Advances in Vaccine Development and Immunotherapies

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (10 March 2021) | Viewed by 86703

Special Issue Editors

1. Research and Business Development, Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2. Department of Medicine, University of Oklahoma, Oklahoma, OK 73126, USA
Interests: immunotherapy; CAR-T cells; tumor microenvironment; checkpoint protein; hypoxia; tumor survival signaling
Special Issues, Collections and Topics in MDPI journals

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Assistant Guest Editor
Vascular Program, Department of Genetic Medicine, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: gene transcription in oxygen biology; autophagy; ubiquitin-proteosome system; cell signaling; influenza virus; dengue virus; program cell death; epigenetics; drug discovery and development; chemical biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During Covid-19 pandemic, it is very important to submit reports on vaccine development. Vaccine development can include vaccines against viral diseases, dendritic cell vaccines against cancer or other diseases. In addition, this issue can involve recent development of new immunotherapies against cancer such as chimeric antigen receptor (CAR) T cells therapies, checkpoint inhibitors, monoclonal antibodies, bi-specific antibodies, and combination therapies. The reports on pre-clinical vaccine development, clinical trial data and reviews can be submitted to this issue.

Dr. Vita Golubovskaya
Guest Editor
Dr. Emmanuel Datan
Assistant Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • Vaccine
  • immunotherapy
  • CAR-T
  • cancer
  • antibody

Published Papers (25 papers)

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11 pages, 2749 KiB  
Article
Establishment of Recombinant Eimeria acervulina Expressing Multi-Copies M2e Derived from Avian Influenza Virus H9N2
Vaccines 2021, 9(7), 791; https://doi.org/10.3390/vaccines9070791 - 16 Jul 2021
Cited by 9 | Viewed by 2388
Abstract
The potential of Eimeria parasites as live vaccine vectors has been reported with successful genetic manipulation on several species like E. tenella, E. mitis and E. necatrix. Among seven Eimeria species infecting chickens, E. acervulina is a highly prevalent, moderately pathogenic species. [...] Read more.
The potential of Eimeria parasites as live vaccine vectors has been reported with successful genetic manipulation on several species like E. tenella, E. mitis and E. necatrix. Among seven Eimeria species infecting chickens, E. acervulina is a highly prevalent, moderately pathogenic species. Thus, it is valuable for the study of transfection and for use as a potential as vaccine vector. In this study, a plasmid containing expression cassette with enhanced yellow fluorescent protein (EYFP), red fluorescent protein (RFP) and 12 copies of extracellular domain of H9N2 avian influenza virus M2 (M2e) protein was used for the transfection. Nucleofected sporozoites were inoculated into birds through wing vein. Recombinant E. acervulina oocysts with 0.1% EYFP+ and RFP+ populations were collected from the feces of the inoculated birds. The fluorescent rate of transgenic parasites reached over 95% after nine successive propagations with a pyrimethamine selection in vivo and fluorescent-activated cell sorting (FACS) of progeny oocysts. The expression of M2e in the transgenic parasites (EaM2e) was confirmed by Western blot and its cytoplasm localization in sporozoites was displayed by an indirect immunofluorescent assay (IFA). Meanwhile, we found that the fecundity of EaM2e was equivalent to that of wild type E. acervulina (EaWT). Taken together, the stable transfection of E. acervulina was successfully established. Future studies will focus on whether transgenic E. acervulina can serve as a live vaccine vector. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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16 pages, 2195 KiB  
Article
Association between Venom Immunotherapy and Changes in Serum Protein—Peptide Patterns
Vaccines 2021, 9(3), 249; https://doi.org/10.3390/vaccines9030249 - 12 Mar 2021
Cited by 5 | Viewed by 2628
Abstract
Venom immunotherapy (VIT) is administered to allergic patients to reduce the risk of dangerous systemic reactions following an insect sting. To better understand the mechanism of this treatment and its impact on the human organism, we analysed serum proteomic patterns obtained at five [...] Read more.
