells in the liver and spleen of mice as a typical immune response to graphene oxide exposure

In this study, we comprehensively explored graphene oxide (GO)-induced systemic immune responses and interference with hematopoiesis in mice upon GO intravenous injection. In the liver and spleen, GO led to alterations in immune components at different time points. GO exposure showed an effect on the populations of different types of hepatic macrophages. In the liver, the populations of macrophages mainly affected by GO including Kupffer cells and monocyte-derived macrophages. Stimulated hepatic inflammation led to the infiltration of platelets from the circulation into the liver and decreased peripheral platelets population at day 1. Interestingly, a decreased platelet population was observed on day 7 in the spleen. GO also led to accelerated hematopoiesis in the spleen. Therefore, the possible forced generation of more platelets and the release of mature platelets from the spleen contributed to the increased circulating platelet count on day 7. Therefore, although GO showed a low potential to induce severe inflammation in the liver and spleen, it disrupted hematopoiesis in the spleen, which contributed to fluctuations in circulating platelet counts. The interaction of GO with the immune system warrants comprehensive study for gaining better understanding.

Overview of Immunological Responses and Immunomodulation Properties of Trichuris sp.: Prospects for Better Understanding Human Trichuriasis.

Trichuris sp. infection has appeared as a pathological burden in the population, but the immunomodulation features could result in an opportunity to discover novel treatments for diseases with prominent inflammatory responses. Regarding the immunological aspects, the innate immune responses against Trichuris sp. are also responsible for determining subsequent immune responses, including the activation of innate lymphoid cell type 2 (ILC2s), and encouraging the immune cell polarization of the resistant host phenotype. Nevertheless, this parasite can establish a supportive niche for worm survival and finally avoid host immune interference. Trichuris sp. could skew antigen recognition and immune cell activation and proliferation through the generation of specific substances, called excretory/secretory (ESPs) and soluble products (SPs), which mainly mediate its immunomodulation properties. Through this review, we elaborate and discuss innate–adaptive immune responses and immunomodulation aspects, as well as the clinical implications for managing inflammatory-based diseases, such as inflammatory bowel diseases, allergic, sepsis, and other autoimmune diseases.

Interactions between Biomedical Micro-/Nano-Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities.

Mobile micro- and nano-motors (MNMs) emerge as revolutionary platforms for biomedical applications, including drug delivery, biosensing, non-invasive surgery, and cancer therapy. While for applications in biomedical fields and practical clinical translation, the interactions of these untethered tiny machines with the immune system is an essential issue to be considered. This review highlights the recent approaches of surpassing immune barriers to prevent foreign motors from triggering immune responses. In addition to trials focusing on the function preservation of MNMs, examples of versatile MNMs working with the immune components (immune molecules, immune cells and the whole system) to achieve cancer immunotherapy, immunoassay, and detoxification are outlined. The immune interference part provides researchers an idea about what is the limit presented by the immune components. The coworking part suggests ways to bypass or even utilize the limit. With interdisciplinary cooperation of nanoengineering, materials science, and immunology field, the rationally designed functional MNMs are expected to provide novel opportunities for the biomedical field.

Oxidative Stress, Endocrine Disturbance, and Immune Interference in Humans Showed Relationships to Serum Bisphenol Concentrations in a Dense Industrial Area.

