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Vaccines, Volume 8, Issue 3 (September 2020) – 216 articles

Cover Story (view full-size image): Zika virus (ZIKV) is the etiological agent responsible for a range of debilitating and often lifelong birth defects collectively termed congenital Zika syndrome (CZS). Although the ZIKV pandemic has subsided, ZIKV continues to be a burden, with 87 countries and territories now displaying autochthonous ZIKV transmission and no commercial vaccine is currently available. This paper uses a recently designed flavivirus chimeric platform comprising the backbone of an Australian mosquito virus, Binjari virus, to generate a ZIKV vaccine candidate named BinJ/ZIKV-prME. This vaccine, administered unadjuvanted and as a single dose, protected against fetal ZIKV infection and did not cause antibody-dependent enhancement of dengue infection and disease in mice. BinJ/ZIKA-prME thus emerges as a potential vaccine candidate for the prevention of CSZ. View this paper.
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Article
Impact of COVID-19 on Immunization Services for Maternal and Infant Vaccines: Results of a Survey Conducted by Imprint—The Immunising Pregnant Women and Infants Network
Vaccines 2020, 8(3), 556; https://doi.org/10.3390/vaccines8030556 - 22 Sep 2020
Cited by 16 | Viewed by 2740
Abstract
The COVID-19 pandemic response has caused disruption to healthcare services globally, including to routine immunizations. To understand immunization service interruptions specifically for maternal, neonatal and infant vaccines, we captured the local experiences of members of the Immunising Pregnant Women and Infants Network (IMPRINT) [...] Read more.
The COVID-19 pandemic response has caused disruption to healthcare services globally, including to routine immunizations. To understand immunization service interruptions specifically for maternal, neonatal and infant vaccines, we captured the local experiences of members of the Immunising Pregnant Women and Infants Network (IMPRINT) by conducting an online survey over 2-weeks in April 2020. IMPRINT is a global network of clinicians and scientists working in maternal and neonatal vaccinology. The survey included discrete questions to quantify the extent of disruption as well as free-text options to explore the reasons behind reported disruptions. Of the 48 responses received, the majority (75%) were from low-and-middle-income countries (LMICs). Of all respondents, 50% or more reported issues with vaccine delivery within their country. Thematic analysis identified three key themes behind immunization disruption: “access” issues, e.g., logistical barriers, “provider” issues, e.g., staff shortages and user “concern” about attending immunization appointments due to COVID-19 fear. Access and provider issues were more commonly reported by LMIC respondents. Overall, respondents reported uncertainty among parents and healthcare providers regarding routine immunization. We conclude that further quantification of routine vaccination disruption is needed, alongside health service prioritization, logistical support and targeted communication strategies to reinforce routine immunizations during the COVID-19 response. Full article
(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)
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Review
Advances in the Development of Anti-Haemonchus contortus Vaccines: Challenges, Opportunities, and Perspectives
Vaccines 2020, 8(3), 555; https://doi.org/10.3390/vaccines8030555 - 22 Sep 2020
Cited by 3 | Viewed by 1542
Abstract
The gastrointestinal nematode parasite Haemonchus contortus (H. contortus) is a resident of tropical and subtropical regions worldwide that imposes significant production losses, economic losses, and animal health issues in the small ruminant industry, particularly sheep and goats. Considerable efforts have been [...] Read more.
The gastrointestinal nematode parasite Haemonchus contortus (H. contortus) is a resident of tropical and subtropical regions worldwide that imposes significant production losses, economic losses, and animal health issues in the small ruminant industry, particularly sheep and goats. Considerable efforts have been made to understand how immunity is elicited against H. contortus infection. Various potential vaccine antigens have been tested by different methods and strategies applied in animal models, and significant progress has been made in the development of vaccines against H. contortus. This review highlighted and shared the knowledge about the current understanding of host immune responses to H. contortus and ongoing challenges in the development of a protective, effective, and long-lasting vaccine against H. contortus infection. We have also pinpointed some achievements and failures in the development and testing of vaccines, which will establish a road map for future research directions to explore new effective vaccine candidates for controlling and preventing H. contortus infection. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Review
Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants
Vaccines 2020, 8(3), 554; https://doi.org/10.3390/vaccines8030554 - 22 Sep 2020
Cited by 4 | Viewed by 1553
Abstract
In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most [...] Read more.
In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection. Thus, improved understanding of vaccine adjuvant mechanisms may aid in the design of “intelligent” vaccines to provide robust protection from pathogens. Various commonly used clinical adjuvants, such as aluminium salts, saponins or emulsions, have been identified as activators of inflammasomes - multiprotein signalling platforms that drive activation of inflammatory caspases, resulting in secretion of pro-inflammatory cytokines of the IL-1 family. Importantly, these cytokines affect the cellular and humoral arms of adaptive immunity, which indicates that inflammasomes represent a valuable target of vaccine adjuvants. In this review, we highlight the impact of different inflammasomes on vaccine adjuvant-induced immune responses regarding their mechanisms and immunogenicity. In this context, we focus on clinically relevant adjuvants that have been shown to activate the NLRP3 inflammasome and also present various experimental adjuvants that activate the NLRP3-, NLRC4-, AIM2-, pyrin-, or non-canonical inflammasomes and could have the potential to improve future vaccines. Together, we provide a comprehensive overview on vaccine adjuvants that are known, or suggested, to promote immunogenicity through inflammasome-mediated signalling. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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Review
Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines
Vaccines 2020, 8(3), 553; https://doi.org/10.3390/vaccines8030553 - 22 Sep 2020
Cited by 8 | Viewed by 1247
Abstract
Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe [...] Read more.
Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause. Full article
(This article belongs to the Special Issue Vaccine Candidates against Tropical Diseases)
Article
Enhancement of Immune Response and Anti-Infection of Mice by Porcine Antimicrobial Peptides and Interleukin-4/6 Fusion Gene Encapsulated in Chitosan Nanoparticles
Vaccines 2020, 8(3), 552; https://doi.org/10.3390/vaccines8030552 - 21 Sep 2020
Cited by 3 | Viewed by 1043
Abstract
In order to develop a novel and effective immunoregulator to enhance both the immune response and antimicrobial function, a recombinant eukaryotic expression plasmid-pVAX1 co-expressing fusion cathelicidin antimicrobial peptides (CAMPs) and fusion porcine interleukin-4/6 gene (IL-4/6) was constructed and encapsulated in chitosan nanoparticles (CS-VAP4/6), [...] Read more.
In order to develop a novel and effective immunoregulator to enhance both the immune response and antimicrobial function, a recombinant eukaryotic expression plasmid-pVAX1 co-expressing fusion cathelicidin antimicrobial peptides (CAMPs) and fusion porcine interleukin-4/6 gene (IL-4/6) was constructed and encapsulated in chitosan nanoparticles (CS-VAP4/6), prepared by the ionotropic gelation method. Four-week-old female Kunming mice were divided into three groups and intramuscularly injected, respectively, with CS-VAP, CS-VAP4/6, and CS-pVAX1. On 28 days post-inoculation, the mice were challenged by intraperitoneal injection with Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922); IgG, IgG1 and IgG2a, CD4+, and CD8+ T cells increased significantly in the VAP- and VAP4/6- treated mice, detected by ELISA and flow cytometry, correspondingly (p < 0.05). As analyzed by qPCR, expression levels of Toll-like receptor (TLR) 1, TLR4, TLR6, TLR9, IL-1, IL-2, IL-4, IL-6, IL-7, IL-12, IL-15, IL-23, Tumor Necrosis Factor (TNF)-α, and Interferon-gamma (IFN-γ) genes were also significantly up-regulated in comparison with those of the control mice (p < 0.05). Their immunological markers were elevated significantly to different degrees in CS-VAP4/6-treated mice compared with CS-VAP in different days post-inoculation (p < 0.05). After challenge with E. coli and Staphylococcus aureus, most of the VAP- and VAP4/6- treated mice survived, and no symptoms of bacterial infection were observed. In contrast, 80% of control mice died of infection. Among the treated groups, VAP4/6 had a stronger resistance against challenge with E. coli infection. These results demonstrated that the fusion gene of antimicrobial peptide and interleukin-4/6 has the promising potential as a safe and effective immunomodulator for the control of bacterial infections. Full article
(This article belongs to the Special Issue Vaccines against Antimicrobial-Resistant Infections)
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Article
Solid Lipid Nanoparticle Carrier Platform Containing Synthetic TLR4 Agonist Mediates Non-Viral DNA Vaccine Delivery
Vaccines 2020, 8(3), 551; https://doi.org/10.3390/vaccines8030551 - 21 Sep 2020
Cited by 1 | Viewed by 1373
Abstract
There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for [...] Read more.
There is a growing demand for better delivery systems to improve the stability and efficacy of DNA vaccines. Here we report the synthesis of a non-viral DNA vaccine delivery system using a novel adjuvanted solid lipid nanoparticle (SLN-A) platform as a carrier for a DNA vaccine candidate encoding the Urease alpha (UreA) antigen from Helicobacter pylori. Cationic SLN-A particles containing monophosphoryl lipid A (adjuvant) were synthesised by a modified solvent-emulsification method and were investigated for their morphology, zeta potential and in vitro transfection capacity. Particles were found to bind plasmid DNA to form lipoplexes, which were characterised by electron microscopy, dynamic light scattering and fluorescence microscopy. Cellular uptake studies confirmed particle uptake within 3 h, and intracellular localisation within endosomal compartments. In vitro studies further confirmed the ability of SLN-A particles to stimulate expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in human macrophage-like Tohoku Hospital Pediatrics-1 (THP-1) cells. Lipoplexes were found to be biocompatible and could be efficiently transfected in murine immune cells for expression of recombinant H. pylori antigen Urease A, demonstrating their potential as a DNA vaccine delivery system. Full article
(This article belongs to the Special Issue Vaccines for Infectious and Chronic Diseases)
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Review
The Role of Birds of Prey in West Nile Virus Epidemiology
Vaccines 2020, 8(3), 550; https://doi.org/10.3390/vaccines8030550 - 21 Sep 2020
Cited by 6 | Viewed by 1513
Abstract
Reported human cases of West Nile virus (WNV) in Europe increased dramatically in 2018. Lineage 1 strains had been circulating in Euro-Mediterranean countries since the early 1990s. The subsequent introduction of WNV lineage 2 has been responsible for the remarkable upsurge of European [...] Read more.
Reported human cases of West Nile virus (WNV) in Europe increased dramatically in 2018. Lineage 1 strains had been circulating in Euro-Mediterranean countries since the early 1990s. The subsequent introduction of WNV lineage 2 has been responsible for the remarkable upsurge of European WNV outbreaks since 2004, including the dramatic increase in human cases observed since 2018. The virus exists in a natural cycle between mosquitoes and wild birds, with humans and horses acting as dead-end hosts. As the key vertebrate hosts in the transmission cycle of WNV, avian species have been the focus of surveillance across many countries. Raptors appear particularly susceptible to WNV infection, resulting in higher prevalence, and in some cases exhibiting neurological signs that lead to the death of the animal. In addition, birds of prey are known to play an important role as WNV reservoir and potentially amplifying hosts of infection. Importantly, raptor higher susceptibility/prevalence may indicate infection through predation of infected prey. Consequently, they are considered important target species when designing cost-effective surveillance for monitoring both seasonal WNV circulation in endemic countries and its emergence into new areas, where migrating raptors may play a critical role in virus introduction. This review summarizes the different aspects of the current knowledge of WNV infection in birds of prey and evaluates their role in the evolution of the epizootic that is spreading throughout Europe. Full article
(This article belongs to the Special Issue West Nile Virus Disease)
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Article
African Swine Fever Circulation among Free-Ranging Pigs in Sardinia: Data from the Eradication Program
Vaccines 2020, 8(3), 549; https://doi.org/10.3390/vaccines8030549 - 21 Sep 2020
Cited by 7 | Viewed by 1303
Abstract
African swine fever virus (ASFV), the cause of a devastating disease affecting domestic and wild pigs, has been present in Sardinia since 1978. In the framework of the regional ASF eradication plan, 4484 illegal pigs were culled between December 2017 and February 2020. [...] Read more.
