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Vaccines, Volume 7, Issue 3 (September 2019)

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Open AccessArticle
Reduction in Oviposition of Poultry Red Mite (Dermanyssus gallinae) in Hens Vaccinated with Recombinant Akirin
Vaccines 2019, 7(3), 121; https://doi.org/10.3390/vaccines7030121 (registering DOI) - 19 Sep 2019
Abstract
The poultry red mite (PRM), Dermanyssus gallinae, is a hematophagous ectoparasite of birds with worldwide distribution that causes economic losses in the egg-production sector of the poultry industry. Traditional control methods, mainly based on acaricides, have been only partially successful, and new [...] Read more.
The poultry red mite (PRM), Dermanyssus gallinae, is a hematophagous ectoparasite of birds with worldwide distribution that causes economic losses in the egg-production sector of the poultry industry. Traditional control methods, mainly based on acaricides, have been only partially successful, and new vaccine-based interventions are required for the control of PRM. Vaccination with insect Akirin (AKR) and its homolog in ticks, Subolesin (SUB), have shown protective efficacy for the control of ectoparasite infestations and pathogen infection/transmission. The aim of this study was the identification of the akr gene from D. gallinae (Deg-akr), the production of the recombinant Deg-AKR protein, and evaluation of its efficacy as a vaccine candidate for the control of PRM. The anti-Deg-AKR serum IgY antibodies in hen sera and egg yolk were higher in vaccinated than control animals throughout the experiment. The results demonstrated the efficacy of the vaccination with Deg-AKR for the control of PRM by reducing mite oviposition by 42% following feeding on vaccinated hens. A negative correlation between the levels of serum anti-Deg-AKR IgY and mite oviposition was obtained. These results support Deg-AKR as a candidate protective antigen for the control of PRM population growth. Full article
(This article belongs to the Special Issue Arthropod Ectoparasites and Associated Diseases)
Open AccessArticle
In Vivo Administration of Recombinant Human Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination
Vaccines 2019, 7(3), 120; https://doi.org/10.3390/vaccines7030120 (registering DOI) - 19 Sep 2019
Abstract
Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in [...] Read more.
Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity. Full article
(This article belongs to the Section Cancer Vaccines and Immunotheraphy)
Open AccessReview
Viral Vectors for the Induction of Broadly Neutralizing Antibodies against HIV
Vaccines 2019, 7(3), 119; https://doi.org/10.3390/vaccines7030119 (registering DOI) - 19 Sep 2019
Abstract
Extensive research on generating an efficient HIV vaccine is ongoing. A major aim of HIV vaccines is the induction of long-lasting, broadly neutralizing antibodies (bnAbs) that can confer sterile immunity for a prolonged period of time. Several strategies have been explored to reach [...] Read more.
Extensive research on generating an efficient HIV vaccine is ongoing. A major aim of HIV vaccines is the induction of long-lasting, broadly neutralizing antibodies (bnAbs) that can confer sterile immunity for a prolonged period of time. Several strategies have been explored to reach this goal, i.e. protein immunization, DNA, or viral vectors, or a combination thereof. In this review, we give an overview of approaches using viral vectors for the induction of HIV-specific bnAbs. Many pre-clinical studies were performed using various replication-competent and -incompetent vectors. Amongst them, poxviral and adenoviral vectors were the most prevalent ones. In many studies, viral vectors were combined with a DNA prime or a protein boost. However, neutralizing antibodies were mainly induced against the homologous HIV-1 vaccine strain or tier 1 viruses, and in rare cases, against tier 2 viruses, indicating the need for improved antigens and vaccination strategies. Furthermore, we also review next generation Env antigens that are currently being used in protein vaccination approaches and point out how they could be utilized in viral vectors. Full article
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
Open AccessCommunication
A Survey of Vaccine-Induced Measles IgG Antibody Titer to Verify Temporal Changes in Response to Measles Vaccination in Young Adults
Vaccines 2019, 7(3), 118; https://doi.org/10.3390/vaccines7030118 (registering DOI) - 19 Sep 2019
Abstract
In Japan, sporadic measles cases increased rapidly in 2019 compared to the past six years. To clarify the persistence of immunity against measles in young adults, this study explored the persistence of immunoglobulin G (IgG) antibody titers against the measles virus in 17- [...] Read more.
In Japan, sporadic measles cases increased rapidly in 2019 compared to the past six years. To clarify the persistence of immunity against measles in young adults, this study explored the persistence of immunoglobulin G (IgG) antibody titers against the measles virus in 17- to 24-year-old young participants who reside in the Chiba prefecture of Japan. Measles-specific IgG antibody titers, determined by enzyme immunoassay in serum samples collected from 506 participants, were assessed through statistical analyses. Multivariable regression analysis revealed that the distribution of measles IgG antibody titers was significantly correlated with a medical history of measles (P < 0.05), while there was no significant correlation between the number of vaccinations related to measles IgG titers. Furthermore, measles IgG titers tended to decrease, as revealed by the temporal change in IgG titers, during the elapsed period after the last vaccination (P = 0.08). These results indicate that periodic vaccination against measles is required to prevent sporadic measles infection in young and older adults. Full article
(This article belongs to the Section Epidemiology)
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Open AccessArticle
An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains
Vaccines 2019, 7(3), 117; https://doi.org/10.3390/vaccines7030117 - 18 Sep 2019
Viewed by 126
Abstract
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel [...] Read more.