Venom immunotherapy (VIT) is administered to allergic patients to reduce the risk of dangerous systemic reactions following an insect sting. To better understand the mechanism of this treatment and its impact on the human organism, we analysed serum proteomic patterns obtained at five time-points from Hymenoptera-venom-allergic patients undergoing VIT. For statistical analyses, patients were additionally divided into two groups (high responders and low responders) according to serum sIgG4 levels. VIT was found to be associated with changes in seven proteins: the fibrinogen alpha chain, complement C4-A, complement C3, filamin-B, kininogen-1, myosin-9 and inter-alpha-trypsin inhibitor heavy chain H1. The number of discriminative m/z (mass-to-charge ratio) features increased up to the 90th day of VIT, which may be associated with the development of immunity after the administration of increased venom doses. It may also suggest that during VIT, there may occur processes involved not only in protein synthesis but also in protein degradation (caused by proteolytic venom components). The results are consistent with measured serum sIgG4 levels, which increased from 2.04 mgA/I at baseline to 7.25 mgA/I at 90 days. Moreover, the major proteomic changes were detected separately in the high responder group. This may suggest that changes in protein–peptide profiles reflect the actual response to VIT. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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14 pages, 3468 KiB  
Article
Immunity to TBEV Related Flaviviruses with Reduced Pathogenicity Protects Mice from Disease but Not from TBEV Entry into the CNS
Vaccines 2021, 9(3), 196; https://doi.org/10.3390/vaccines9030196 - 26 Feb 2021
Cited by 7 | Viewed by 3439
Abstract
Tick-borne encephalitis virus (TBEV) is a leading cause of vector-borne viral encephalitis with expanding endemic regions across Europe. In this study we tested in mice the efficacy of preinfection with a closely related low-virulent flavivirus, Langat virus (LGTV strain TP21), or a naturally [...] Read more.
Tick-borne encephalitis virus (TBEV) is a leading cause of vector-borne viral encephalitis with expanding endemic regions across Europe. In this study we tested in mice the efficacy of preinfection with a closely related low-virulent flavivirus, Langat virus (LGTV strain TP21), or a naturally avirulent TBEV strain (TBEV-280) in providing protection against lethal infection with the highly virulent TBEV strain (referred to as TBEV-Hypr). We show that prior infection with TP21 or TBEV-280 is efficient in protecting mice from lethal TBEV-Hypr challenge. Histopathological analysis of brains from nonimmunized mice revealed neuronal TBEV infection and necrosis. Neuroinflammation, gliosis, and neuronal necrosis was however also observed in some of the TP21 and TBEV-280 preinfected mice although at reduced frequency as compared to the nonimmunized TBEV-Hypr infected mice. qPCR detected the presence of viral RNA in the CNS of both TP21 and TBEV-280 immunized mice after TBEV-Hypr challenge, but significantly reduced compared to mock-immunized mice. Our results indicate that although TBEV-Hypr infection is effectively controlled in the periphery upon immunization with low-virulent LGTV or naturally avirulent TBEV 280, it may still enter the CNS of these animals. These findings contribute to our understanding of causes for vaccine failure in individuals vaccinated with TBE vaccines. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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14 pages, 1163 KiB  
Article
A Bacterially-Expressed Recombinant Envelope Protein from Usutu Virus Induces Neutralizing Antibodies in Rabbits
Vaccines 2021, 9(2), 157; https://doi.org/10.3390/vaccines9020157 - 16 Feb 2021
Cited by 4 | Viewed by 2346
Abstract
Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of [...] Read more.
Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of other flaviviruses, like West Nile virus and Zika virus, and will spread via its mosquito vectors and bird hosts to other parts of the world. Several cases of human infections by Usutu virus have already been published. Anticipating this spread, development of an efficacious vaccine would be highly desirable. Method: This study describes the production in E. coli, purification, and refolding of a partial USUV envelope protein. Prior to immunization, the protein was characterized using size exclusion chromatography, transmission electron microscopy and dynamic light scattering, showing the limited presence of virus-like structures, indicating that the protein solution is probably a mixture of mono and multimeric envelope proteins. Results: Immunizations of two rabbits with the refolded E-protein fraction, mixed with a strong adjuvant, resulted in the generation of neutralizing antibodies, as evidenced in an in vitro assay. Discussion: The way forward towards a subunit vaccine against Usutu virus infection is discussed. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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19 pages, 8298 KiB  
Article
Construction and Immunogenicity Comparison of Three Virus-Like Particles Carrying Different Combinations of Structural Proteins of Avian Coronavirus Infectious Bronchitis Virus
Vaccines 2021, 9(2), 146; https://doi.org/10.3390/vaccines9020146 - 11 Feb 2021
Cited by 1 | Viewed by 2235
Abstract
Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs); VLPs carrying the S and M proteins (SM-VLPs); and [...] Read more.
Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs); VLPs carrying the S and M proteins (SM-VLPs); and VLPs carrying the M and E proteins (ME-VLPs) from the dominant serotype representative strain GX-YL5 in China. The neutralizing antibody response induced by the SME-VLPs was similar to that induced by the inactivated oil vaccine (OEV) of GX-YL5, and higher than those induced by the SM-VLPs, ME-VLPs and commercial live vaccine H120. More importantly, the SME-VLPs elicited higher percentages of CD4+ and CD8+ T lymphocytes than the SM-VLPs, ME-VLPs and OEV of GX-YL5. Compared with the OEV of GX-YL5, higher levels of IL-4 and IFN-γ were also induced by the SME-VLPs. Moreover, the mucosal immune response (sIgA) induced by the SME-VLPs in the tear and oral swabs was comparable to that induced by the H120 vaccine and higher than that induced by the OEV of GX-YL5. In the challenge experiment, the SME-VLPs resulted in significantly lower viral RNA levels in the trachea and higher protection scores than the OEV of GX-YL5 and H120 vaccines, and induced comparable viral RNA levels in the kidneys, and tear and oral swabs to the OEV of GX-YL5. In summary, among the three VLPs, the SME-VLPs carrying the S, M and E proteins of IBV could stimulate the strongest humoral, cellular and mucosal immune responses and provide effective protection, indicating that it would be an attractive vaccine candidate for IB. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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15 pages, 674 KiB  
Article
Peptide Vaccination against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
Vaccines 2021, 9(2), 133; https://doi.org/10.3390/vaccines9020133 - 06 Feb 2021
Cited by 7 | Viewed by 2274
Abstract
Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for [...] Read more.
Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for seronegative end-stage renal disease patients waiting for kidney transplantation. Methods: The highly immunogenic nonamer peptide NLVPMVATV derived from CMV phosphoprotein 65(CMVpp65) in a water-in-oil emulsion (Montanide™) plus imiquimod (Aldara™) as an adjuvant was administered subcutaneously four times biweekly. Clinical course as well as immunological responses were monitored using IFN-γ ELISpot assays and flow cytometry for CMV-specific CD8+ T cells. Results: Peptide vaccination was well tolerated, and no drug-related serious adverse events were detected except for Grade I–II local skin reactions. Five of the 10 patients (50%) mounted any immune response (responders) and 40% of the patients presented CMV-specific CD8+ T cell responses elicited by these prophylactic vaccinations. No responders experienced CMV reactivation in the 18 months post-transplantation, while all non-responders reactivated. Conclusion: CMVpp65 peptide vaccination was safe, well tolerated, and clinically encouraging in seronegative end-stage renal disease patients waiting for kidney transplantation. Further studies with larger patient cohorts are planned. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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6 pages, 217 KiB  
Communication
Molecular Epidemiology of Group A Streptococcus Infections in The Gambia
Vaccines 2021, 9(2), 124; https://doi.org/10.3390/vaccines9020124 - 04 Feb 2021
Cited by 6 | Viewed by 2454
Abstract
Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we [...] Read more.
Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
14 pages, 2783 KiB  
Article
Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine
Vaccines 2021, 9(2), 118; https://doi.org/10.3390/vaccines9020118 - 03 Feb 2021
Cited by 3 | Viewed by 2236
Abstract
Tobacco smoking continues to be a global epidemic and the leading preventable cause of cancer and cardiovascular disease. Nicotine vaccines have been investigated as an alternative to currently available smoking cessation strategies as a means to increase rates of success and long-term abstinence. [...] Read more.
Tobacco smoking continues to be a global epidemic and the leading preventable cause of cancer and cardiovascular disease. Nicotine vaccines have been investigated as an alternative to currently available smoking cessation strategies as a means to increase rates of success and long-term abstinence. Recently, we demonstrated that a mucosal nicotine vaccine was able to induce robust mucosal and systemic antibodies when delivered heterologously using intranasal and intramuscular routes. Herein, we investigated the neutralization ability of the anti-nicotine antibodies using both intranasal and intracardiac nicotine challenges. Combining the extraction of lyophilized organ samples with RP-HPLC methods, we were able to recover between 47% and 56% of the nicotine administered from the blood, brain, heart, and lungs up to 10 min after challenge, suggesting that the interaction of the antibodies with nicotine forms a stable complex independently of the route of vaccination or challenge. Although both challenge routes can be used for assessing systemic antibodies, only the intranasal administration of nicotine, which is more physiologically similar to the inhalation of nicotine, permitted the crucial interaction of nicotine with the mucosal antibodies generated using the heterologous vaccination route. Notably, these results were obtained 6 months after the final vaccination, demonstrating stable mucosal and systemic antibody responses. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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15 pages, 1886 KiB  
Article
OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model
Vaccines 2021, 9(2), 90; https://doi.org/10.3390/vaccines9020090 - 26 Jan 2021
Cited by 6 | Viewed by 2275
Abstract
An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally [...] Read more.
An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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17 pages, 2678 KiB  
Article
Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses
Vaccines 2021, 9(2), 73; https://doi.org/10.3390/vaccines9020073 - 21 Jan 2021
Cited by 24 | Viewed by 3817
Abstract
The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to an effective COVID-19 vaccine may be through the display of SARS-CoV-2 spikes on the surface of virus-like particles, in a manner structurally mimicking spikes on [...] Read more.
