Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response

Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4⁺ T cells in the lung. PA-specific CD4⁺ T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity.     

Durability of humoral immune responses to rubella following MMR vaccination

BackgroundWhile administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults.MethodsIn this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot.ResultsRubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women.ConclusionsCollectively, rubella-specific humoral immunity declines following vaccination, although subjects’ antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.     

Longitudinal analysis of the in vitro activity of ceftazidime-avibactam vs. Pseudomonas aeruginosa, 2012–2016

The in vitro activities of ceftazidime-avibactam and comparator agents were analyzed against 14,330 isolates of Pseudomonas aeruginosa from 188 centers distributed globally (except North America) from 2012 (2014 for colistin) to 2016 as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Susceptibility testing used in-house prepared broth microdilution panels following CLSI guidelines. Multiplex PCR assays identified the presence of β-lactamases. Ceftazidime-avibactam (MIC₉₀ 8 mg/L; 91.5% susceptibility) and colistin (N = 11,032; MIC₉₀ 2 mg/L, 96.2%) were the 2 most active agents. Susceptibility of multidrug-resistant isolates (N = 3770, 26.3%) was ≤54.4% to all agents except colistin (N = 2956; 95.2% susceptible) and ceftazidime-avibactam (68.2%). Metallo-β-lactamase–positive isolates (N = 621, 4.3%) were not susceptible to any agents except colistin (N = 504; 98.2% susceptible). Novel therapeutic options are needed for infections caused by P. aeruginosa–resistant phenotypes.     

Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15–20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy.     

Protective efficacy afforded by live Pasteurella multocida vaccines in chickens is independent of lipopolysaccharide outer core structure

Pasteurella multocida is a major animal pathogen that causes a range of diseases including fowl cholera. P. multocida infections result in considerable losses to layer and breeder flocks in poultry industries worldwide. Both killed whole-cell and live-attenuated vaccines are available; these vaccines vary in their protective efficacy, particularly against heterologous strains. Moreover, until recently there was no knowledge of P. multocida LPS genetics and structure to determine precisely how LPS structure affects the protective capacity of these vaccines. In this study we show that defined lipopolysaccharide (LPS) mutants presented as killed whole-cell vaccines elicited solid protective immunity only against P. multocida challenge strains expressing highly similar or identical LPS structures. This finding indicates that vaccination of commercial flocks with P. multocida killed cell formulations will not protect against strains producing an LPS structure different to that produced by strains included in the vaccine formulation. Conversely, protective immunity conferred by vaccination with live P. multocida strains was found to be largely independent of LPS structure. Birds vaccinated with a range of live mutants belonging to the L1 and L3 LPS genotypes, each expressing a specific truncated LPS structure, were protected against challenge with the parent strain. Moreover, birds vaccinated with any of the five LPS mutants belonging to the L1 LPS genotype were also protected against challenge with an unrelated strain and two of the five groups vaccinated with live LPS mutants belonging to the L3 genotype were protected against challenge with an unrelated strain. In summary, vaccination with live P. multocida aroA mutants producing full-length L1 or L3 LPS or vaccination with live strains producing shortened L1 LPS elicited strong protective immunity against both homologous and heterologous challenge.     

Effets d'un entraînement de type sprint sur les réponses catécholaminergiques à l'exercice bref et intense chez des adolescents

IntroductionThe purpose of this study was to evaluate the effect of sprint training on plasma catecholamine concentrations in response to a-6 second-sprint exercise in adolescent boys (GE). Moreover, to judge of the respective effects of training and pubertal maturation, we proposed the same protocol to a control group of adolescents (GT).ResultsHigher performances (P_max) were reported in GE after 6 months but did not change in CG. In response to sprint exercise, no change was found in maximal lactate concentrations (La_max) or in plasma noradrenaline concentrations (NA) in GE and GT. However, higher (A) responses were reported in GE and CG after the 6 seconds-sprint test and no difference was observed in this increase between the groups.ConclusionThese results suggest that in adolescent boys, sprint training may enhance performances but not catecholaminergic responses to short cycle ergometer sprinting.     

Investigations of a novel ferrocene-containing lipid by cyclic voltammetry and cryogenic transmission electron microscopy

A novel chiral redox-active ferrocene compound (FcVI) with amphiphilic properties has been synthesized. Cryogenic Transmission Electron Microscopy (cryo-TEM) has been used to estimate the shape and size of the FcVI aggregates in solution. Uni- and multi-lamellar vesicles (between 40 and 300 nm in diameter) were observed in water. Large particles (of more than 1 μm in diameter) with a hexagonal fine structure were found in 50 mM aqueous Na₂SO₄ solution. Sonication transformed the latter into ‘rosette’-like structures. Cyclic voltammetry has been employed to investigate the electrochemical properties of FcVI. The amphiphile adsorbed on graphite electrodes and a reversible electrochemical behaviour, characteristic of ferrocene, was observed with redox potentials between 330 and 350 mV.