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and other Viruses)
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Open AccessReview
Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential forContraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision
Vaccines 2019, 7(3), 116; https://doi.org/10.3390/vaccines7030116 - 16 Sep 2019
Viewed by 201
Abstract
Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in [...] Read more.
Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9–12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However, ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility; and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involving ASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing. Full article
Open AccessArticle
Immunological Analysis of a CCHFV mRNA Vaccine Candidate in Mouse Models
Vaccines 2019, 7(3), 115; https://doi.org/10.3390/vaccines7030115 - 16 Sep 2019
Viewed by 169
Abstract
Development of new vaccine platforms against viral diseases is considered urgent. In recent years, mRNA constructs have attracted great interest in this field due to unique advantages over conventional gene transfer platforms. In the present study, we developed a new naked conventional mRNA [...] Read more.
Development of new vaccine platforms against viral diseases is considered urgent. In recent years, mRNA constructs have attracted great interest in this field due to unique advantages over conventional gene transfer platforms. In the present study, we developed a new naked conventional mRNA vaccine expressing the non-optimized small (S) segment of the Ank-2 strain of Crimean-Congo Hemorrhagic Fever virus (CCHFV). We then analyzed its single and booster dose immunogenicity and protection potential in the challenge assay in two mice models, including IFNα/β/γR−/− and C57BL/6. The results obtained from the immunological assays, namely IL-4 and IFN-gamma ELISPOT, intracellular IFN-gamma staining, in-house sandwich ELISA, and survival data, demonstrated that our construct elicited the production of anti-nucleocapsid (N) specific immune responses in both mice models. A 100% protection rate was only obtained in the booster dose group of IFNα/β/γR−/− mice, indicating that this platform needs further optimization in future studies. In conclusion, we assessed a novel approach in CCHFV vaccination by introducing a conventional mRNA platform which can be considered in future experiments as an efficient and safe way to battle this disease. Full article
(This article belongs to the Special Issue RNA Vaccines)
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Open AccessArticle
Tick Bites Induce Anti-α-Gal Antibodies in Dogs
Vaccines 2019, 7(3), 114; https://doi.org/10.3390/vaccines7030114 - 15 Sep 2019
Viewed by 270
Abstract
Due to the functional inactivation of the gene encoding for the enzyme that is involved in the oligosaccharide galactose-α-1,3-galactose (α-Gal) synthesis, humans and Old-World primates are able to produce a large amount of antibodies against the glycan epitope. Apart from being involved in [...] Read more.
Due to the functional inactivation of the gene encoding for the enzyme that is involved in the oligosaccharide galactose-α-1,3-galactose (α-Gal) synthesis, humans and Old-World primates are able to produce a large amount of antibodies against the glycan epitope. Apart from being involved in the hyperacute organ rejection in humans, anti-α-Gal antibodies have shown a protective effect against some pathogenic agents and an implication in the recently recognized tick-induced mammalian meat allergy. Conversely, non-primate mammals, including dogs, have the ability to synthetize α-Gal and, thus, their immune system is not expected to naturally generate the antibodies toward this self-antigen molecule. However, in the current study, we detected specific IgG, IgM, and IgE antibodies to α-Gal in sera of clinically healthy dogs by an indirect enzyme-linked immunosorbent assay (ELISA) for the first time. Furthermore, in a tick infestation experiment, we showed that bites of Ixodes ricinus induce the immune response to α-Gal in dogs and that the resulting antibodies (IgM) might be protective against Anaplasma phagocytophilum. These findings may help lead to a better understanding of the underlying mechanisms involved in mammalian meat allergy and tick-host-pathogen interactions, but they also open up the question about the possibility that dogs could develop an allergy to mammalian meat after tick bites, similar to that in humans. Full article
(This article belongs to the Special Issue Arthropod Ectoparasites and Associated Diseases)
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Open AccessArticle
TIV Vaccination Modulates Host Responses to Influenza Virus Infection that Correlate with Protection against Bacterial Superinfection
Vaccines 2019, 7(3), 113; https://doi.org/10.3390/vaccines7030113 - 12 Sep 2019
Viewed by 214
Abstract
Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the [...] Read more.
Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the effect of suboptimal vaccination on the outcome of post-influenza bacterial superinfection. Methods: We established a mouse vaccination model that allows control of disease severity after influenza virus infection despite inefficient induction of virus-neutralizing antibody titers by vaccination. We investigated the effect of vaccination on virus-induced host immune responses and on the outcome of superinfection with Staphylococcus aureus. Results: Vaccination with trivalent inactivated virus vaccine (TIV) reduced morbidity after influenza A virus infection but did not prevent virus replication completely. Despite the poor induction of influenza-specific antibodies, TIV protected from mortality after bacterial superinfection. Vaccination limited loss of alveolar macrophages and reduced levels of infiltrating pulmonary monocytes after influenza virus infection. Interestingly, TIV vaccination resulted in enhanced levels of eosinophils after influenza virus infection and recruitment of neutrophils in both lungs and mediastinal lymph nodes after bacterial superinfection. Conclusion: These observations highlight the importance of disease modulation by influenza vaccination, even when suboptimal, and suggest that influenza vaccination is still beneficial to protect during bacterial superinfection in the absence of complete virus neutralization. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
Open AccessArticle
An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model
Vaccines 2019, 7(3), 112; https://doi.org/10.3390/vaccines7030112 - 12 Sep 2019
Viewed by 179
Abstract
Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we [...] Read more.
Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate. Full article
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Open AccessArticle
Mutations in VP0 and 2C Proteins of Duck Hepatitis A Virus Type 3 Attenuate Viral Infection and Virulence
Vaccines 2019, 7(3), 111; https://doi.org/10.3390/vaccines7030111 - 11 Sep 2019
Viewed by 360
Abstract
Duck hepatitis A virus (DHAV) is prevalent worldwide and has caused significant economic losses. As the predominant serotype in China, DHAV-3 has become a major challenge to the local duck industry. Here the genetics and pathogenesis of a virulent DHAV-3 strain and its [...] Read more.
Duck hepatitis A virus (DHAV) is prevalent worldwide and has caused significant economic losses. As the predominant serotype in China, DHAV-3 has become a major challenge to the local duck industry. Here the genetics and pathogenesis of a virulent DHAV-3 strain and its embryo-passaged strain were assessed. There were only two amino acid substitutions (Y164N in VP0 protein and L71I in 2C protein) introduced during the adaptation process. The pathogenicity of these strains was further evaluated in vivo. Clinical signs, gross pathology, and histopathological analysis showed that the embryo-passaged strain was attenuated. Meanwhile, the viral RNA loads were significantly lower in the liver tissues of the ducklings infected with the attenuated strain. As expected, infection with the virulent and attenuated strains led to the activation of different innate immune genes. We suspected that the loss of replication efficiency in ducklings was responsible for the attenuation phenotype of the embryo-passaged strain. In addition, different innate immune responses in the liver of ducklings were at least partly responsible for the differential infectivity phenotype. These findings provide new insights into the genetics and pathogenesis of DHAV-3, which may aid the development of new vaccines and the implementation of immunization strategies. Full article
(This article belongs to the Section Veterinary Vaccines)
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Open AccessReview
The Cellular Immune Response to Rabies Vaccination: A Systematic Review
Vaccines 2019, 7(3), 110; https://doi.org/10.3390/vaccines7030110 - 11 Sep 2019
Viewed by 279
Abstract
The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on [...] Read more.
The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on the kinetics and composition of the cellular immune response to rabies vaccination in humans. A total of 1360 studies were identified in an extensive literature search. Twenty studies were selected for inclusion. In a primary response, plasma cells are detectable from day 7 to day 14, peaking at day 10. Memory B-cells appear from day 10 up to at least day 28. After revaccination, natural killer (NK) cells are the first detectable cellular parameters. Further research is required to assess cellular parameters in relation to long-term (serological) immunity. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42019134416. Full article
Open AccessArticle
Investigation of the Effect of PD-L1 Blockade on Triple Negative Breast Cancer Cells Using Fourier Transform Infrared Spectroscopy
Vaccines 2019, 7(3), 109; https://doi.org/10.3390/vaccines7030109 - 09 Sep 2019
Viewed by 313
Abstract
Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In [...] Read more.
Interactions between programmed death-1 (PD-1) with its ligand PD-L1 on tumor cells can antagonize T cell responses. Inhibiting these interactions using immune checkpoint inhibitors has shown promise in cancer immunotherapy. MDA-MB-231 is a triple negative breast cancer cell line that expresses PD-L1. In this study, we investigated the biochemical changes in MDA-MB-231 cells following treatment with atezolizumab, a specific PD-L1 blocker. Our readouts were Fourier Transform Infrared (FTIR) spectroscopy and flow cytometric analyses. Chemometrical analysis, such as principal component analysis (PCA), was applied to delineate the spectral differences. We were able to identify the chemical alterations in both protein and lipid structure of the treated cells. We found that there was a shift from random coil and α-helical structure to β-sheet conformation of PD-L1 on tumor cells due to atezolizumab treatment, which could hinder binding with its receptors on immune cells, ensuring sustained T cell activation for potent immune responses. This work provides novel information about the effects of atezolizumab at molecular and cellular levels. FTIR bio-spectroscopy, in combination with chemometric analyses, may expedite research and offer new approaches for cancer immunology. Full article
(This article belongs to the Section Cancer Vaccines and Immunotheraphy)
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Open AccessArticle
A Novel Integrated and Labile eHealth System for Monitoring Dog Rabies Vaccination Campaigns
Vaccines 2019, 7(3), 108; https://doi.org/10.3390/vaccines7030108 - 09 Sep 2019
Viewed by 310
Abstract
The elimination of canine rabies through the implementation of high coverage mass dog vaccination campaigns is a complex task, particularly in the resource-limited countries of the rabies endemic world. Here we demonstrated the feasibility of applying targeted rabies vaccination campaigns to deliver more [...] Read more.
