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Vaccines, Volume 6, Issue 1 (March 2018)

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Open AccessArticle Immunogenicity in African Green Monkeys of M Protein Mutant Vesicular Stomatitis Virus Vectors and Contribution of Vector-Encoded Flagellin
Received: 26 February 2018 / Revised: 16 March 2018 / Accepted: 18 March 2018 / Published: 19 March 2018
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Abstract
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We
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Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination. In this report, the immunogenicity of M51R vectors and the adjuvant effect of virus-produced flagellin were evaluated in nonhuman primates following high-dose (108 pfu) and low-dose (105 pfu) vaccination. A single intramuscular vaccination of African green monkeys with M51R or M51R-F induced VSV-specific, dose-dependent humoral immune responses. Flagellin induced a significant increase in antibody production (IgM, IgG and neutralizing antibody) at the low vaccination dose. A VSV-specific cellular response was detected at 6 weeks post-vaccination, but was neither dose-dependent nor enhanced by flagellin; similar numbers of VSV-specific, IFNγ-producing cells were detected in lymph node and spleen of all animals. These results indicate that virus-directed, intracellular flagellin production may improve VSV-based vaccines encoding heterologous antigens by lowering the dose required to achieve humoral immunity. Full article
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Open AccessLetter Hepatitis B At-Birth Dose Vaccine: An Urgent Call for Implementation in Ghana
Received: 7 January 2018 / Revised: 15 February 2018 / Accepted: 21 February 2018 / Published: 12 March 2018
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Abstract
Globally, approximately two billion people are infected with the Hepatitis B virus with attributable death estimated at about half a million people annually across the globe. Chronic hepatitis B infection is also an important public health problem in Ghana. The main mode of
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Globally, approximately two billion people are infected with the Hepatitis B virus with attributable death estimated at about half a million people annually across the globe. Chronic hepatitis B infection is also an important public health problem in Ghana. The main mode of transmission in endemic regions is the perinatal route. Mother-to-child transmission can be reduced by antiviral therapy especially in the last trimester and adherence to the national immunization schedule. The World Health Organization recommends to add the birth dose vaccine to the current expanded program on immunization (EPI) in all countries but especially for endemic regions. The evidence for the efficacy of the birth dose HBV vaccine is overwhelming and there is an urgent need for its introduction into the current EPI schedule in Ghana. Full article
Open AccessReview Immunogenicity and Safety of the New Inactivated Quadrivalent Influenza Vaccine Vaxigrip Tetra: Preliminary Results in Children ≥6 Months and Older Adults
Received: 2 February 2018 / Revised: 26 February 2018 / Accepted: 5 March 2018 / Published: 8 March 2018
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Abstract
Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs). This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs), to enhance protection against circulating influenza B viruses.
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Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs). This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs), to enhance protection against circulating influenza B viruses. This review describes the results obtained from seven phase III clinical trials evaluating the immunogenicity, safety, and lot-to-lot consistency of a new quadrivalent split-virion influenza vaccine (Vaxigrip Tetra®) formulated by adding a second B strain to the already licensed TIV. Since Vaxigrip Tetra was developed by means of a manufacturing process strictly related to that used for TIV, the data on the safety profile of TIV are considered supportive of that of Vaxigrip Tetra. The safety and immunogenicity of Vaxigrip Tetra were similar to those of the corresponding licensed TIV. Moreover, the new vaccine elicits a superior immune response towards the additional strain, without affecting immunogenicity towards the other three strains. Vaxigrip Tetra is well tolerated, has aroused no safety concerns, and is recommended for the active immunization of individuals aged ≥6 months. In addition, preliminary data confirm its immunogenicity and safety even in children aged 6–35 months and its immunogenicity in older subjects (aged 66–80 years). Full article
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Open AccessReview The Emerging Role of Pattern Recognition Receptors in the Pathogenesis of Malaria
Received: 16 January 2018 / Revised: 19 February 2018 / Accepted: 22 February 2018 / Published: 28 February 2018
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Abstract
Despite a global effort to develop an effective vaccine, malaria is still a significant health problem. Much of the pathology of malaria is immune mediated. This suggests that host immune responses have to be finely regulated. The innate immune system initiates and sets
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Despite a global effort to develop an effective vaccine, malaria is still a significant health problem. Much of the pathology of malaria is immune mediated. This suggests that host immune responses have to be finely regulated. The innate immune system initiates and sets the threshold of the acquired immune response and determines the outcome of the disease. Yet, our knowledge of the regulation of innate immune responses during malaria is limited. Theoretically, inadequate activation of the innate immune system could result in unrestrained parasite growth. Conversely, hyperactivation of the innate immune system, is likely to cause excessive production of proinflammatory cytokines and severe pathology. Toll-like receptors (TLRs) have emerged as essential receptors which detect signature molecules and shape the complex host response during malaria infection. This review will highlight the mechanisms by which Plasmodium components are recognized by innate immune receptors with particular emphasis on TLRs. A thorough understanding of the complex roles of TLRs in malaria may allow the delineation of pathological versus protective host responses and enhance the efficacy of anti-malarial treatments and vaccines. Full article
