Systematic Review of Mucosal Immunity Induced by Oral and Inactivated Poliovirus Vaccines against Virus Shedding following Oral Poliovirus Challenge

Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5–30 days after a “challenge” dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08–0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59–1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82–1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV

Gendered Risk Perceptions Associated with Human-Wildlife Conflict: Implications for Participatory Conservation

This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities

Intranasal Immunization with an Archaeal Lipid Mucosal Vaccine Adjuvant and Delivery Formulation Protects against a Respiratory Pathogen Challenge

Archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) is a safe mucosal adjuvant that elicits long lasting and memory boostable mucosal and systemic immune responses to model antigens such as ovalbumin. In this study, we evaluated the potential of the AMVAD system for eliciting protective immunity against mucosal bacterial infections, using a mouse model of intranasal Francisella tularensis LVS (LVS) challenge. Intranasal immunization of mice with cell free extract of LVS (LVSCE) adjuvanted with the AMVAD system (LVSCE/AMVAD) induced F. tularensis-specific antibody responses in sera and bronchoalveolar lavage fluids, as well as antigen-specific splenocyte proliferation and IL-17 production. More importantly, the AMVAD vaccine partially protected the mice against a lethal intranasal challenge with LVS. Compared to LVSCE immunized and naïve mice, the LVSCE/AMVAD immunized mice showed substantial to significant reduction in pathogen burdens in the lungs and spleens, reduced serum and pulmonary levels of proinflammatory cytokines/chemokines, and longer mean time to death as well as significantly higher survival rates (p<0.05). These results suggest that the AMVAD system is a promising mucosal adjuvant and vaccine delivery technology, and should be explored further for its applications in combating mucosal infectious diseases

Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

<p>Abstract</p> <p>Background</p> <p>There have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs) in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa.</p> <p>Methods</p> <p>In FcγRIIB deficient (KO) and C57BL/6 (WT) mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA). Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c⁺MHC class II⁺cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c⁺APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs) <it>in vitro </it>were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs) differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL).</p> <p>Results</p> <p>In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c⁺MHC class II⁺cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c⁺APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously.</p> <p>Conclusion</p> <p>Antigen-specific IgG ameliorates allergic airway inflammation via FcγRIIB on DCs.</p

Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women

The Magnitude and Kinetics of the Mucosal HIV-Specific CD8+ T Lymphocyte Response and Virus RNA Load in Breast Milk

BACKGROUND: The risk of postnatal HIV transmission is associated with the magnitude of the milk virus load. While HIV-specific cellular immune responses control systemic virus load and are detectable in milk, the contribution of these responses to the control of virus load in milk is unknown. METHODS: We assessed the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+ T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian women throughout the period of lactation and correlated this response to milk virus RNA load and markers of breast inflammation. RESULTS: The magnitude and kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood and milk of the right and left breast, indicating independent regulation of these responses in each breast. However, there was no correlation between the magnitude of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load. Further, there was no correlation between the magnitude of this response and markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific CD8+ T lymphocyte response in milk does not appear to be solely determined by the milk virus RNA load and is likely only one of the factors contributing to maintenance of low virus load in milk

The B subunits of cholera and Escherichia coli heat-labile toxins enhance the immune responses in mice orally immunised with a recombinant live P-fimbrial vaccine for avian pathogenic E. coli

This study aimed to investigate the adjuvant effect of recombinant attenuated Salmonella expressing cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin B subunit (LTB) for the P-fimbriae subunit-based vaccine of avian pathogenic E. coli (APEC) in a murine model. The PapA-specific sIgA and IgG responses were significantly enhanced after immunisation with the Salmonella-PapA vaccine in the presence of CTB or LTB. The group immunised with the Salmonella-LTB strain promoted Th1-type immunity, whereas that immunised with the Salmonella-CTB strain produced Th2-type immunity. We concluded that both Salmonella-CTB and -LTB strains can enhance the immune response to PapA, and that the LTB strain may be a more effective adjuvant for APEC vaccination, which requires higher Th1-type immunity for protection. Thus, our findings provide evidence that immunisation with an adjuvant, LTB, is one of the strategies of developing effective vaccines against P-fimbriated APEC

Norms, Networks, Power, and Control: Understanding Informal Payments and Brokerage in Cross-Border Trade in Sierra Leone

Recent research has cast light on the variety of informal payments and practices that govern the day-to-day interactions between traders and customs agents at border posts in low-income countries. Building on this literature, this paper draws on survey and qualitative evidence in an effort to explore which groups are most advantaged and disadvantaged by the largely informal processes and norms governing cross-border trade. We find that understanding variation in strategies and outcomes across traders can only be effectively understood with reference to the importance of norms, networks, power, and the logic of control.Department for International DevelopmentBill and Melinda Gates Foundatio