African swine fever virus (ASFV), the cause of a devastating disease affecting domestic and wild pigs, has been present in Sardinia since 1978. In the framework of the regional ASF eradication plan, 4484 illegal pigs were culled between December 2017 and February 2020. The highest disease prevalence was observed in the municipality with the highest free-ranging pig density, and culling actions drastically reduced ASFV circulation among these animals. ASFV-antibody were detected in 36.7% of tested animals, which were apparently healthy, thus, the circulation of low-virulence ASFV isolates was hypothesized. ASFV genome was detected in 53 out of 2726 tested animals, and virus isolation was achieved in two distinct culling actions. Two ASFV haemadsorbing strains were isolated from antibody-positive apparently healthy pigs: 55234/18 and 103917/18. Typing analysis revealed that both isolates belong to p72 genotype I, B602L subgroup X; phylogenetic analysis based on whole genome sequencing data showed that they were closely related to Sardinian ASFV strains collected since 2010, especially 22653/Ca/2014. Our data suggested the absence of immune-escaped ASFV variants circulating among free-ranging pigs, indicating that other elements contributed to virus circulation among these animals. Understanding factors behind disease persistence in endemic settings might contribute to developing effective countermeasures against this disease. Full article
(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)
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Review
Influenza–Host Interplay and Strategies for Universal Vaccine Development
Vaccines 2020, 8(3), 548; https://doi.org/10.3390/vaccines8030548 - 20 Sep 2020
Cited by 2 | Viewed by 1532
Abstract
Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus [...] Read more.
Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus hemagglutinin (HA) glycoprotein that binds to the cellular sialic acid receptors and facilitates the fusion of the viral membrane with the endosomal membrane. During IAV infection, virus-derived pathogen-associated molecular patterns (PAMPs) are recognized by host intracellular specific sensors including toll-like receptors (TLRs), C-type lectin receptors, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) either on the cell surface or intracellularly in endosomes. Herein, we comprehensively review the current knowledge available on the entry of the influenza virus into host cells and the molecular details of the influenza virus–host interface. We also highlight certain strategies for the development of universal influenza vaccines. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Antibody Response to Canine Parvovirus Vaccination in Dogs with Hyperadrenocorticism Treated with Trilostane
Vaccines 2020, 8(3), 547; https://doi.org/10.3390/vaccines8030547 - 19 Sep 2020
Cited by 5 | Viewed by 1030
Abstract
It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs [...] Read more.
It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs with HAC, and healthy age-matched control dogs (n = 31) received a modified-live CPV vaccine. Antibodies were determined on days 0, 7, and 28 by hemagglutination inhibition. Univariate analysis was used to compare the immune response of dogs with HAC and healthy dogs. Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HAC (11/11; 95% CI: 70.0–100) and in 93.5% of healthy dogs (29/31; 95% CI: 78.3–99.2). No ≥4-fold increase in antibody titer was observed in dogs with HAC while in 22.6% of healthy dogs, a ≥4-fold titer increase was observed (7/31; 95% CI: 11.1–40.1). Mild vaccine-associated adverse events (VAAEs) were detected in 54.5% of dogs with HAC (6/11; 95% CI: 28.0–78.8) and in 29.0% of healthy dogs (9/31; 95% CI: 15.9–46.8). There was neither a significant difference in presence of pre-vaccination antibodies (p = 1.000), or response to vaccination (p = 0.161), nor in the occurrence of VAAEs (p = 0.158). Immune function of dogs with HAC treated with trilostane seems comparable to that of healthy dogs. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
Review
The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?
Vaccines 2020, 8(3), 546; https://doi.org/10.3390/vaccines8030546 - 19 Sep 2020
Cited by 1 | Viewed by 1043
Abstract
Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system, and lack of previous exposure to the virus is thought to synergistically play a role in the increased disease severity [...] Read more.
Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system, and lack of previous exposure to the virus is thought to synergistically play a role in the increased disease severity in younger age groups. No influenza vaccines are available for those under six months, although maternal influenza immunization is recommended. In children aged six months to two years, vaccine immunogenicity is dampened compared to older children and adults. Unlike older children and adults, the infant immune system has fewer antigen-presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. We contend that by understanding the influenza imprinting event in the context of the infant immune system, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune and respiratory development, current vaccine strategies, and highlights the importance of research into the imprinting event in infant animal models to develop more effective and protective vaccines for all including young children. Full article
(This article belongs to the Special Issue Vaccinology of Influenza Infection)
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Editorial
Vaccination and Vaccine Effectiveness: A Commentary of Special Issue Editors
Vaccines 2020, 8(3), 545; https://doi.org/10.3390/vaccines8030545 - 18 Sep 2020
Cited by 1 | Viewed by 1422
Abstract
The Special Issue “Vaccination and Vaccine Effectiveness”, published in the journal Vaccines, has the main aim to increase international literature data on vaccine effectiveness and safety and on vaccination strategies in order to reduce vaccine hesitancy and improve vaccination coverage rates. The [...] Read more.