(This article belongs to the Special Issue TLR signaling in Immune Response)
Open AccessReview Meningococcal Vaccines: Current Status and Emerging Strategies
Received: 30 January 2018 / Revised: 21 February 2018 / Accepted: 23 February 2018 / Published: 25 February 2018
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Abstract
Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five
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Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future. Full article
(This article belongs to the collection Vaccines Against Chronic and Persistent Bacterial Infections)
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Open AccessReview Repurposing Plant Virus Nanoparticles
Received: 23 December 2017 / Revised: 26 January 2018 / Accepted: 2 February 2018 / Published: 14 February 2018
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Abstract
Plants have been explored for many years as inexpensive and versatile platforms for the generation of vaccines and other biopharmaceuticals. Plant viruses have also been engineered to either express subunit vaccines or act as epitope presentation systems. Both icosahedral and helical, filamentous-shaped plant
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Plants have been explored for many years as inexpensive and versatile platforms for the generation of vaccines and other biopharmaceuticals. Plant viruses have also been engineered to either express subunit vaccines or act as epitope presentation systems. Both icosahedral and helical, filamentous-shaped plant viruses have been used for these purposes. More recently, plant viruses have been utilized as nanoparticles to transport drugs and active molecules into cancer cells. The following review describes the use of both icosahedral and helical plant viruses in a variety of new functions against cancer. The review illustrates the breadth of variation among different plant virus nanoparticles and how this impacts the immune response. Full article
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Open AccessReview Virus-Like-Vaccines against HIV
Received: 4 January 2018 / Revised: 2 February 2018 / Accepted: 10 February 2018 / Published: 11 February 2018
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Abstract
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have
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Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8+ and CD4+ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response. Full article
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Open AccessReview Radiation and Anti-Cancer Vaccines: A Winning Combination
Received: 5 December 2017 / Revised: 22 January 2018 / Accepted: 26 January 2018 / Published: 30 January 2018
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Abstract
The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations
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The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future. Full article
Open AccessReview Challenges and Achievements in Prevention and Treatment of Smallpox
Received: 11 December 2017 / Revised: 15 January 2018 / Accepted: 26 January 2018 / Published: 29 January 2018
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Abstract
Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional
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Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions. Full article
Open AccessReview Development of Zika Virus Vaccines
Received: 23 November 2017 / Revised: 12 January 2018 / Accepted: 14 January 2018 / Published: 18 January 2018
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Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré
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Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines. Full article
Open AccessReview Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and Potential Therapeutic Use for Chronic Hepatitis B
Received: 10 December 2017 / Revised: 6 January 2018 / Accepted: 11 January 2018 / Published: 16 January 2018
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Abstract
Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV
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Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines. Recent studies show that the activation of TLR-mediated signaling pathways results in a suppression of HBV replication in vitro and in vivo. However, HBV has also evolved strategies to counter TLR responses including the suppression of TLR expression and the blockage of downstream signaling pathways. Antiviral treatment in chronic HBV-infected patients leads to an upregulation of TLR expression and the restoration of its innate antiviral functions. Thus, TLR activation may serve as an additional immunotherapeutic option for treating chronic HBV infection in combination with antiviral treatment. Full article
(This article belongs to the Special Issue TLR signaling in Immune Response)
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Open AccessArticle Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice
Received: 26 November 2017 / Revised: 4 January 2018 / Accepted: 6 January 2018 / Published: 10 January 2018
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Abstract
Burkholderia mallei is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, B. mallei is
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Burkholderia mallei is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, B. mallei is classified as one of the most important bacterial biothreat agents. Presently, there is no licensed glanders vaccine available for humans or animals. In this work, outer membrane vesicles (OMVs) were isolated from three attenuated biosafe bacterial strains, Burkholderia pseudomallei Bp82, B. thailandensis E555, and B. thailandensis TxDOH and used to vaccinate mice. B. thailandensis OMVs induced significantly higher antibody responses that were investigated. B. mallei specific serum antibody responses were of higher magnitude in mice vaccinated with B. thailandensis OMVs compared to levels in mice vaccinated with B. pseudomallei OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two B. thailandensis strains affording significant protection (>90%) up to 35 days post-infection with some up to 60 days. Organ loads from 35-day survivors indicated bacteria colonization of the lungs, liver, and spleen while those from 60 days had high CFUs in the spleens. The highest antibody producing vaccine (B. thailandensis E555 OMVs) also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection. Full article