The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to an effective COVID-19 vaccine may be through the display of SARS-CoV-2 spikes on the surface of virus-like particles, in a manner structurally mimicking spikes on a native virus. Here we report the development of Newcastle disease virus-like particles (NDVLPs) displaying the prefusion-stabilized SARS-CoV-2 spike ectodomain (S2P). Immunoassays with SARS-CoV-2-neutralizing antibodies revealed the antigenicity of S2P-NDVLP to be generally similar to that of soluble S2P, and negative-stain electron microscopy showed S2P on the NDVLP surface to be displayed with a morphology corresponding to its prefusion conformation. Mice immunized with S2P-NDVLP showed substantial neutralization titers (geometric mean ID50 = 386) two weeks after prime immunization, significantly higher than those elicited by a molar equivalent amount of soluble S2P (geometric mean ID50 = 17). Neutralizing titers at Week 5, two weeks after a boost immunization with S2P-NDVLP doses ranging from 2.0 to 250 μg, extended from 2125 to 4552, and these generally showed a higher ratio of neutralization versus ELISA than observed with soluble S2P. Overall, S2P-NDVLP appears to be a promising COVID-19 vaccine candidate capable of eliciting substantial neutralizing activity. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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9 pages, 2097 KiB  
Communication
Month of Influenza Virus Vaccination Influences Antibody Responses in Children and Adults
Vaccines 2021, 9(2), 68; https://doi.org/10.3390/vaccines9020068 - 20 Jan 2021
Cited by 3 | Viewed by 1448
Abstract
The improvement of influenza virus vaccines and the development of a universal product have been long-standing goals in pre-clinical and clinical research. To meet these goals and to understand the strengths and weaknesses of current vaccine strategies, scientists routinely study human responses toward [...] Read more.
The improvement of influenza virus vaccines and the development of a universal product have been long-standing goals in pre-clinical and clinical research. To meet these goals and to understand the strengths and weaknesses of current vaccine strategies, scientists routinely study human responses toward seasonal influenza vaccines. This research is frequently performed with clinical samples taken throughout an influenza season, often without strict attention to the month of inoculation for each study participant. Here, we ask how the timing of vaccination affects outcomes. Results demonstrate significant influences of inoculation month on the immune response. During the progression from fall to winter months, there are changes in host lifestyles and in the frequencies of clinical/sub-clinical viral infections that can significantly alter vaccine immunogenicity. We now recommend routine assessment of inoculation month during clinical studies to inform data interpretation and expedite the development of successful vaccines. This recommendation is pertinent to numerous vaccine development efforts within and outside the influenza virus field. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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11 pages, 1132 KiB  
Article
Passive Immunization with Recombinant Antibody VLRB-PirAvp/PirBvp—Enriched Feeds against Vibrio parahaemolyticus Infection in Litopenaeus vannamei Shrimp
Vaccines 2021, 9(1), 55; https://doi.org/10.3390/vaccines9010055 - 16 Jan 2021
Cited by 6 | Viewed by 3343
Abstract
The causative agent of acute hepatopancreatic necrosis disease (AHPND) is the bacterium, Vibrio parahaemolyticus, which secretes toxins into the gastrointestinal tract of its host. Vibrio parahaemolyticus toxins A and B (PirAvp/PirBvp) have been implicated in the pathogenesis of [...] Read more.
The causative agent of acute hepatopancreatic necrosis disease (AHPND) is the bacterium, Vibrio parahaemolyticus, which secretes toxins into the gastrointestinal tract of its host. Vibrio parahaemolyticus toxins A and B (PirAvp/PirBvp) have been implicated in the pathogenesis of this disease, and are, therefore, the focus of studies developing treatments for AHPND. We previously produced recombinant antibodies based on the hagfish variable lymphocyte receptor B (VLRB) capable of neutralizing some viruses, suggesting that this type of antibody may have a potential application for treatment of AHPND. Here, recombinant PirAvp/PirBvp, produced using a bacterial expression system, were used as antigens to screen a hagfish VLRB cDNA library to obtain PirAvp/PirBvp-specific antibodies. A cell line secreting these antibodies was established by screening and cloning the DNA extracted from hagfish B cells. Supernatants collected from cells secreting the PirAvp/PirBvp antibodies were collected and concentrated, and used to passively immunize shrimp to neutralize the toxins PirAvp or PirBvp associated with AHPND. Briefly, 10 μg of PirAvp and PirBvp antibodies, 7C12 and 9G10, respectively, were mixed with the shrimp feed, and fed to shrimp for three days consecutive days prior to experimentally infecting the shrimp with V. parahaemolyticus (containing toxins A and B), and resulting mortalities recorded for six days. Results showed significantly higher level of survival in shrimp fed with the PirBvp-9G10 antibody (60%) compared to the group fed the PirAvp-7C12 antibody (3%) and the control group (0%). This suggests that VLRB antibodies may be a suitable alternative to immunoglobulin-based antibodies, as passive immunization treatments for effective management of AHPND outbreaks within shrimp farms. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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12 pages, 1537 KiB  
Article
Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults
Vaccines 2021, 9(1), 25; https://doi.org/10.3390/vaccines9010025 - 07 Jan 2021
Cited by 7 | Viewed by 2054
Abstract
Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought [...] Read more.
Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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16 pages, 1295 KiB  
Article
Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin
Vaccines 2020, 8(4), 781; https://doi.org/10.3390/vaccines8040781 - 20 Dec 2020
Cited by 3 | Viewed by 2647
Abstract
Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in [...] Read more.
Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in embryonated chicken eggs-based vaccine production system, they need to be improved in terms of immunogenicity and potential mammalian pathogenicity. We replaced the PB2 gene alone or the PB2 (polymerase basic protein 2), NP (nucleoprotein), M (matrix protein) and NS (non-structural protein) genes together in the PR8 strain with corresponding genes from AIVs with low pathogenicity to remove mammalian pathogenicity and to match CD8+ T cell epitopes with contemporary HPAI viruses, respectively, without loss of viral fitness. Additionally, we tested the effect of the H103Y mutation of hemagglutinin (HA) on antigen productivity, mammalian pathogenicity and heat/acid stability. The replacement of PB2 genes and the H103Y mutation reduced the mammalian pathogenicity but increased the antigen productivity of the recombinant vaccine strains. The H103Y mutation increased heat stability but unexpectedly decreased acid stability, probably resulting in increased activation pH for HA. Interestingly, vaccination with inactivated recombinant virus with replaced NP, M and NS genes halted challenge virus shedding earlier than the recombinant vaccine without internal genes replacement. In conclusion, we successfully generated recombinant clade 2.3.4.4c H5N6 vaccine strains that were less pathogenic to mammals and more productive and heat stable than conventional PR8-derived recombinant strains by optimization of internal genes and the H103Y mutation of HA. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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19 pages, 4264 KiB  
Article
Recombinant Enterovirus 71 Viral Protein 1 Fused to a Truncated Newcastle Disease Virus NP (NPt) Carrier Protein
Vaccines 2020, 8(4), 742; https://doi.org/10.3390/vaccines8040742 - 07 Dec 2020
Cited by 4 | Viewed by 2445
Abstract
Enterovirus 71 (EV71) is the major causative agent in hand, foot, and mouth disease (HFMD), and it mainly infects children worldwide. Despite the risk, there is no effective vaccine available for this disease. Hence, a recombinant protein construct of truncated nucleocapsid protein viral [...] Read more.
Enterovirus 71 (EV71) is the major causative agent in hand, foot, and mouth disease (HFMD), and it mainly infects children worldwide. Despite the risk, there is no effective vaccine available for this disease. Hence, a recombinant protein construct of truncated nucleocapsid protein viral protein 1 (NPt-VP1198–297), which is capable of inducing neutralizing antibody against EV71, was evaluated in a mouse model. Truncated nucleocapsid protein Newcastle disease virus that was used as immunological carrier fused to VP1 of EV71 as antigen. The recombinant plasmid carrying corresponding genes was constructed by recombinant DNA technology and the corresponding protein was produced in Escherichia coli expression system. The recombinant NPt-VP1198–297 protein had elicited neutralizing antibodies against EV71 with the titer of 1:16, and this result is higher than the titer that is elicited by VP1 protein alone (1:8). It was shown that NPt containing immunogenic epitope(s) of VP1 was capable of inducing a greater functional immune response when compared to full-length VP1 protein alone. It was capable to carry larger polypeptide compared to full-length NP protein. The current study also proved that NPt-VP1198–297 protein can be abundantly produced in recombinant protein form by E. coli expression system. The findings from this study support the importance of neutralizing antibodies in EV71 infection and highlight the potential of the recombinant NPt-VP1198–297 protein as EV71 vaccine. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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16 pages, 2416 KiB  
Article
Cross-Reactive Effects of Vaccines: Heterologous Immunity between Tetanus and Chlamydia
Vaccines 2020, 8(4), 719; https://doi.org/10.3390/vaccines8040719 - 01 Dec 2020
Cited by 4 | Viewed by 2707
Abstract
Vaccines can have heterologous effects on the immune system, i.e., effects other than triggering an immune response against the disease targeted by the vaccine. We investigated whether monoclonal antibodies (mAbs) specific for tetanus could cross-react with Chlamydia and confer heterologous protection against chlamydial [...] Read more.