The Special Issue “Vaccination and Vaccine Effectiveness”, published in the journal Vaccines, has the main aim to increase international literature data on vaccine effectiveness and safety and on vaccination strategies in order to reduce vaccine hesitancy and improve vaccination coverage rates. The main topics included in the call for papers were vaccines administered to infants, adolescents, adults, elderly people, at-risk populations (due to comorbidities and personal risk factors) and healthcare workers and strategies adopted to promote vaccination adherence among these categories. This Special Issue started from the assumption that, despite vaccination being universally recognized as one of the best strategies to increase duration and quality of life during the last centuries, vaccination coverage rates are often under the levels recommended to reduce circulation and to extinguish vaccine-preventable diseases. Vaccine hesitancy involves at least 15% of the general population, and healthcare workers also sometimes demonstrate doubts on vaccination effectiveness and safety. At the end of the six-month submission period, 16 articles (15 research article and one review) were accepted after the peer-review processes and published online. Full article
(This article belongs to the Special Issue Vaccination and Vaccine Effectiveness)
Case Report
Pneumocystis jirevocii and SARS-CoV-2 Co-Infection: A Common Feature in Transplant Recipients?
Vaccines 2020, 8(3), 544; https://doi.org/10.3390/vaccines8030544 - 18 Sep 2020
Cited by 4 | Viewed by 1125
Abstract
COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the [...] Read more.
COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the prognosis and the severity of the disease, and can in turn lead to an increased need of mechanical ventilation, antibiotic therapy and to a higher mortality. Here we describe, for the first time in Europe, a fatal case of co-infection between SARS-CoV-2 and Pneumocystis jirevocii in a kidney transplant recipient. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
Article
Meningococcal Disease and Related Vaccinations: Knowledge, Attitudes, and Practices among Healthcare Workers Who Provide Care to Patients with Underlying High-Risk Medical Conditions
Vaccines 2020, 8(3), 543; https://doi.org/10.3390/vaccines8030543 - 18 Sep 2020
Cited by 3 | Viewed by 901
Abstract
This cross-sectional study assessed knowledge, attitudes, and practices regarding meningococcal disease and related vaccinations among healthcare workers (HCWs) who provided care to patients with underlying high-risk medical conditions. A total of 411 HCWs returned the survey. Only 35% of the respondents had a [...] Read more.
This cross-sectional study assessed knowledge, attitudes, and practices regarding meningococcal disease and related vaccinations among healthcare workers (HCWs) who provided care to patients with underlying high-risk medical conditions. A total of 411 HCWs returned the survey. Only 35% of the respondents had a good knowledge about the incidence and lethality of meningococcal disease, the most frequent serogroups in Italy and the diseases or conditions that expose patients to a high-risk of severe complications caused by meningococcal disease. Vaccination against meningococcal disease was perceived to be highly effective by 38.4% of participants, very safe by 36.2%, and 82% agreed or strongly agreed that HCWs should promote adherence to recommended vaccinations even in hesitant patients. Moreover, 34.1% recommended meningococcal vaccinations to all eligible patients and the results of the multivariate analysis showed that older HCWs, who work in pediatric/neonatal wards, have good knowledge about meningococcal vaccinations, have a favourable attitude towards vaccinations, and do not need additional information about meningococcal vaccinations, were more likely to recommend meningococcal vaccinations to all eligible patients. Interventions aimed at the enhancement of knowledge and awareness of HCWs who provide care to these patients on the benefits of meningococcal vaccinations are warranted. Full article
Article
Control of Cytoskeletal Dynamics by β-Arrestin1/Myosin Vb Signaling Regulates Endosomal Sorting and Scavenging Activity of the Atypical Chemokine Receptor ACKR2
Vaccines 2020, 8(3), 542; https://doi.org/10.3390/vaccines8030542 - 17 Sep 2020
Cited by 1 | Viewed by 917
Abstract
The atypical chemokine receptor ACKR2, formerly named D6, is a scavenger chemokine receptor with a non-redundant role in the control of inflammation and immunity. The scavenging activity of ACKR2 depends on its trafficking properties, which require actin cytoskeleton rearrangements downstream of a β-arrestin1-Rac1-PAK1-LIMK1-cofilin-dependent [...] Read more.
The atypical chemokine receptor ACKR2, formerly named D6, is a scavenger chemokine receptor with a non-redundant role in the control of inflammation and immunity. The scavenging activity of ACKR2 depends on its trafficking properties, which require actin cytoskeleton rearrangements downstream of a β-arrestin1-Rac1-PAK1-LIMK1-cofilin-dependent signaling pathway. We here demonstrate that in basal conditions, ACKR2 trafficking properties require intact actin and microtubules networks. The dynamic turnover of actin filaments is required to sustain ACKR2 constitutive endocytosis, while both actin and microtubule networks are involved in processes regulating ACKR2 constitutive sorting to rapid, Rab4-dependent and slow, Rab11-dependent recycling pathways, respectively. After chemokine engagement, ACKR2 requires myosin Vb activity to promote its trafficking from Rab11-positive recycling endosomes to the plasma membrane, which sustains its scavenging activity. Other than cofilin phosphorylation, induction of the β-arrestin1-dependent signaling pathway by ACKR2 agonists also leads to the rearrangement of microtubules, which is required to support the myosin Vb-dependent ACKR2 upregulation and its scavenging properties. Disruption of the actin-based cytoskeleton by the apoptosis-inducing agent staurosporine results in impaired ACKR2 internalization and chemokine degradation that is consistent with the emerging scavenging-independent activity of the receptor in apoptotic neutrophils instrumental for promoting efficient efferocytosis during the resolution of inflammation. In conclusion, we provide evidence that ACKR2 activates a β-arrestin1-dependent signaling pathway, triggering both the actin and the microtubule cytoskeletal networks, which control its trafficking and scavenger properties. Full article
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Review
Cognitive and Memory Functions in Plant Immunity
Vaccines 2020, 8(3), 541; https://doi.org/10.3390/vaccines8030541 - 17 Sep 2020
Cited by 2 | Viewed by 828
Abstract
From the time of Thucydides in the 5th century BC, it has been known that specific recognition of pathogens and memory formation are critical components of immune functions. In contrast to the immune system of jawed vertebrates, such as humans and mice, plants [...] Read more.
