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Vaccines, Volume 5, Issue 2 (June 2017)

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Research

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Open AccessArticle Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax
Vaccines 2017, 5(2), 10; doi:10.3390/vaccines5020010
Received: 24 February 2017 / Revised: 18 April 2017 / Accepted: 21 April 2017 / Published: 2 May 2017
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Abstract
Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical
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Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs), which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP) as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt), formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines. Full article
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Open AccessCommunication The Effect of Physicochemical Modification on the Function of Antibodies Induced by Anti-Nicotine Vaccine in Mice
Vaccines 2017, 5(2), 11; doi:10.3390/vaccines5020011
Received: 28 March 2017 / Revised: 3 May 2017 / Accepted: 11 May 2017 / Published: 17 May 2017
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Abstract
Smoking remains one of the major causes of morbidity and mortality worldwide. One approach to assisting smoking cessation is via anti-nicotine vaccines, composed of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We have previously shown that the carrier, hapten, linker, hapten
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Smoking remains one of the major causes of morbidity and mortality worldwide. One approach to assisting smoking cessation is via anti-nicotine vaccines, composed of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We have previously shown that the carrier, hapten, linker, hapten load, degree of conjugate aggregation, and presence of adducts can each influence the function (nicotine-binding capacity) of the antibody (Ab) induced. Herein, we extend those findings and show that tertiary structure is also critical to the induction of functional immune responses and that this can be influenced by conjugation conditions. We evaluated immunogenicity in mice using six lots of NIC7-CRM, a conjugate of 5-aminoethoxy-nicotine (Hapten 7), and a single point (glycine 52 to glutamic acid) mutant nontoxic form of diphtheria toxin, cross-reactive material 197 (CRM197), which were synthesized under different reaction conditions resulting in conjugates with equivalent molecular characteristics (hapten load, aggregates, adducts), but a different tertiary structure. When tested in mice, better functional responses (reduced nicotine in the brain of immunized animals relative to non-immunized controls) were obtained with conjugates with a more closed structure than those with an open conformation. These studies highlight the need for a better understanding of the physicochemical properties of small molecule conjugate vaccines. Full article
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Open AccessArticle Unexpected Infection Spikes in a Model of Respiratory Syncytial Virus Vaccination
Vaccines 2017, 5(2), 12; doi:10.3390/vaccines5020012
Received: 9 November 2016 / Revised: 6 February 2017 / Accepted: 15 May 2017 / Published: 18 May 2017
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Abstract
Respiratory Syncytial Virus (RSV) is an acute respiratory infection that infects millions of children and infants worldwide. Recent research has shown promise for the development of a vaccine, with a range of vaccine types now in clinical trials or preclinical development. We extend
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Respiratory Syncytial Virus (RSV) is an acute respiratory infection that infects millions of children and infants worldwide. Recent research has shown promise for the development of a vaccine, with a range of vaccine types now in clinical trials or preclinical development. We extend an existing mathematical model with seasonal transmission to include vaccination. We model vaccination both as a continuous process, applying the vaccine during pregnancy, and as a discrete one, using impulsive differential equations, applying pulse vaccination. We develop conditions for the stability of the disease-free equilibrium and show that this equilibrium can be destabilised under certain extreme conditions, even with 100% coverage using an (unrealistic) vaccine. Using impulsive differential equations and introducing a new quantity, the impulsive reproduction number, we showed that eradication could be acheived with 75% coverage, while 50% coverage resulted in low-level oscillations. A vaccine that targets RSV infection has the potential to significantly reduce the overall prevalence of the disease, but appropriate coverage is critical. Full article
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Open AccessArticle The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States
Vaccines 2017, 5(2), 13; doi:10.3390/vaccines5020013
Received: 24 March 2017 / Revised: 7 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
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Abstract
This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and
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This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value. Full article
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Open AccessArticle Reemergence of Measles in the Americas: The Genotype B3 2011–2012 Outbreak in Ecuador
Vaccines 2017, 5(2), 15; doi:10.3390/vaccines5020015
Received: 20 March 2017 / Revised: 24 May 2017 / Accepted: 27 May 2017 / Published: 2 June 2017
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Abstract
This study characterizes a measles outbreak which occurred in Ecuador in 2011–2012, analyzing data from 3700 suspected cases of measles reported to Ecuador’s Ministry of Public Health. The study population had a large age range and included 333 confirmed cases of measles. The
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This study characterizes a measles outbreak which occurred in Ecuador in 2011–2012, analyzing data from 3700 suspected cases of measles reported to Ecuador’s Ministry of Public Health. The study population had a large age range and included 333 confirmed cases of measles. The greatest number of cases were found in the <1 year (32.43%, n = 108) and 1–4 year (30.03%, n = 100) age-groups. Compared to Mestizos, indigenous people had the highest number of cases (68.2%, n = 227), as well as a higher risk of infection (OR 7.278 (CI 5.251–10.087)). The greatest protection from measles was observed in individuals who received two doses of the measles vaccine. Residents of Pastaza (OR 6.645 CI (3.183–13.873)) and Tungurahua (OR 8.346 CI (5.570–12.507)) had a higher risk of infection than the other provinces. Of the 17 laboratory confirmed cases, all were identified as genotype B3. Age-group, ethnicity, measles vaccinations, and residence in Tungurahua and Pastaza were correlated with rates of measles infection in the outbreak. Tungurahua and Pastaza, where the outbreak originated, have large indigenous populations. Indigenous children <1 year of age showed the highest incidence. It is likely that indigenous women do not have immunity to the virus, and so are unable to confer measles resistance to their newborns. Full article
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Review