Vaccines can have heterologous effects on the immune system, i.e., effects other than triggering an immune response against the disease targeted by the vaccine. We investigated whether monoclonal antibodies (mAbs) specific for tetanus could cross-react with Chlamydia and confer heterologous protection against chlamydial infection. The capability of two tetanus-specific mAbs, namely mAb26 and mAb51, to prevent chlamydial infection has been assessed: (i) in vitro, by performing a neutralization assay using human conjunctival epithelial (HCjE) cells infected with Chlamydia trachomatis serovar B, and (ii) in vivo, by using a guinea pig model of Chlamydiacaviae-induced inclusion conjunctivitis. The mAb26 has been superior in comparison with mAb51 in the prevention of chlamydial infection in HCjE cells. The mAb26 has conferred ≈40% inhibition of the infection, compared to less than 5% inhibition in the presence of the mAb51. In vivo, mAb26 significantly diminished ocular pathology intensity in guinea pigs infected with C. caviae compared to either the mAb51-treated or sham-treated guinea pigs. Our data provide insights that tetanus immunization generates antibodies which induce heterologous chlamydial immunity and promote protection beyond the intended target pathogen. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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19 pages, 4284 KiB  
Article
Generation and Characterization of Universal Live-Attenuated Influenza Vaccine Candidates Containing Multiple M2e Epitopes
Vaccines 2020, 8(4), 648; https://doi.org/10.3390/vaccines8040648 - 03 Nov 2020
Cited by 11 | Viewed by 2985
Abstract
Influenza viruses constantly evolve, reducing the overall protective effect of routine vaccination campaigns. Many different strategies are being explored to design universal influenza vaccines capable of protecting against evolutionary diverged viruses. The ectodomain of influenza A M2e protein (M2e) is among the most [...] Read more.
Influenza viruses constantly evolve, reducing the overall protective effect of routine vaccination campaigns. Many different strategies are being explored to design universal influenza vaccines capable of protecting against evolutionary diverged viruses. The ectodomain of influenza A M2e protein (M2e) is among the most promising targets for universal vaccine design. Here, we generated two recombinant live attenuated influenza vaccines (LAIVs) expressing additional four M2e tandem repeats (4M2e) from the N-terminus of the viral hemagglutinin (HA) protein, in an attempt to enhance the M2e-mediated cross-protection. The recombinant H1N1+4M2e and H3N2+4M2e viruses retained growth characteristics attributable to traditional LAIV viruses and induced robust influenza-specific antibody responses in BALB/c mice, although M2e-specific antibodies were raised only after two-dose vaccination with LAIV+4M2e viruses. Mice immunized with either LAIV or LAIV+4M2e viruses were fully protected against a panel of heterologous influenza challenge viruses suggesting that antibody and cell-mediated immunity contributed to the protection. The protective role of the M2e-specific antibody was seen in passive serum transfer experiments, where enhancement in the survival rates between classical LAIV and chimeric H3N2+4M2e LAIV was demonstrated for H3N2 and H5N1 heterologous challenge viruses. Overall, the results of our study suggest that M2e-specific antibodies induced by recombinant LAIV+4M2e in addition to cellular immunity by LAIV play an important role in conferring protection against heterologous viruses. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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18 pages, 3034 KiB  
Article
Anti-S1 MERS-COV IgY Specific Antibodies Decreases Lung Inflammation and Viral Antigen Positive Cells in the Human Transgenic Mouse Model
Vaccines 2020, 8(4), 634; https://doi.org/10.3390/vaccines8040634 - 01 Nov 2020
Cited by 12 | Viewed by 3248
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. No approved prophylactic and therapeutic interventions are currently available. In this study, we have developed egg yolk antibodies (immunoglobulin Y (IgY)) [...] Read more.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. No approved prophylactic and therapeutic interventions are currently available. In this study, we have developed egg yolk antibodies (immunoglobulin Y (IgY)) specific for MERS-CoV spike protein (S1) in order to evaluate their neutralizing efficiency against MERS-CoV infection. S1-specific immunoglobulins were produced by injecting chickens with purified recombinant S1 protein of MERS-CoV at a high titer (5.7 mg/mL egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated that the IgY antibody specifically bound to the MERS-CoV S1 protein. Anti-S1 antibodies were also able to recognize MERS-COV inside cells, as demonstrated by an immunofluorescence assay. Plaque reduction and microneutralization assays showed the neutralization of MERS-COV in Vero cells by anti-S1 IgY antibodies and non-significantly reduced virus titers in the lungs of MERS-CoV-infected mice during early infection, with a nonsignificant decrease in weight loss. However, a statistically significant (p = 0.0196) quantitative reduction in viral antigen expression and marked reduction in inflammation were observed in lung tissue. Collectively, our data suggest that the anti-MERS-CoV S1 IgY could serve as a potential candidate for the passive treatment of MERS-CoV infection. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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17 pages, 1879 KiB  
Article
Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection
Vaccines 2020, 8(4), 584; https://doi.org/10.3390/vaccines8040584 - 03 Oct 2020
Cited by 38 | Viewed by 7964
Abstract
A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and [...] Read more.