From the time of Thucydides in the 5th century BC, it has been known that specific recognition of pathogens and memory formation are critical components of immune functions. In contrast to the immune system of jawed vertebrates, such as humans and mice, plants lack a circulatory system with mobile immune cells and a repertoire of clonally distributed antigen receptors with almost unlimited specificities. However, without these systems and mechanisms, plants can live and survive in the same hostile environment faced by other organisms. In fact, they achieve specific pathogen recognition and elimination, with limited self-reactivity, and generate immunological memory, sometimes with transgenerational characteristics. Thus, the plant immune system satisfies minimal conditions for constituting an immune system, namely, the recognition of signals in the milieu, integration of that information, subsequent efficient reaction based on the integrated information, and memorization of the experience. In the previous report, this set of elements was proposed as an example of minimal cognitive functions. In this essay, I will first review current understanding of plant immunity and then discuss the unique features of cognitive activities, including recognition of signals from external as well as internal environments, autoimmunity, and memory formation. In doing so, I hope to reach a deeper understanding of the significance of immunity omnipresent in the realm of living organisms. Full article
(This article belongs to the Special Issue Immune Mechanisms in Plants)
Article
GMMA Is a Versatile Platform to Design Effective Multivalent Combination Vaccines
Vaccines 2020, 8(3), 540; https://doi.org/10.3390/vaccines8030540 - 17 Sep 2020
Cited by 12 | Viewed by 1299
Abstract
Technology platforms are an important strategy to facilitate the design, development and implementation of vaccines to combat high-burden diseases that are still a threat for human populations, especially in low- and middle-income countries, and to address the increasing number and global distribution of [...] Read more.
Technology platforms are an important strategy to facilitate the design, development and implementation of vaccines to combat high-burden diseases that are still a threat for human populations, especially in low- and middle-income countries, and to address the increasing number and global distribution of pathogens resistant to antimicrobial drugs. Generalized Modules for Membrane Antigens (GMMA), outer membrane vesicles derived from engineered Gram-negative bacteria, represent an attractive technology to design affordable vaccines. Here, we show that GMMA, decorated with heterologous polysaccharide or protein antigens, leads to a strong and effective antigen-specific humoral immune response in mice. Importantly, GMMA promote enhanced immunogenicity compared to traditional formulations (e.g., recombinant proteins and glycoconjugate vaccines), without negative impact to the anti-GMMA immune response. Our findings support the use of GMMA as a “plug and play” technology for the development of effective combination vaccines targeting different bugs at the same time. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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Article
Akt+ IKKα/β+ Rab5+ Signalosome Mediate the Endosomal Recruitment of Sec61 and Contribute to Cross-Presentation in Bone Marrow Precursor Cells
Vaccines 2020, 8(3), 539; https://doi.org/10.3390/vaccines8030539 - 17 Sep 2020
Cited by 1 | Viewed by 805
Abstract
Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase α/β (IKKα/β) activation, the [...] Read more.
Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase α/β (IKKα/β) activation, the exact roles of Akt phosphorylation, IKKα or IKKβ activation in endotoxin-containing pathogen-derived cross-presentation are poorly understood. In this study, endotoxin-free ovalbumin supplemented with endotoxin was used as a model pathogen. We investigated the effects of endotoxin-containing pathogen and endotoxin-free antigen on Akt phosphorylation, IKKα/β activation, and explored the mechanisms that the endotoxin-containing pathogen orchestrating the endosomal recruitment of Sec61 of the cross-presentation in bone marrow precursor cells (BMPC). We demonstrated that endotoxin-containing pathogen and endotoxin-free antigen efficiently induced the phosphorylation of Akt-IKKα/β and Akt-IKKα, respectively. Endotoxin-containing pathogen derived Akt+ IKKα/β+ Rab5+ signalosome, together with augmented the recruitment of Sec61 toward endosome, lead to the increased cross-presentation in BMPC. Importantly, the endosomal recruitment of Sec61 was partly mediated by the formation of Akt+ IKKα/β+ signalosome. Thus, these data suggest that Akt+ IKKα/β+ Rab5+ signalosome contribute to endotoxin-containing pathogen-induced the endosomal recruitment of Sec61 and the superior efficacy of cross-presentation in BMPC. Full article
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Article
Recognition of Dimeric Lewis X by Anti-Dimeric Lex Antibody SH2
Vaccines 2020, 8(3), 538; https://doi.org/10.3390/vaccines8030538 - 17 Sep 2020
Viewed by 1161
Abstract
The carbohydrate antigen dimeric Lewis X (DimLex), which accumulates in colonic and liver adenocarcinomas, is a valuable target to develop anti-cancer therapeutics. Using the native DimLex antigen as a vaccine would elicit an autoimmune response against the Lex antigen [...] Read more.