Bisphenol A (BPA) analogues, used in a range of products due to health concerns regarding BPA, have emerged as ubiquitous environmental contaminants worldwide. This study aims to evaluate the levels of nine bisphenols (BPs) and eight biomarkers (malondialdehyde, MDA; 8-hydroxy-2'-deoxyguanosine, 8-OHdG; estradiol, E2; follicle-stimulating hormone, FSH; luteinizing hormone, LH; complement compound 3, C3; immunoglobulin M, IgM and c-reaction protein, CRP) in human serum (n = 353) to explore their potential relationships. The detection rates (DRs) of eight BPs in serum samples taken from people working in a dense industrial area of Shenzhen (Guangdong Province, China) were over 72% except for bisphenol B (BPB) (DR = 27.5%). The mean concentrations of BPA, bisphenol P (BPP), BPB, bisphenol F (BPF), bisphenol FL (BPFL), 4,4'-dihydroxy-benzophenone (DHBP), bisphenol AF (BPAF), 4,4'-thiodiphenol (TDP) and bisphenol S (BPS) were 42.062, 2.083, 0.765, 0.578, 0.423, 0.402, 0.191, 0.120, and 0.071 ng/mL, respectively. BPA and BPFL were significantly correlated with the level of oxidative stress indices MDA and 8-OHdG; BPAF, BPB, and DHBP were strongly correlated with the level of endocrine disturbance indices E2, FSH, and LH; and BPF, DHBP, and BPAF were apparently related to the level of immune interference indices C3 and IgM. This study also suggests multiple impacts (oxidative stress, endocrine disturbance, and immune interference) mediated by BPs contaminants in vivo. To our knowledge, this is the first study to report the correlations among these nine serum BPs and oxidative stress and endocrine and immune system indices in human serum samples collected from dense industrial areas.

Obesity and high neutrophil-to-lymphocyte ratio are prognostic factors in non-metastatic breast cancer patients.

Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.

Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques.

The RV144 vaccine trial revealed a correlation between reduced risk of HIV infection and the level of nonneutralizing-antibody (Ab) responses targeting specific epitopes in the second variable domain (V2) of the HIV gp120 envelope (Env) protein, suggesting this region as a target for vaccine development. To favor induction of V2-specific Abs, we developed a vaccine regimen that included priming with DNA expressing an HIV V1V2 trimeric scaffold immunogen followed by booster immunizations with a combination of DNA and protein in rhesus macaques. Priming vaccination with DNA expressing the HIV recombinant subtype CRF01_AE V1V2 scaffold induced higher and broader V2-specific Ab responses than vaccination with DNA expressing CRF01_AE gp145 Env. Abs recognizing the V2 peptide that was reported as a critical target in RV144 developed only after the priming immunization with V1V2 DNA. The V2-specific Abs showed several nonneutralizing Fc-mediated functions, including ADCP and C1q binding. Importantly, robust V2-specific Abs were maintained upon boosting with gp145 DNA and gp120 protein coimmunization. In conclusion, priming with DNA expressing the trimeric V1V2 scaffold alters the hierarchy of humoral immune responses to V2 region epitopes, providing a method for more efficient induction and maintenance of V2-specific Env Abs associated with reduced risk of HIV infection.IMPORTANCE The aim of this work was to design and test a vaccine regimen focusing the immune response on targets associated with infection prevention. We demonstrated that priming with a DNA vaccine expressing only the HIV Env V1V2 region induces Ab responses targeting the critical region in V2 associated with protection. This work shows that V1V2 scaffold DNA priming immunization provides a method to focus immune responses to the desired target region, in the absence of immune interference by other epitopes. This induced immune responses with improved recognition of epitopes important for protective immunity, namely, V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.

Determinants of aflatoxin exposures in Kenyan School-aged children

ABSTRACT Aflatoxins are naturally occurring food toxins known to contaminate cereals with a carry-over effect in milk and meat products from farm animals raised on contaminated feed. In children, continuous consumption of aflatoxin-contaminated food is linked to immune suppression, vaccine interference and growth faltering while in adult populations, carcinogenesis in the liver has been established. We evaluate the main determinants of aflatoxin exposures among children recruited from primary schools in Makueni and Siaya Counties. A five-part questionnaire was administered to collect information from randomly selected participants. AflatoxinB1-lysine adducts in children’s sera and total aflatoxins in food samples were analyzed by High-Performance Liquid Chromatography with Fluorescence detection. Using Chi-squared tests and Kruskal–Wallis tests, children from low-income households had the highest aflatoxin exposure, p-value = 0.0029. Smaller family size, greater food diversity, and good farming practices were associated with low aflatoxin exposures p < 0.001. Individual households living under severe levels of poverty were evidently exposed to higher levels of aflatoxins.

Isolation and Histopathological Changes Associated with Non-Tuberculous Mycobacteria in Lymph Nodes Condemned at a Bovine Slaughterhouse.