A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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23 pages, 2390 KiB  
Article
A Synthetic Modified Live Chimeric Marker Vaccine against BVDV-1 and BVDV-2
Vaccines 2020, 8(4), 577; https://doi.org/10.3390/vaccines8040577 - 02 Oct 2020
Cited by 7 | Viewed by 3516
Abstract
Bovine viral diarrhea virus (BVDV), a pestivirus which exists in the two distinct species BVDV-1 (syn. Pestivirus A) and BVDV-2 (syn. Pestivirus B), is the causative agent of one of the most widespread and economically important virus infections in cattle. For [...] Read more.
Bovine viral diarrhea virus (BVDV), a pestivirus which exists in the two distinct species BVDV-1 (syn. Pestivirus A) and BVDV-2 (syn. Pestivirus B), is the causative agent of one of the most widespread and economically important virus infections in cattle. For economic as well as for animal health reasons, an increasing number of national BVDV control programs were recently implemented. The main focus lies on the detection and removal of persistently infected cattle. The application of efficient marker or DIVA (differentiation of infected from vaccinated animals) vaccines would be beneficial for the eradication success in regions with a high BVDV prevalence to prevent fetal infection and it would allow serological monitoring of the BVDV status also in vaccinated farms. Therefore, a marker vaccine based on the cytopathic (cp) BVDV-1b strain CP7 was constructed as a synthetic backbone (BVDV-1b_synCP7). For serological discrimination of vaccinated from infected animals, the viral protein Erns was substituted by the heterologous Erns of Bungowannah virus (BuPV, species Pestivirus F). In addition, the vaccines were attenuated by a deletion within the type I interferon inhibitor Npro protein encoding sequence. The BVDV-2 vaccine candidate is based on the genetic sequence of the glycoproteins E1 and E2 of BVDV-2 strain CS8644 (CS), which were introduced into the backbone of BVDV-1b_synCP7_ΔNpro_Erns Bungo in substitution of the homologous glycoproteins. Vaccine virus recovery resulted in infectious cytopathic virus chimera that grew to titers of up to 106 TCID50/mL. Both synthetic chimera BVDV-1b_synCP7_ΔNpro_Erns Bungo and BVDV-1b_synCP7_ΔNpro_Erns Bungo_E1E2 BVDV-2 CS were avirulent in cattle, provided a high level of protection in immunization and challenge experiments against both BVDV species and allowed differentiation of infected from vaccinated cattle. Our study presents the first report on an efficient BVDV-1 and -2 modified live marker vaccine candidate and the accompanying commercially available serological marker ELISA system. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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Review

Jump to: Research, Other

14 pages, 263 KiB  
Review
Recent Developments in Vaccines for Bovine Mycoplasmoses Caused by Mycoplasma bovis and Mycoplasma mycoides subsp. mycoides
Vaccines 2021, 9(6), 549; https://doi.org/10.3390/vaccines9060549 - 24 May 2021
Cited by 9 | Viewed by 3862
Abstract
Two of the most important diseases of cattle are caused by mycoplasmas. Mycoplasma bovis is a world-wide bovine pathogen that can cause pneumonia, mastitis and arthritis. It has now spread to most, if not all, cattle-rearing countries. Due to its increasing resistance to [...] Read more.
Two of the most important diseases of cattle are caused by mycoplasmas. Mycoplasma bovis is a world-wide bovine pathogen that can cause pneumonia, mastitis and arthritis. It has now spread to most, if not all, cattle-rearing countries. Due to its increasing resistance to antimicrobial therapy, vaccination is the principal focus of the control of infection, but effective vaccines are currently lacking. Despite being eradicated from most parts of the world, Mycoplasma mycoides subsp. mycoides, the cause of contagious bovine pleuropneumonia (CBPP), continues to plague sub-Saharan Africa, affecting at least 25 countries. Numerous new experimental vaccines have been developed over the last 20 years to improve on protection afforded by the T1/44, a live vaccine in continuous use in Africa for over 60 years, but none so far have succeeded; indeed, many have exacerbated the disease. Tools for diagnosis and control are adequate for eradication but what is necessary are resources to improve vaccine coverage to levels last seen in the 1970s, when CBPP was restricted to a few countries in Africa. This paper summarizes the results of the main studies in the field of experimental mycoplasma vaccines, reviews data on commercially available bacterin vaccines and addresses issues relating to the search for new candidates for effective vaccines to reduce economic losses in the cattle industry caused by these two mycoplasmas. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
22 pages, 646 KiB  
Review
Immune Responses Elicited by Live Attenuated Influenza Vaccines as Correlates of Universal Protection against Influenza Viruses
Vaccines 2021, 9(4), 353; https://doi.org/10.3390/vaccines9040353 - 07 Apr 2021
Cited by 10 | Viewed by 3853
Abstract
Influenza virus infection remains a major public health challenge, causing significant morbidity and mortality by annual epidemics and intermittent pandemics. Although current seasonal influenza vaccines provide efficient protection, antigenic changes of the viruses often significantly compromise the protection efficacy of vaccines, rendering most [...] Read more.