The carbohydrate antigen dimeric Lewis X (DimLex), which accumulates in colonic and liver adenocarcinomas, is a valuable target to develop anti-cancer therapeutics. Using the native DimLex antigen as a vaccine would elicit an autoimmune response against the Lex antigen found on normal, healthy cells. Thus, we aim to study the immunogenic potential of DimLex and search internal epitopes displayed by DimLex that remain to be recognized by anti-DimLex monoclonal antibodies (mAbs) but no longer possess epitopes recognized by anti-Lex mAbs. In this context, we attempted to map the epitope recognized by anti-DimLex mAb SH2 by titrations and competitive inhibition experiments using oligosaccharide fragments of DimLex as well as Lex analogues. We compare our results with that reported for anti-Lex mAb SH1 and anti-polymeric Lex mAbs 1G5F6 and 291-2G3-A. While SH1 recognizes an epitope localized to the non-reducing end Lex trisaccharide, SH2, 1G5F6, and 291-2G3-A have greater affinity for DimLex conjugates than for Lex conjugates. We show, however, that the Lex trisaccharide is still an important recognition element for SH2, which (like 1G5F6 and 291-2G3-A) makes contacts with all three sugar units of Lex. In contrast to mAb SH1, anti-polymeric Lex mAbs make contact with the GlcNAc acetamido group, suggesting that epitopes extend further from the non-reducing end Lex. Results with SH2 show that this epitope is only recognized when DimLex is presented by glycoconjugates. We have reported that DimLex adopts two conformations around the β-d-GlcNAc-(1→3)-d-Gal bond connecting the Lex trisaccharides. We propose that only one of these conformations is recognized by SH2 and that this conformation is favored when the hexasaccharide is presented as part of a glycoconjugate such as DimLex-bovine serum albumin (DimLex-BSA). Proper presentation of the oligosaccharide candidate via conjugation to a protein or lipid is essential for the design of an anti-cancer vaccine or immunotherapeutic based on DimLex. Full article
(This article belongs to the Special Issue Carbohydrate Immunogens in Vaccines)
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Review
Electroporation as the Immunotherapy Strategy for Cancer in Veterinary Medicine: State of the Art in Latin America
Vaccines 2020, 8(3), 537; https://doi.org/10.3390/vaccines8030537 - 17 Sep 2020
Cited by 3 | Viewed by 1682
Abstract
Electroporation is a technology that increases cell membrane permeability by the application of electric pulses. Electrochemotherapy (ECT), the best-known application of electroporation, is a very effective local treatment for tumors of any histology in human and veterinary medicine. It induces a local yet [...] Read more.
Electroporation is a technology that increases cell membrane permeability by the application of electric pulses. Electrochemotherapy (ECT), the best-known application of electroporation, is a very effective local treatment for tumors of any histology in human and veterinary medicine. It induces a local yet robust immune response that is responsible for its high effectiveness. Gene electrotransfer (GET), used in research to produce a systemic immune response against cancer, is another electroporation-based treatment that is very appealing for its effectiveness, low cost, and simplicity. In this review, we present the immune effect of electroporation-based treatments and analyze the results of the vast majority of the published papers related to immune response enhancement by gene electrotransfer in companion animals with spontaneous tumors. In addition, we present a brief history of the initial steps and the state of the art of the electroporation-based treatments in Latin America. They have the potential to become an essential form of immunotherapy in the region. This review gives insight into the subject and helps to choose promising research lines for future work; it also helps to select the adequate treatment parameters for performing a successful application of this technology. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)
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Article
Effectiveness of a Simultaneous rHVT-F(ND) and rHVT-H5(AI) Vaccination of Day-Old Chickens and the Influence of NDV- and AIV-Specific MDA on Immune Response and Conferred Protection
Vaccines 2020, 8(3), 536; https://doi.org/10.3390/vaccines8030536 - 16 Sep 2020
Cited by 2 | Viewed by 952
Abstract
The recombinant herpesvirus of turkey (rHVT) vaccines targeting Newcastle disease (ND) and H5Nx avian influenza (AI) have been demonstrated efficient in chickens when used individually at day-old. Given the practical field constraints associated with administering two vaccines separately and in the absence of [...] Read more.
The recombinant herpesvirus of turkey (rHVT) vaccines targeting Newcastle disease (ND) and H5Nx avian influenza (AI) have been demonstrated efficient in chickens when used individually at day-old. Given the practical field constraints associated with administering two vaccines separately and in the absence of a currently available bivalent rHVT vector vaccine expressing both F(ND) and H5(AI) antigens, the aim of this study was to investigate whether interference occurs between the two vaccines when simultaneously administered in a single shot. The studies have been designed to determine (i) the ND and AI-specific protection and antibody response conferred by these vaccines inoculated alone or in combination at day-old, (ii) the influence of maternally-derived antibodies (MDA), and (iii) the potential interference between the two vaccine. Our results demonstrate that their combined administration is efficient to protect chickens against clinical signs of velogenic Newcastle disease virus (vNDV) and H5-highly pathogenic avian influenza virus (HPAIV) infections. Viral shedding following co-vaccination is also markedly reduced, while slightly lower NDV- and AIV-specific antibody responses are observed. NDV- and AIV-specific MDA show negative effects on the onset of the specific antibody responses. However, if AIV-specific MDA reduce the protection against H5-HPAIV induced by rHVT-H5(AI) vaccine, it was not observed for ND. Full article
(This article belongs to the Special Issue Poultry Vaccines)
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Article
Relationship between Influenza Vaccination Coverage Rate and COVID-19 Outbreak: An Italian Ecological Study
Vaccines 2020, 8(3), 535; https://doi.org/10.3390/vaccines8030535 - 16 Sep 2020
Cited by 29 | Viewed by 11482
Abstract
Background: The lack of specific vaccines or drugs against coronavirus disease 2019 (COVID-19) warrants studies focusing on alternative clinical approaches to reduce the spread of this pandemic disease. In this study, we investigated whether anti-influenza vaccination plays a role in minimizing the diffusion [...] Read more.