The elimination of canine rabies through the implementation of high coverage mass dog vaccination campaigns is a complex task, particularly in the resource-limited countries of the rabies endemic world. Here we demonstrated the feasibility of applying targeted rabies vaccination campaigns to deliver more impactful intervention campaigns in resource-limited settings using evidence and lessons learnt from other diseases. With the use of strategic rabies intervention programs, we demonstrate the noteworthy reduction of rabies cases in two very different African settings. The strategic intervention was most significantly aided by the use of a custom-developed vaccination tracking device (the Global Alliance for Rabies Control (GARC) Data Logger) and an integrated rabies surveillance system (the Rabies Epidemiological Bulletin). Our first case study, an island-wide strategic dog vaccination on Tanzania’s Unguja island, reduced the incidence of rabies by 71% in the first 16 months of implementation. In the second case study, a similar approach was applied in the metropolitan capital city of Zimbabwe and the incidence of rabies declined by 13% during the first 13 months of implementation. The methodologies and results presented here suggest that, in resource-limited settings, an optimal approach towards the elimination of dog rabies would revolve around strategic interventions, subject to the use of appropriate planning, surveillance, and vaccination tools. Full article
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Open AccessCommentary
Original Antigenic Sin and Respiratory Syncytial Virus Vaccines
Vaccines 2019, 7(3), 107; https://doi.org/10.3390/vaccines7030107 - 06 Sep 2019
Viewed by 329
Abstract
The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure [...] Read more.
The original antigenic sin (OAS) theory considers the outcome of the first encounter with an antigen. It favors a memory response to the original antigen upon exposure to a similar or related antigen, and includes both positive and negative impacts of past exposure on the memory response to challenge, and, in particular, on vaccine efficacy. This phenomenon is closely linked with imprinting and the hierarchical nature of immune responses to previously encountered antigens. The focus of this commentary centers on the potential role of OAS or immunological imprinting on respiratory syncytial virus memory responses. Full article
(This article belongs to the Special Issue Pathobiology of Respiratory Syncytial Virus (RSV))
Open AccessArticle
Immunomodulatory Potential of Tinospora cordifolia and CpG ODN (TLR21 Agonist) against the Very Virulent, Infectious Bursal Disease Virus in SPF Chicks
Vaccines 2019, 7(3), 106; https://doi.org/10.3390/vaccines7030106 - 04 Sep 2019
Viewed by 318
Abstract
Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is characterized by severe immunosuppression in young chicks of 3 to 6 week age group. Although vaccines are available to prevent IBD, outbreaks of disease are still noticed in the field among [...] Read more.
Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is characterized by severe immunosuppression in young chicks of 3 to 6 week age group. Although vaccines are available to prevent IBD, outbreaks of disease are still noticed in the field among vaccinated flocks. Further, the birds surviving IBD become susceptible to secondary infections caused by various viral and bacterial agents. This study assessed the immunoprophylactic potential of Cytosine-guanosinedeoxynucleotide (CpG) oligodeoxynucleotides (ODN) and Tinospora cordifolia stem aqueous extract in the specific pathogen free (SPF) chicks, experimentally infected with very virulent IBDV (vvIBDV). Both of these agents (CpG ODN and herbal extract) showed significant increase in the IFN-γ, IL-2, IL-4, and IL-1 levels in the peripheral blood mononuclear cells (PBMCs) (p < 0.05) of chickens in the treatment groups following IBD infection. Further we found significant reduction in mortality rate in vvIBDV infected chicks treated with either, or in combination, compared with the birds of control group. Additionally, the adjuvant or immune enhancing potential of these two immunomodulatory agents with the commercially available IBDV vaccine was determined in chicks. The augmentation of vaccine response in terms of an enhanced antibody titer after vaccination, along with either or a combination of the two agents was noticed. The findings provide a way forward to counter the menace of IBDV in the poultry sector through use of these herbal or synthetic immunomodulatory supplements. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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Open AccessReview
Peptide-Based Vaccination for Antibody Responses Against HIV
Vaccines 2019, 7(3), 105; https://doi.org/10.3390/vaccines7030105 - 02 Sep 2019
Viewed by 433
Abstract
HIV-1 is responsible for a global pandemic of 35 million people and continues to spread at a rate of >2 million new infections/year. It is widely acknowledged that a protective vaccine would be the most effective means to reduce HIV-1 spread and ultimately [...] Read more.