Background: non-tuberculous mycobacteria (NTM) infect humans and animals and have a critical confounding effect on the diagnosis of bovine tuberculosis. The Official Mexican Standard (Norma Oficial Mexicana, NOM-ZOO-031-1995) for food safety regulates Mycobacterium bovis in cattle, but not the NTM species. The study’s objective was to isolate and identify the NTM present in condemned bovine lymph nodes in a slaughterhouse, characterize the histological lesions, and correlate bacteriological and microscopic findings with the antemortem tuberculin skin test. Methods: from 528 cattle, one or two pooled samples of lymph nodes from each animal were cultured for Mycobacteria spp. and processed for histopathology. Results: mycobacteria were isolated from 54/528 (10.2%) of the condemned lymph nodes; 25/54 (46.2%) of these isolates were NTM; 4 bacteriological cultures with fungal contamination were discarded. Granulomatous and pyogranulomatous inflammation were present in 6/21 (28.6%) and 7/21 (33.3%) of the NTM-positive lymph nodes, respectively. The species of NTM associated with granulomatous lymphadenitis were M. scrofulaceum, M. triviale, M. terrae, and M. szulgai, while those causing pyogranulomatous lesions were M. szulgai, M. kansasii, M. phlei, and M. scrofulaceum. Conclusions: the NTM infections can cause false-positive results in the tuberculin test because of cross immune reactivity and interference with the postmortem identification of M. bovis in cattle.

Laboratory development cellular immune features and immune interference of prototype escherichia coli and pseudomonas aeruginosa combined bacterins in a lapin model

Bacterial vaccines, the bacterins are of both prophylactic and therapeutic potentials .Autogenous bacterins

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)–recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs.MethodsNasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2.ResultsThe Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%).ConclusionsWinter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

Microneedles in Smart Drug Delivery.

Significance: In biomedical setup, at large, and drug delivery, in particular, transdermal patches, hypodermal needles, and/or dermatological creams with the topical appliance are among the most widely practiced routes for transdermal drug delivery. Owing to the stratum corneum layer of the skin, traditional drug delivery methods are inefficient, and the effect of the administered therapeutic cues is limited. Recent Advances: The current advancement at the microlevel and nanolevel has revolutionized the drug delivery sector. Particularly, various types of microneedles (MNs) are becoming popular for drug delivery applications because of safety, patient compliance, and smart action. Critical Issues: Herein, we reviewed state-of-the-art MNs as a smart and sophisticated drug delivery approach. Following a brief introduction, the drug delivery mechanism of MNs is discussed. Different types of MNs, that is, solid, hollow, coated, dissolving, and hydrogel forming, are discussed with suitable examples. The latter half of the work is focused on the applied perspective and clinical translation of MNs. Furthermore, a detailed overview of clinical applications and future perspectives is also included in this review. Future Directions: Regardless of ongoing technological and clinical advancement, the focus should be diverted to enhance the efficacy and strength of MNs. Besides, the possible immune response or interference should also be avoided for successful clinical translation of MNs as an efficient drug delivery system.

Cross talk between alcohol-induced oxidative stress and HCV replication.

Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and aggravates disease consequences in alcohol-abusing patients. Although the exact reasons by which alcohol consumption affects several cellular pathways in liver cells are not clear, they might be partially attributed to the ability of alcohol to further suppress the innate immunity, modulation of autophagy and also its relationship with reactive oxygen species (ROS) generation. To evaluate these issues, Huh7 cells harboring HCV replicon and Cytochrome p450 (CYP2E1) plasmid were exposed to ethanol and mRNA expression of Beclin-1, interferon-stimulated gene15 (ISG15) genesand HCV NS5B for two different times were relatively quantitated. ROS was determined by flow cytometry. The results showed that alcohol treatment in a short time caused an increase in HCV NS5B and Beclin-1 mRNA and decreased ISG 15 mRNA. Long-lasting alcohol treatment increased ROS production in Huh-7 cells and HCV replication was reduced. In conclusion, acute alcohol treatment might contribute to increase HCV replication by interference in innate immunity and induction of autophagy. Chronic alcohol treatment caused oxidative stress, which disrupts autophagy and thereby increased the rate of Huh7 cell injury.

The Effects of Pre-Existing Antibodies on Live-Attenuated Viral Vaccines.

Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal–fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus–antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcγRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy.