Background: The lack of specific vaccines or drugs against coronavirus disease 2019 (COVID-19) warrants studies focusing on alternative clinical approaches to reduce the spread of this pandemic disease. In this study, we investigated whether anti-influenza vaccination plays a role in minimizing the diffusion of COVID-19 in the Italian population aged 65 and over. Methods: Four COVID-19 outcomes were used: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, hospitalizations for COVID-19 symptoms, admissions to intensive care units for reasons related to SARS-CoV-2, and deaths attributable to COVID-19. Results: At univariate analyses, the influenza vaccination coverage rates correlated negatively with all COVID-19 outcomes (Beta ranging from −134 to −0.61; all p < 0.01). At multivariable analyses, influenza vaccination coverage rates correlated independently with SARS-CoV-2 seroprevalence (Beta (95% C.I.): −130 (−198, −62); p = 0.001), hospitalizations for COVID-19 symptoms (Beta (95% C.I.): −4.16 (−6.27, −2.05); p = 0.001), admission to intensive care units for reasons related to SARS-CoV-2 (Beta (95% C.I.): −0.58 (−1.05, −0.12); p = 0.017), and number of deaths attributable to COVID-19 (Beta (95% C.I.): −3.29 (−5.66, −0.93); p = 0.010). The R2 observed in the unadjusted analysis increased from 82% to 159% for all the considered outcomes after multivariable analyses. Conclusions: In the Italian population, the coverage rate of the influenza vaccination in people aged 65 and over is associated with a reduced spread and a less severe clinical expression of COVID-19. This finding warrants ad hoc studies to investigate the role of influenza vaccination in preventing the spread of COVID-19. Full article
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Review
Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects
Vaccines 2020, 8(3), 534; https://doi.org/10.3390/vaccines8030534 - 16 Sep 2020
Cited by 4 | Viewed by 1521
Abstract
In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, [...] Read more.
In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic. This review will provide an overview of the diverse range of vaccination techniques available to target the dermal compartment, as well as their current state, challenges, and prospects, and touch upon the formulations that have been developed to maximally benefit from these new techniques. These include needle and syringe techniques, microneedles, DNA tattooing, jet and ballistic delivery, and skin permeabilization techniques, including thermal ablation, chemical enhancers, ablation, electroporation, iontophoresis, and sonophoresis. Full article
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Article
Evaluation of Antibody Response Directed against Porcine Reproductive and Respiratory Syndrome Virus Structural Proteins
Vaccines 2020, 8(3), 533; https://doi.org/10.3390/vaccines8030533 - 16 Sep 2020
Viewed by 1067
Abstract
Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate [...] Read more.
Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of the kinetics of antibody appearance revealed that antibodies specific to N protein appeared earlier than antibodies against GP3. Finally, the assay was applied to measure immunoreactivities of clinical serum samples against N and GP3. The diagnostic sensitivity of the LIPS with N protein was superior to that of the LIPS with GP3. Collectively, the results provide additional information about the host antibody response to PRRSV infection. Full article
(This article belongs to the Special Issue PRRSV Vaccinology and Immunology)
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Article
Potent Protective Immune Responses to Senecavirus Induced by Virus-Like Particle Vaccine in Pigs
Vaccines 2020, 8(3), 532; https://doi.org/10.3390/vaccines8030532 - 15 Sep 2020
Cited by 1 | Viewed by 963
Abstract
Senecavirus A (SVA) is the pathogen that has recently caused porcine idiopathic vesicular disease (PIVD). The clinical symptoms of PIVD are similar to those of acute foot-and-mouth disease and also can result in the death of newborn piglets, thus entailing economic losses. Vaccine [...] Read more.
Senecavirus A (SVA) is the pathogen that has recently caused porcine idiopathic vesicular disease (PIVD). The clinical symptoms of PIVD are similar to those of acute foot-and-mouth disease and also can result in the death of newborn piglets, thus entailing economic losses. Vaccine immunization is the most effective way to prevent and control SVA. Among all SVA vaccines reported, only the SVA inactivated vaccine has been successfully developed. However, to ensure the elimination of this pathogen, safer and more effective vaccines are urgently required. A virus-like particles (VLPs)-based vaccine is probably the best alternative to inactivated vaccine. To develop an SVA VLPs vaccine and evaluate its immune effect, a prokaryotic expression system was used to produce SVA capsid protein and assemble VLPs. The VLPs were characterized by affinity chromatography, sucrose density gradient centrifugation, ZetaSizer and transmission electron microscopy. Meanwhile, the SVA CH-HB-2017 strain was used to infect pigs and to determine infection routes and dose. Experimental pigs were then immunized with the SVA VLPs vaccine emulsified in an ISA 201 adjuvant. The results showed that the VLPs vaccine induced neutralizing and specific antibodies at similar levels as an inactivated SVA vaccine after immunization. The level of INF-γ induced by the VLPs vaccine gradually decreased—similar to that of inactivated vaccine. These results indicated that VLPs vaccine may simultaneously cause both cellular and humoral immune responses. Importantly, after the challenge, the VLPs vaccine provided similar levels of protection as the inactivated SVA vaccine. In this study, we successfully obtained novel SVA VLPs and confirmed their highly immunogenicity, thus providing a superior candidate vaccine for defense and elimination of SVA, compared to the inactivated vaccine. Full article
(This article belongs to the Special Issue Controlled Clinical Evaluation of Veterinary Vaccines)
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Review
Current State of Global African Swine Fever Vaccine Development under the Prevalence and Transmission of ASF in China
Vaccines 2020, 8(3), 531; https://doi.org/10.3390/vaccines8030531 - 15 Sep 2020
Cited by 3 | Viewed by 2254
Abstract
African swine fever (ASF) is a highly lethal contagious disease of swine caused by African swine fever virus (ASFV). At present, it is listed as a notifiable disease reported to the World Organization for Animal Health (OIE) and a class one animal disease [...] Read more.