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Open AccessReview Oncolytic Alphaviruses in Cancer Immunotherapy
Vaccines 2017, 5(2), 9; doi:10.3390/vaccines5020009
Received: 15 March 2017 / Revised: 6 April 2017 / Accepted: 7 April 2017 / Published: 12 April 2017
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Abstract
Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles.
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Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles. Immunization studies in experimental rodent models for various cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and lung cancer as well as melanoma have been conducted with naturally occurring oncolytic alphavirus strains such as M1 and Sindbis AR339. Moreover, animals were vaccinated with engineered oncolytic replication-deficient and -competent Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus vectors expressing various antigens. Vaccinations elicited strong antibody responses and resulted in tumor growth inhibition, tumor regression and even complete tumor eradication. Vaccination also led to prolonged survival in several animal models. Furthermore, preclinical evaluation demonstrated both prophylactic and therapeutic efficacy of oncolytic alphavirus administration. Clinical trials in humans have mainly been limited to safety studies so far. Full article
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Open AccessReview Disease Prevention: An Opportunity to Expand Edible Plant-Based Vaccines?
Vaccines 2017, 5(2), 14; doi:10.3390/vaccines5020014
Received: 17 February 2017 / Revised: 19 May 2017 / Accepted: 23 May 2017 / Published: 30 May 2017
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Abstract
The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control
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The lethality of infectious diseases has decreased due to the implementation of crucial sanitary procedures such as vaccination. However, the resurgence of pathogenic diseases in different parts of the world has revealed the importance of identifying novel, rapid, and concrete solutions for control and prevention. Edible vaccines pose an interesting alternative that could overcome some of the constraints of traditional vaccines. The term “edible vaccine” refers to the use of edible parts of a plant that has been genetically modified to produce specific components of a particular pathogen to generate protection against a disease. The aim of this review is to present and critically examine “edible vaccines” as an option for global immunization against pathogenic diseases and their outbreaks and to discuss the necessary steps for their production and control and the list of plants that may already be used as edible vaccines. Additionally, this review discusses the required standards and ethical regulations as well as the advantages and disadvantages associated with this powerful biotechnology tool. Full article
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