HIV-1 is responsible for a global pandemic of 35 million people and continues to spread at a rate of >2 million new infections/year. It is widely acknowledged that a protective vaccine would be the most effective means to reduce HIV-1 spread and ultimately eliminate the pandemic, whereas a therapeutic vaccine might help to mitigate the clinical course of the disease and to contribute to virus eradication strategies. However, despite more than 30 years of research, we do not have a vaccine capable of protecting against HIV-1 infection or impacting on disease progression. This, in part, denotes the challenge of identifying immunogens and vaccine modalities with a reduced risk of failure in late stage development. However, progress has been made in epitope identification for the induction of broadly neutralizing antibodies. Thus, peptide-based vaccination has become one of the challenges of this decade. While some researchers reconstitute envelope protein conformation and stabilization to conserve the epitope targeted by neutralizing antibodies, others have developed strategies based on peptide-carrier vaccines with a similar goal. Here, we will review the major peptide-carrier based approaches in the vaccine field and their application and recent development in the HIV-1 field. Full article
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
Open AccessConcept Paper
Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine
Vaccines 2019, 7(3), 104; https://doi.org/10.3390/vaccines7030104 - 01 Sep 2019
Viewed by 356
Abstract
Infections with the human cytomegalovirus (HCMV) are associated with severe clinical manifestations in children following prenatal transmission and after viral reactivation in immunosuppressed individuals. The development of an HCMV vaccine has long been requested but there is still no licensed product available. Subviral [...] Read more.
Infections with the human cytomegalovirus (HCMV) are associated with severe clinical manifestations in children following prenatal transmission and after viral reactivation in immunosuppressed individuals. The development of an HCMV vaccine has long been requested but there is still no licensed product available. Subviral dense bodies (DB) are immunogenic in pre-clinical models and are thus a promising HCMV vaccine candidate. Recently, we established a virus based on the laboratory strain Towne that synthesizes large numbers of DB containing the pentameric protein complex gH/gL/UL128-131 (Towne-UL130repΔGFP). The work presented here focuses on providing strategies for the production of a safe vaccine based on that strain. A GMP-compliant protocol for DB production was established. Furthermore, the DB producer strain Towne-UL130rep was attenuated by deleting the UL25 open reading frame. Additional genetic modifications aim to abrogate its capacity to replicate in vivo by conditionally expressing pUL51 using the Shield-1/FKBP destabilization system. We further show that the terminase inhibitor letermovir can be used to reduce infectious virus contamination of a DB vaccine by more than two orders of magnitude. Taken together, strategies are provided here that allow for the production of a safe and immunogenic DB vaccine for clinical testing. Full article
(This article belongs to the Special Issue Cytomegalovirus Infection and Vaccine Development)
Open AccessReview
Understudied Factors Influencing Fc-Mediated Immune Responses against Viral Infections
Vaccines 2019, 7(3), 103; https://doi.org/10.3390/vaccines7030103 - 30 Aug 2019
Viewed by 379
Abstract
Antibodies play a crucial role in host defense against viruses, both by preventing infection and by controlling viral replication. Besides their capacity to neutralize viruses, antibodies also exert their antiviral effects by crystallizable fragment (Fc)-mediated effector mechanisms. This involves a bridge between innate [...] Read more.
Antibodies play a crucial role in host defense against viruses, both by preventing infection and by controlling viral replication. Besides their capacity to neutralize viruses, antibodies also exert their antiviral effects by crystallizable fragment (Fc)-mediated effector mechanisms. This involves a bridge between innate and adaptive immune systems, wherein antibodies form immune complexes that drive numerous innate immune effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent complement-mediated lysis, and antibody-dependent phagocytosis. Here, we review certain mechanisms that modulate these antibody-mediated effector functions against virally infected cells, such as viral glycoprotein shedding, viral glycoprotein internalization, antibody cooperativity, and antibody glycosylation. These mechanisms can either protect viral replication or enhance infected cell clearance. Here we discuss the importance of these understudied factors in modulating Fc-mediated effector functions. Full article
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
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Open AccessReview
The Role of Extracellular Vesicles in Viral Infection and Transmission
Vaccines 2019, 7(3), 102; https://doi.org/10.3390/vaccines7030102 - 28 Aug 2019
Viewed by 575
Abstract
Extracellular vesicles (EVs) have been found to be released by any type of cell and can be retrieved in every circulating body fluid, namely blood (plasma, serum), saliva, milk, and urine. EVs were initially considered a cellular garbage disposal tool, but later it [...] Read more.
Extracellular vesicles (EVs) have been found to be released by any type of cell and can be retrieved in every circulating body fluid, namely blood (plasma, serum), saliva, milk, and urine. EVs were initially considered a cellular garbage disposal tool, but later it became evident that they are involved in intercellular signaling. There is evidence that viruses can use EV endocytic routes to enter uninfected cells and hijack the EV secretory pathway to exit infected cells, thus illustrating that EVs and viruses share common cell entry and biogenesis mechanisms. Moreover, EVs play a role in immune response against viral pathogens. EVs incorporate and spread both viral and host factors, thereby prompting or inhibiting immune responses towards them via a multiplicity of mechanisms. The involvement of EVs in immune responses, and their potential use as agents modulating viral infection, will be examined. Although further studies are needed, the engineering of EVs could package viral elements or host factors selected for their immunostimulatory properties, to be used as vaccines or tolerogenic tools in autoimmune diseases. Full article
(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)
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Open AccessArticle
A Convenient Synthetic Method to Improve Immunogenicity of Mycobacterium tuberculosis Related T-Cell Epitope Peptides
Vaccines 2019, 7(3), 101; https://doi.org/10.3390/vaccines7030101 - 27 Aug 2019
Viewed by 494
Abstract
Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely [...] Read more.
