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Vaccines, Volume 5, Issue 3 (September 2017)

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Research

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Open AccessArticle The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection
Vaccines 2017, 5(3), 16; doi:10.3390/vaccines5030016
Received: 30 March 2017 / Revised: 23 June 2017 / Accepted: 28 June 2017 / Published: 3 July 2017
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Abstract
Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic.
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Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting. Full article
(This article belongs to the Special Issue Host Responses to Viral Infection)
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Open AccessArticle Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population
Vaccines 2017, 5(3), 17; doi:10.3390/vaccines5030017
Received: 30 May 2017 / Revised: 6 July 2017 / Accepted: 7 July 2017 / Published: 17 July 2017
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Abstract
Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and
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Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad response of heterotypic antibodies against avian influenza viruses, albeit at a low level. Full article
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Open AccessArticle Adjuvantation of Pulmonary-Administered Influenza Vaccine with GPI-0100 Primarily Stimulates Antibody Production and Memory B Cell Proliferation
Vaccines 2017, 5(3), 19; doi:10.3390/vaccines5030019
Received: 12 April 2017 / Revised: 19 June 2017 / Accepted: 21 July 2017 / Published: 27 July 2017
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Abstract
Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and
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Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and whole inactivated influenza virus (WIV) vaccine administered via the pulmonary route. However, the impact of the GPI-0100 dose on immune stimulation and the immune mechanisms stimulated by GPI-0100 along with antigen are poorly understood. Therefore, in this study we immunized C57BL/6 mice via the pulmonary route with vaccine consisting of WIV combined with increasing amounts of GPI-0100, formulated as a dry powder. Adjuvantation of WIV enhanced influenza-specific mucosal and systemic immune responses, with intermediate doses of 5 and 7.5 μg GPI-0100 being most effective. The predominant antibody subtype induced by GPI-0100-adjuvanted vaccine was IgG1. Compared to non-adjuvanted vaccine, GPI-0100-adjuvanted WIV vaccine gave rise to higher numbers of antigen-specific IgA- but not IgG-producing B cells in the lungs along with better mucosal and systemic memory B cell responses. The GPI-0100 dose was negatively correlated with the number of influenza-specific IFNγ- and IL17-producing T cells and positively correlated with the number of IL4-producing T cells observed after immunization and challenge. Overall, our results show that adjuvantation of pulmonary-delivered WIV with GPI-0100 mostly affects B cell responses and effectively induces B cell memory. Full article
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Open AccessArticle Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
Vaccines 2017, 5(3), 21; doi:10.3390/vaccines5030021
Received: 3 May 2017 / Revised: 29 July 2017 / Accepted: 2 August 2017 / Published: 9 August 2017
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Abstract
Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system
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Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans. Full article
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Open AccessFeature PaperArticle Challenges in Estimating Vaccine Coverage in Refugee and Displaced Populations: Results From Household Surveys in Jordan and Lebanon
Vaccines 2017, 5(3), 22; doi:10.3390/vaccines5030022
Received: 2 June 2017 / Revised: 19 July 2017 / Accepted: 31 July 2017 / Published: 12 August 2017
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Abstract
Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and
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Ensuring the sustained immunization of displaced persons is a key objective in humanitarian emergencies. Typically, humanitarian actors measure coverage of single vaccines following an immunization campaign; few measure routine coverage of all vaccines. We undertook household surveys of Syrian refugees in Jordan and Lebanon, outside of camps, using a mix of random and respondent-driven sampling, to measure coverage of all vaccinations included in the host country’s vaccine schedule. We analyzed the results with a critical eye to data limitations and implications for similar studies. Among households with a child aged 12–23 months, 55.1% of respondents in Jordan and 46.6% in Lebanon were able to produce the child’s EPI card. Only 24.5% of Syrian refugee children in Jordan and 12.5% in Lebanon were fully immunized through routine vaccination services (having received from non-campaign sources: measles, polio 1–3, and DPT 1–3 in Jordan and Lebanon, and BCG in Jordan). Respondents in Jordan (33.5%) and Lebanon (40.1%) reported difficulties obtaining child vaccinations. Our estimated immunization rates were lower than expected and raise serious concerns about gaps in vaccine coverage among Syrian refugees. Although our estimates likely under-represent true coverage, given the additional benefit of campaigns (not captured in our surveys), there is a clear need to increase awareness, accessibility, and uptake of immunization services. Current methods to measure vaccine coverage in refugee and displaced populations have limitations. To better understand health needs in such groups, we need research on: validity of recall methods, links between campaigns and routine immunization programs, and improved sampling of hard-to-reach populations. Full article
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Review

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Open AccessReview Egg-Independent Influenza Vaccines and Vaccine Candidates
Vaccines 2017, 5(3), 18; doi:10.3390/vaccines5030018
Received: 8 June 2017 / Revised: 4 July 2017 / Accepted: 6 July 2017 / Published: 18 July 2017
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Abstract
Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a
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Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines. Full article
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Open AccessReview Maternal Immunization: New Perspectives on Its Application Against Non-Infectious Related Diseases in Newborns
Vaccines 2017, 5(3), 20; doi:10.3390/vaccines5030020
Received: 9 May 2017 / Revised: 24 July 2017 / Accepted: 26 July 2017 / Published: 1 August 2017
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Abstract
The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection
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The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection against various life-threatening diseases in pregnant women and their children. A number of studies to improve prevention rates and expand protection against the largest possible number of infections are still in progress. The complex unicity of the mother-infant interaction, both during and after pregnancy and which involves immune system cells and molecules, is an able partner in the success of maternal immunization, as intended thus far. Interestingly, new studies have shed light on the versatility of maternal immunization in protecting infants from non-infectious related diseases, such as allergy, asthma and congenital metabolic disorders. However, barely any attempt at applying maternal immunization to the prevention of childhood cancer has been made. The most promising study reported in this new field is a recent proof of concept on the efficacy of maternal immunization in protecting cancer-prone offspring against mammary tumor progression. New investigations into the possibility of exploiting maternal immunization to prevent the onset and/or progression of neuroblastoma, one of the most common childhood malignancies, are therefore justified. Maternal immunization is presented in a new guise in this review. Attention will be focused on its versatility and potential applications in preventing tumor progression in neuroblastoma-prone offspring. Full article
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