Influenza virus infection remains a major public health challenge, causing significant morbidity and mortality by annual epidemics and intermittent pandemics. Although current seasonal influenza vaccines provide efficient protection, antigenic changes of the viruses often significantly compromise the protection efficacy of vaccines, rendering most populations vulnerable to the viral infection. Considerable efforts have been made to develop a universal influenza vaccine (UIV) able to confer long-lasting and broad protection. Recent studies have characterized multiple immune correlates required for providing broad protection against influenza viruses, including neutralizing antibodies, non-neutralizing antibodies, antibody effector functions, T cell responses, and mucosal immunity. To induce broadly protective immune responses by vaccination, various strategies using live attenuated influenza vaccines (LAIVs) and novel vaccine platforms are under investigation. Despite superior cross-protection ability, very little attention has been paid to LAIVs for the development of UIV. This review focuses on immune responses induced by LAIVs, with special emphasis placed on the breadth and the potency of individual immune correlates. The promising prospect of LAIVs to serve as an attractive and reliable vaccine platforms for a UIV is also discussed. Several important issues that should be addressed with respect to the use of LAIVs as UIV are also reviewed. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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25 pages, 1353 KiB  
Review
Development of Pandemic Vaccines: ERVEBO Case Study
Vaccines 2021, 9(3), 190; https://doi.org/10.3390/vaccines9030190 - 25 Feb 2021
Cited by 33 | Viewed by 4899
Abstract
Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013–2016 Ebola virus disease (EVD) outbreak [...] Read more.
Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013–2016 Ebola virus disease (EVD) outbreak was the largest EVD outbreak to date and the third Public Health Emergency of International Concern in history, so to prevent a pandemic, numerous partners from the public and private sectors combined efforts and resources to develop an investigational Zaire ebolavirus (EBOV) vaccine candidate (rVSVΔG-ZEBOV-GP) as quickly as possible. The rVSVΔG-ZEBOV-GP vaccine was approved as ERVEBOTM by the European Medicines Authority (EMA) and the United States Food and Drug Administration (FDA) in December 2019 after five years of development. This review describes the development program of this EBOV vaccine, summarizes what is known about safety, immunogenicity, and efficacy, describes ongoing work in the program, and highlights learnings applicable to the development of pandemic vaccines. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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19 pages, 858 KiB  
Review
Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections
Vaccines 2020, 8(3), 517; https://doi.org/10.3390/vaccines8030517 - 10 Sep 2020
Cited by 65 | Viewed by 7083
Abstract
Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing [...] Read more.
Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state. In these disorders, epidermal keratinocytes express high amounts of AMPs, which can lead to uncontrolled inflammation. Similarly, LL-37 had several favorable and unfavorable roles in virus replication and disease pathogenesis. Targeting the antiviral and immunomodulatory functions of LL-37 opens a new approach to limit virus dissemination and the progression of disease. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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Other

Jump to: Research, Review

9 pages, 631 KiB  
Perspective
Dissolvable Microneedle Patches to Enable Increased Access to Vaccines against SARS-CoV-2 and Future Pandemic Outbreaks
Vaccines 2021, 9(4), 320; https://doi.org/10.3390/vaccines9040320 - 01 Apr 2021
Cited by 35 | Viewed by 6942
Abstract
Vaccines are an essential component of pandemic preparedness but can be limited due to challenges in production and logistical implementation. While vaccine candidates were rapidly developed against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), immunization campaigns remain an obstacle to achieving herd immunity. [...] Read more.
Vaccines are an essential component of pandemic preparedness but can be limited due to challenges in production and logistical implementation. While vaccine candidates were rapidly developed against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), immunization campaigns remain an obstacle to achieving herd immunity. Dissolvable microneedle patches are advantageous for many possible reasons: improved immunogenicity; dose-sparing effects; expected low manufacturing cost; elimination of sharps; reduction of vaccine wastage; no need for reconstitution; simplified supply chain, with reduction of cold chain supply through increased thermostability; ease of use, reducing the need for healthcare providers; and greater acceptability compared to traditional hypodermic injections. When applied to coronavirus disease 2019 (COVID-19) and future pandemic outbreaks, microneedle patches have great potential to improve vaccination globally and save many lives. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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