Epitopes from different proteins expressed by Mycobacterium tuberculosis (Rv1886c, Rv0341, Rv3873) were selected based on previously reported antigenic properties. Relatively short linear T-cell epitope peptides generally have unordered structure, limited immunogenicity, and low in vivo stability. Therefore, they rely on proper formulation and on the addition of adjuvants. Here we report a convenient synthetic route to induce a more potent immune response by the formation of a trivalent conjugate in spatial arrangement. Chemical and structural characterization of the vaccine conjugates was followed by the study of cellular uptake and localization. Immune response was assayed by the measurement of splenocyte proliferation and cytokine production, while vaccine efficacy was studied in a murine model of tuberculosis. The conjugate showed higher tendency to fold and increased internalization rate into professional antigen presenting cells compared to free epitopes. Cellular uptake was further improved by the incorporation of a palmitoyl group to the conjugate and the resulted pal-A(P)I derivative possessed an internalization rate 10 times higher than the free epitope peptides. Vaccination of CB6F1 mice with free peptides resulted in low T-cell response. In contrast, significantly higher T-cell proliferation with prominent expression of IFN-γ, IL-2, and IL-10 cytokines was measured for the palmitoylated conjugate. Furthermore, the pal-A(P)I conjugate showed relevant vaccine efficacy against Mycobacterium tuberculosis infection. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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Open AccessReview
Anti-Tat Immunity in HIV-1 Infection: Effects of Naturally Occurring and Vaccine-Induced Antibodies Against Tat on the Course of the Disease
Vaccines 2019, 7(3), 99; https://doi.org/10.3390/vaccines7030099 - 26 Aug 2019
Viewed by 669
Abstract
HIV-1 Tat is an essential protein in the virus life cycle, which is required for virus gene expression and replication. Most Tat that is produced during infection is released extracellularly and it plays a key role in HIV pathogenesis, including residual disease upon [...] Read more.
HIV-1 Tat is an essential protein in the virus life cycle, which is required for virus gene expression and replication. Most Tat that is produced during infection is released extracellularly and it plays a key role in HIV pathogenesis, including residual disease upon combination antiretroviral therapy (cART). Here, we review epidemiological and experimental evidence showing that antibodies against HIV-1 Tat, infrequently occurring in natural infection, play a protective role against disease progression, and that vaccine targeting Tat can intensify cART. In fact, Tat vaccination of subjects on suppressive cART in Italy and South Africa promoted immune restoration, including CD4+ T-cell increase in low immunological responders, and a reduction of proviral DNA even after six years of cART, when both CD4+ T-cell gain and DNA decay have reached a plateau. Of note, DNA decay was predicted by the neutralization of Tat-mediated entry of Env into dendritic cells by anti-Tat antibodies, which were cross-clade binding and neutralizing. Anti-Tat cellular immunity also contributed to the DNA decay. Based on these data, we propose the Tat therapeutic vaccine as a pathogenesis-driven intervention that effectively intensifies cART and it may lead to a functional cure, providing new perspectives and opportunities also for prevention and virus eradication strategies. Full article
(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)
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Open AccessArticle
Dog Ecology, Bite Incidence, and Disease Awareness: A Cross-Sectional Survey among a Rabies-Affected Community in the Democratic Republic of the Congo
Vaccines 2019, 7(3), 98; https://doi.org/10.3390/vaccines7030098 - 26 Aug 2019
Viewed by 628
Abstract
Despite the existence of safe and efficacious human and animal rabies vaccines, millions of people remain at risk of exposure to this deadly zoonotic disease through bites of infected dogs. Sub-Saharan African countries, such as the Democratic Republic of the Congo (DRC), bear [...] Read more.
Despite the existence of safe and efficacious human and animal rabies vaccines, millions of people remain at risk of exposure to this deadly zoonotic disease through bites of infected dogs. Sub-Saharan African countries, such as the Democratic Republic of the Congo (DRC), bear the highest per capita death rates from rabies where dog vaccination and availability of lifesaving post-exposure prophylaxis (PEP) is scarce. Mass dog vaccination is the most cost-effective and sustainable approach to prevent human rabies deaths. We conducted a cross-sectional household survey in a rabies-affected community in Matadi, DRC, to estimate the size of the owned dog population and dog bite incidence and assess knowledge and practices regarding rabies, as preparation for future mass dog vaccination campaigns. Our study revealed that the owned dog population in Matadi was almost ten times larger than assumed by local veterinary officials, with a large proportion of free-roaming unvaccinated dogs. The annual dog bite incidence of 5.2 per 1000 person years was high, whereas community rabies knowledge was low resulting in poor practices. Given these findings, human rabies deaths are likely to occur in this community. Lack of disease awareness could negatively affect participation in future mass dog vaccination campaigns. A public sensitization campaign is needed to promote appropriate rabies prevention (washing bite wounds and PEP) and control (dog vaccination) measures in this community. Full article
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Open AccessReview
Radiation as an In Situ Auto-Vaccination: Current Perspectives and Challenges
Vaccines 2019, 7(3), 100; https://doi.org/10.3390/vaccines7030100 - 26 Aug 2019
Viewed by 540
Abstract
Radiotherapy is generally considered to be a local treatment, but there have been reports of rare cases demonstrating abscopal effects in which antitumor effects have been observed in cancer lesions other than the irradiated site. This result is more likely to occur when [...] Read more.