High-Density Wavelength Multiplexing Model for THz-EMI Transmission

We propose the use of the specific form of the integrated device known as the boxcar filters for big data transmission, where the advantage of such device is the number of roll-off (bandwidth) can be increased to meet the large demand of the future bandwidth requirements. A boxcar filter system is formed by the serial Panda-ring resonators, where the initial and end rings are used to form the whispering gallery mode beams for the light fidelity (LiFi) up-down-link conversion. There are 5 boxcar circuits within the system. Each of boxcar devices has the electro-optic connection that can be used to perform the external signal processing applications, where all electronic signals are changed to be the light signals and connected to the network via the free-space up-down link nodes. In a simulation, the selected light source is fed into the boxcar filters via the input port, in which the single roll-off bandwidth of 300 THz is obtained. The frequency guard band is given by each boxcar separation. In applications, the electromagnetic immunity interference (EMI) signals can be obtained by the electro-optic conversion circuit, which is the medical instrument specification requirement. The low EMI signals can be connected to the network and transmission using the LiFi network to the remote area. In addition, the medical information to home using the big data via the ad hoc LiFi network and the internet of thing platform arrangements are also proposed.

Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs

To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.

Alternative Vaccination Routes against Paratuberculosis Modulate Local Immune Response and Interference with Tuberculosis Diagnosis in Laboratory Animal Models.

Paratuberculosis (PTB) is an enteric granulomatous disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminants. Current vaccines have shown to be cost–effective control reagents, although they are restricted due to cross-interference with bovine tuberculosis (bTB). Therefore, novel vaccination strategies are needed and this study is focused on evaluating alternative vaccination routes and their effect on the local immune response. The MAP oral challenge rabbit model was used to evaluate and compare an experimental inactivated MAP vaccine through oral (VOR) and intradermal (VID) routes. The VID group presented the highest proportion of animals with no visible lesions and the lowest proportion of animals with MAP positive tissues. Immunohistochemistry analysis revealed that the VID group presented a dominantly M1 polarized response indicating an ability to control MAP infection. In general, all vaccinated groups showed lower calprotectin levels compared to the non-vaccinated challenged group suggesting less active granulomatous lesions. The VID group showed some degree of skin test reactivity, whereas the same vaccine through oral administration was completely negative. These data show that PTB vaccination has an effect on macrophage polarization and that the route influences infection outcome and can also have an impact on bTB diagnosis. Future evaluation of new immunological products against mycobacterial diseases should consider assaying different vaccination routes.

Metformin promotes susceptibility to experimental Leishmania braziliensis infection.

BACKGROUND Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET.OBJECTIVE To evaluate the modulatory effect of MET in Lb infection.MATERIAL AND METHODS Experimental study of Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages.FINDINGS MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages.MAIN CONCLUSION Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL.

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice.

The administration of antipyretic analgesics prior to, in conjunction with, or due to sequelae associated with vaccination is a common yet somewhat controversial practice. In the context of human vaccination, it is unclear if even short-term analgesic regimens can significantly alter the resulting immune response, as literature exists to support several scenarios including substantial immune interference. In this report, we used a live attenuated Yersinia pestis vaccine to examine the impact of analgesic administration on the immune response elicited by a single dose of a live bacterial vaccine in mice. Mice were assessed by evaluating natural and provoked behavior, as well as food and water consumption. The resulting immune responses were assessed by determining antibody titers against multiple antigens and assaying cellular responses in stimulated splenocytes collected from vaccinated animals. We observed no substantial benefit to the mice associated with the analgesic administration. Splenocytes from both C57BL/6 and BALB/c vaccinated mice receiving acetaminophen have a significantly reduced interferon-gamma (IFN-γ) recall response. Additionally, there is a significantly lower immunoglobulin (Ig)G2a/IgG1 ratio in vaccinated BALB/c mice treated with either acetaminophen or meloxicam and a significantly lower IgG2c/IgG1 ratio in vaccinated C57BL/6 mice treated with acetaminophen. Taken together, our data indicate that the use of analgesics, while possibly ethically warranted, may hinder the accurate characterization and evaluation of novel vaccine strategies with little to no appreciable benefits to the vaccinated mice.