(This article belongs to the collection Vaccines Against Chronic and Persistent Bacterial Infections)
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Open AccessEditorial Acknowledgement to Reviewers of Vaccines in 2017
Received: 9 January 2018 / Revised: 9 January 2018 / Accepted: 9 January 2018 / Published: 9 January 2018
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Abstract
Peer review is an essential part in the publication process, ensuring that Vaccines maintains high quality standards for its published papers.[...] Full article
Open AccessArticle Influenza Vaccination Rates Among Parents and Health Care Personnel in a German Neonatology Department
Received: 13 November 2017 / Revised: 1 January 2018 / Accepted: 3 January 2018 / Published: 5 January 2018
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Abstract
The influenza vaccination is recommended for all German pregnant women and health care personnel (HCP). We are the first to publish vaccination rates of mothers of hospitalized newborns and HCP in neonatal units. Between September 2016 and March 2017, data were collected in
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The influenza vaccination is recommended for all German pregnant women and health care personnel (HCP). We are the first to publish vaccination rates of mothers of hospitalized newborns and HCP in neonatal units. Between September 2016 and March 2017, data were collected in our level-III neonatology department in this descriptive multidisciplinary study, using an anonymous questionnaire. As a result, 513 persons were asked to participate, including 330 parents and 183 HCP. We received an 80.3% (412/513) response rate, 87.3% (288/330), and 67.8% (124/183) from parents and HCP, respectively. Ten percent (16/160) of mothers and 4.7% (6/127) of fathers had been vaccinated in 2016–2017 and 54.4% (87/160) mothers and 52.2% (66/127) fathers ever in their lifetime. In 2016–2017, 51.2% (21/41) of physicians had been vaccinated, 25.5% (14/55) of nurses, and 50.0% (14/28) of other staff members. When comparing those who had more than five influenza vaccinations in their life time, physicians were at 43.9% (18/41) versus nurses at 10.9% (6/55) (p < 0.01), and other HCP at 7.4% (2/27) (p < 0.01). The influenza vaccine uptake rate of 10% in mothers of hospitalized neonates is disappointingly low, resulting in 90% of hospitalized neonates being potentially vulnerable to influenza infection at a time where the risk for influenza-related complication can be severe. Full article
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Open AccessArticle Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
Received: 30 October 2017 / Revised: 2 December 2017 / Accepted: 21 December 2017 / Published: 25 December 2017
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Abstract
Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development
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Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against Chlamydia is crucial. Whole organism-based vaccines have short-lived activity, serovar/subgroup-specific immunity and can cause adverse reactions in vaccinated subjects. The Chlamydia major outer membrane protein (MOMP) is a prime candidate for a subunit vaccine. MOMP contains four regions of sequence variability (variable domains, VDs) with B-cell and T-cell epitopes that elicit protective immunity. However, barriers for developing a MOMP-based vaccine include solubility, yield and refolding. We have engineered novel recombinant antigens in which the VDs are expressed into a carrier protein structurally similar to MOMP and suitable for recombinant expression at a high yield in a correctly folded and detergent-free form. Using a carrier such as the PorB porin from the human commensal organism N. lactamica, we show that PorB/VD chimeric proteins are immunogenic, antigenic and cross-reactive with MOMP. VDs are unique for each serovar but if combined in a single vaccine, a broad coverage against the major Chlamydia serovars can be ensured. Full article
(This article belongs to the Special Issue TLR signaling in Immune Response)
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Open AccessArticle Structural Analysis and Epitope Prediction of MHC Class-1-Chain Related Protein-A for Cancer Vaccine Development
Received: 31 October 2017 / Revised: 16 November 2017 / Accepted: 21 November 2017 / Published: 25 December 2017
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Abstract
Major histocompatibility complex class 1 chain-related gene sequence A is a polymorphic gene found at about 46.6 kb centromeric to HLA-B. It encodes a transmembrane protein, which is a non-classical human leukocyte antigen whose expression is normally induced by stress conditions like cancer
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Major histocompatibility complex class 1 chain-related gene sequence A is a polymorphic gene found at about 46.6 kb centromeric to HLA-B. It encodes a transmembrane protein, which is a non-classical human leukocyte antigen whose expression is normally induced by stress conditions like cancer and viral infections. The expression of MIC-A leads to the activation of NKG2D receptors of natural killer and T cells, leading to the generation of innate immune response that can easily eliminate/cleanse tumour cells and other cells that express the protein. Several bioinformatics and immunoinformatics tools were used to analyse the sequence and structure of the MIC-A protein. These tools were used in building and evaluating modelled structure of MIC-A, and to predict several antigenic determinant sites on the protein. The MIC-A protein structure generated an average antigenic propensity of 1.0289. Additionally, the hydrophilic regions on the surface of the MIC-A protein where antibodies can be attached were revealed. A total of fourteen antigenic epitopes were predicted, with six found in the transmembrane protein topology, and are predicted to play a role in the development of vaccines that can reactivate the functionalities of the MIC-A protein on the surface of cancer cells in order to elicit a desired immune response. Full article
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