Radiotherapy is generally considered to be a local treatment, but there have been reports of rare cases demonstrating abscopal effects in which antitumor effects have been observed in cancer lesions other than the irradiated site. This result is more likely to occur when immune checkpoint inhibitors are used in addition to radiotherapy. Certain radiation-induced chemokines and cytokines have immune-enhancing effects. Immune checkpoint inhibitors may strengthen these effects by stimulating antigen-presenting cells and effector cytotoxic T cells. To date, there is no consensus regarding the applicability of the abscopal effect in the clinical setting, including optimal methods for combining immune checkpoint inhibitors and irradiation. In this review, we highlight the evidence for interactions between cancer immunotherapy and radiotherapy and discuss the potential of such interactions for use in designing novel combination therapies. Full article
(This article belongs to the Section Cancer Vaccines and Immunotheraphy)
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Open AccessArticle
Procurement of Category 2 Vaccines in China
Vaccines 2019, 7(3), 97; https://doi.org/10.3390/vaccines7030097 - 23 Aug 2019
Viewed by 388
Abstract
Internationally, vaccine pricing is relatively opaque, although many low- or lower-middle-income countries belong to international consortiums that jointly procure vaccines. China procures vaccines domestically, and vaccines that require payment from the public (“category 2 vaccines”), have undergone several regulatory changes over the past [...] Read more.
Internationally, vaccine pricing is relatively opaque, although many low- or lower-middle-income countries belong to international consortiums that jointly procure vaccines. China procures vaccines domestically, and vaccines that require payment from the public (“category 2 vaccines”), have undergone several regulatory changes over the past 15 years. This study aims to describe the vaccine procurement method changes in China since 2005 and to analyze how the procurement method impacted vaccine price. This review of vaccine procurement reforms found that a shift to provincial-level Group Purchasing Organizations after 2016 was accompanied by an increase in most prices. There was more variability in vaccine prices across provinces for vaccines with only one supplier, and these vaccines have a higher price than what is found in United Nations Children’s Fund (UNICEF)-supported countries. China’s current procurement system for non-mandatory vaccines leaves these vaccines costing several-fold more than in other countries, and in particular those supported by Gavi, the Vaccine Alliance. Exploring a variety of methods to reduce vaccine purchase prices will not only directly benefit the general population, but also the government, as they aim to implement more programs to benefit public health in a cost-effective manner. Full article
(This article belongs to the Section Vaccines and Society)
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Open AccessArticle
Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine
Vaccines 2019, 7(3), 96; https://doi.org/10.3390/vaccines7030096 - 23 Aug 2019
Viewed by 537
Abstract
To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane [...] Read more.
To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-β+/Δβ-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity. Full article
(This article belongs to the Special Issue Immunization by Electroporation)
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Open AccessArticle
Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters
Vaccines 2019, 7(3), 95; https://doi.org/10.3390/vaccines7030095 - 22 Aug 2019
Viewed by 462
Abstract
Subunit vaccines conferring complete protection against leptospirosis are not currently available. The interactions of factor H binding proteins (FHBPs) on pathogenic leptospires and host factor H are crucial for immune evasion by inhibition of complement-mediated killing. The inhibition of these interactions may be [...] Read more.
Subunit vaccines conferring complete protection against leptospirosis are not currently available. The interactions of factor H binding proteins (FHBPs) on pathogenic leptospires and host factor H are crucial for immune evasion by inhibition of complement-mediated killing. The inhibition of these interactions may be a potential strategy to clear leptospires in the host. This study aimed to evaluate a multisubunit vaccine composed of four known leptospiral FHBPs: LigA domain 7–13 (LigAc), LenA, LcpA, and Lsa23, for its protective efficacy in hamsters. The mono and multisubunit vaccines formulated with LMQ adjuvant, a combination of neutral liposome, monophosphoryl lipid A, and Quillaja saponaria fraction 21, induced high and comparable specific antibody (IgG) production against individual antigens. Hamsters immunized with the multisubunit vaccine showed 60% survival following the challenge by 20× LD50 of Leptospira interrogans serovar Pomona. No significant difference in survival rate and pathological findings of target organs was observed after vaccinations with multisubunit or mono-LigAc vaccines. However, the multisubunit vaccine significantly reduced leptospiral burden in surviving hamsters in comparison with the monosubunit vaccines. Therefore, the multisubunit vaccine conferred partial protection and reduced renal colonization against virulence Leptospira infection in hamsters. Our multisubunit formulation could represent a promising vaccine against leptospirosis. Full article
(This article belongs to the Section Veterinary Vaccines)
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Open AccessArticle
Sea Bass Immunization to Downsize the Betanodavirus Protein Displayed in the Surface of Inactivated Repair-Less Bacteria
Vaccines 2019, 7(3), 94; https://doi.org/10.3390/vaccines7030094 - 20 Aug 2019
Viewed by 403
Abstract
This work describes immunization of European sea bass (Dicentrarchus labrax) juveniles against viral nervous necrosis virus (VNNV), a betanodavirus causing worldwide mortalities in many fish species. Protection was obtained with the so-called spinycterin vehicles consisting of irreversibly DNA-damaged DNA-repair-less Escherichia coli [...] Read more.