African swine fever (ASF) is a highly lethal contagious disease of swine caused by African swine fever virus (ASFV). At present, it is listed as a notifiable disease reported to the World Organization for Animal Health (OIE) and a class one animal disease ruled by Chinese government. ASF has brought significant economic losses to the pig industry since its outbreak in China in August 2018. In this review, we recapitulated the epidemic situation of ASF in China as of July 2020 and analyzed the influencing factors during its transmission. Since the situation facing the prevention, control, and eradication of ASF in China is not optimistic, safe and effective vaccines are urgently needed. In light of the continuous development of ASF vaccines in the world, the current scenarios and evolving trends of ASF vaccines are emphatically analyzed in the latter part of the review. The latest research outcomes showed that attempts on ASF gene-deleted vaccines and virus-vectored vaccines have proven to provide complete homologous protection with promising efficacy. Moreover, gaps and future research directions of ASF vaccine are also discussed. Full article
(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)
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Review
The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response
Vaccines 2020, 8(3), 530; https://doi.org/10.3390/vaccines8030530 - 14 Sep 2020
Cited by 3 | Viewed by 1385
Abstract
Zika Virus (ZIKV) and Dengue Virus (DENV) are related viruses of the Flavivirus genus that cause significant disease in humans. Existing control measures have been ineffective at curbing the increasing global incidence of infection for both viruses and they are therefore prime targets [...] Read more.
Zika Virus (ZIKV) and Dengue Virus (DENV) are related viruses of the Flavivirus genus that cause significant disease in humans. Existing control measures have been ineffective at curbing the increasing global incidence of infection for both viruses and they are therefore prime targets for new vaccination strategies. Type-I interferon (IFN) responses are important in clearing viral infection and for generating efficient adaptive immune responses towards infection and vaccination. However, ZIKV and DENV have evolved multiple molecular mechanisms to evade type-I IFN production. This review covers the molecular interactions, from detection to evasion, of these viruses with the type-I IFN response. Additionally, we discuss how this knowledge can be exploited to improve the design of new vaccine strategies. Full article
(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)
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Review
The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines
Vaccines 2020, 8(3), 529; https://doi.org/10.3390/vaccines8030529 - 14 Sep 2020
Cited by 2 | Viewed by 1648
Abstract
Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. [...] Read more.
Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Advances and Future Prospects)
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Article
Near-Infrared Photoimmunotherapy Combined with CTLA4 Checkpoint Blockade in Syngeneic Mouse Cancer Models
Vaccines 2020, 8(3), 528; https://doi.org/10.3390/vaccines8030528 - 14 Sep 2020
Cited by 5 | Viewed by 1155
Abstract
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that induces necrotic/immunogenic cell death. It employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by NIR light. Tumor-targeting NIR-PIT is also at least partly [...] Read more.
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that induces necrotic/immunogenic cell death. It employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by NIR light. Tumor-targeting NIR-PIT is also at least partly mediated by a profound immune response against the tumor. Cytotoxic T-lymphocyte antigen-4 (CTLA4) is widely recognized as a major immune checkpoint protein, which inhibits the immune response against tumors and is therefore, a target for systemic blockade. We investigated the effect of combining tumor-targeted NIR-PIT against the cell-surface antigen, CD44, which is known as a cancer stem cell marker, with a systemic CTLA4 immune checkpoint inhibitor in three syngeneic tumor models (MC38-luc, LL/2, and MOC1). CD44-targeted NIR-PIT combined with CTLA4 blockade showed greater tumor growth inhibition with longer survival compared with CTLA4 blockade alone in all tumor models. NIR-PIT and CTLA4 blockade produced more complete remission in MOC1 tumors (44%) than NIR-PIT and programmed cell death protein 1 (PD-1) blockade (8%), which was reported in our previous paper. However, the combination of NIR-PIT and CTLA4 blockade was less effective in MC38-luc tumors (11%) than the combination of NIR-PIT and PD-1 blockade (70%). Nonetheless, in many cases ineffective results with NIR-PIT and PD-1 blockade were reversed with NIR-PIT and CTLA4 blockade. Full article
(This article belongs to the Section Cellular/Molecular Immunology)
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Article
Behavioral Differences in the Preference for Hepatitis B Virus Vaccination: A Discrete Choice Experiment
Vaccines 2020, 8(3), 527; https://doi.org/10.3390/vaccines8030527 - 14 Sep 2020
Cited by 1 | Viewed by 1183
Abstract
Understanding behavioral factors differences in the preferences for vaccinations can improve predictions of vaccine uptake rates and identify effective policy interventions to increase the demand for vaccinations. In this study, 353 adults in Shandong province in China were interviewed about their preferences for [...] Read more.
Understanding behavioral factors differences in the preferences for vaccinations can improve predictions of vaccine uptake rates and identify effective policy interventions to increase the demand for vaccinations. In this study, 353 adults in Shandong province in China were interviewed about their preferences for hepatitis B virus (HBV) vaccination. A discrete choice experiment (DCE) was employed to analyze the preference for HBV vaccinations, and a mixed logit model was used to estimate respondent preferences for vaccination attributes included in the DCE. While the protection rate against hepatitis B (HB), duration of protection, risk of side-effects, and vaccination cost were shown to influence adults’ preferences for HBV vaccination, adults valued “99% hepatitis B protection” above other attributes, followed by “20 years’ protection duration” and “1 in 150,000 risk of side-effects”. Individuals with lower time discount rates, non-overconfidence, or higher risk aversion were more likely to choose a vaccine. Lower risk aversion individuals showed a higher preference for lower risk of side-effects. Lower time discount rate individuals showed a higher preference for longer protection duration. Non-overconfidence individuals showed a higher preference for higher hepatitis B protection and cost. Interventions should be targeted to the behavioral determinants impeding vaccination. Full article
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