This work describes immunization of European sea bass (Dicentrarchus labrax) juveniles against viral nervous necrosis virus (VNNV), a betanodavirus causing worldwide mortalities in many fish species. Protection was obtained with the so-called spinycterin vehicles consisting of irreversibly DNA-damaged DNA-repair-less Escherichia coli displaying at their surface a downsized VNNV coat antigen. In this work we have (i) maximized bacterial expression levels by downsizing the coat protein of VNNV to a fragment (frgC91–220) containing most of its previously determined antigenicity, (ii) developed a scalable autoinduction culture media for E. coli based in soy-bean rather than in casein hydrolysates, (iii) enriched surface expression by screening different anchors from several prokaryotic sources (anchor + frgC91–220 recombinant products), (iv) preserved frgC91–220 antigenicity by inactivating bacteria by irreversible DNA-damage by means of Ciprofloxacin, and (v) increased safety using a repair-less E. coli strain as chassis for the spinycterins. These spinycterins protected fish against VNNV challenge with partial (Nmistic + frgC91–220) or total (YBEL + frgC91–220) levels of protection, in contrast to fish immunized with frgC91–220 spinycterins. The proposed spinycterin platform has high levels of environmental safety and cost effectiveness and required no adjuvants, thus providing potential to further develop VNNV vaccines for sustainable aquaculture. Full article
(This article belongs to the Section Veterinary Vaccines)
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Open AccessArticle
Attenuation of Zika Virus by Passage in Human HeLa Cells
Vaccines 2019, 7(3), 93; https://doi.org/10.3390/vaccines7030093 - 20 Aug 2019
Viewed by 594
Abstract
Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized that wild-type ZIKV would also be [...] Read more.
Zika virus (ZIKV) is a mosquito-borne Flavivirus. Previous studies have shown that mosquito-transmitted flaviviruses, including yellow fever, Japanese encephalitis, and West Nile viruses, could be attenuated by serial passaging in human HeLa cells. Therefore, it was hypothesized that wild-type ZIKV would also be attenuated after HeLa cell passaging. A human isolate from the recent ZIKV epidemic was subjected to serial HeLa cell passaging, resulting in attenuated in vitro replication in both Vero and A549 cells. Additionally, infection of AG129 mice with 10 plaque forming units (pfu) of wild-type ZIKV led to viremia and mortality at 12 days, whereas infection with 103 pfu of HeLa-passage 6 (P6) ZIKV led to lower viremia, significant delay in mortality (median survival: 23 days), and increased cytokine and chemokine responses. Genomic sequencing of HeLa-passaged virus identified two amino acid substitutions as early as HeLa-P3: pre-membrane E87K and nonstructural protein 1 R103K. Furthermore, both substitutions were present in virus harvested from HeLa-P6-infected animal tissue. Together, these data show that, similarly to other mosquito-borne flaviviruses, ZIKV is attenuated following passaging in HeLa cells. This strategy can be used to improve understanding of substitutions that contribute to attenuation of ZIKV and be applied to vaccine development across multiple platforms. Full article
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Open AccessArticle
The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate
Vaccines 2019, 7(3), 92; https://doi.org/10.3390/vaccines7030092 - 20 Aug 2019
Viewed by 622
Abstract
We developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase [...] Read more.
We developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of “DNA-4”. This was a multicenter, double-blind, placebo-controlled clinical trial of safety, and dose selection of “DNA-4” in HIV-1 infected people receiving antiretroviral therapy (ART). Fifty-four patients were randomized into 3 groups (17 patients—group DNA-4 0.25 mg, 17 patients—group DNA-4 0.5 mg, 20 patients—the placebo group). All patients were immunized 4 times on days 0, 7, 11, and 15 followed by a 24-week follow-up period. “DNA-4” was found to be safe and well-tolerated at doses of 0.25 mg and 0.5 mg. We found that the amplitudes of the spontaneous viral load increases in three patients immunized with the candidate DNA vaccine were much higher than that in placebo group—2800, 180,000 and 709 copies/mL, suggesting a possible influence of therapeutic DNA vaccination on viral reservoirs in some patients on ART. We hypothesize that this influence was associated with the reactivation of proviral genomes. Full article
(This article belongs to the Special Issue Advances in DNA Vaccines)
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