Topical Collection "Vaccines against Infectious Diseases"

Editor

Dr. E.Diane Williamson
E-Mail Website1 Website2
Guest Editor
Defence Science & Technology Laboratory, Porton Down, Salisbury, Wilts SP4 0JQ, UK
Interests: vaccines; Burkholderia; anthrax; Yersinia; host responses; biodefence; emerging pathogens;MERS

Topical Collection Information

Dear Colleagues,

We are launching a collection on vaccines against infectious disease, in which we propose to cover aspects of vaccine design, development , formulation, clinical trial and deployment.  Despite advances in global healthcare, there is still a clear need for more vaccines against infectious disease, underlined in the past year or more by the coronavirus pandemic. In this series, we will invite a broad range of papers to cover the following topics:

  • Vaccines to counter anti-microbial resistance
  • Vaccines to eradicate endemic disease-opportunities and challenges
  • Vaccines to prevent zoonotic transmission-targeting the animal reservoir
  • Vaccine platforms-advantages and disadvantages
  • Clinical trial design for reactive and preventive vaccination
  • Vaccine deployment in outbreak settings-lessons learned
  • Advances in vaccine formulation and adjuvantisation
  • WHO pre-qualification of vaccines-creating a Target Product Profile
  • Clinical view on routinisation of vaccines
  • How do we prepare for vaccines against the as yet unknown?

Dr. E.Diane Williamson
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 papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection 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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • clinical trial
  • vaccine
  • formulation
  • platform
  • endemic disease
  • outbreak
  • preventive
  • reactive
  • vaccination

Published Papers (15 papers)

2022

Jump to: 2021

Article
Predictors of Survival after Vaccination in a Pneumonic Plague Model
Vaccines 2022, 10(2), 145; https://doi.org/10.3390/vaccines10020145 - 19 Jan 2022
Viewed by 103
Abstract
Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine [...] Read more.
Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. Results: Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. Conclusions: These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy. Full article
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Article
Age and Primary Vaccination Background Influence the Plasma Cell Response to Pertussis Booster Vaccination
Vaccines 2022, 10(2), 136; https://doi.org/10.3390/vaccines10020136 - 18 Jan 2022
Viewed by 103
Abstract
Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole-cell to acellular pertussis vaccines, although other factors may also contribute. Here, [...] Read more.
Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole-cell to acellular pertussis vaccines, although other factors may also contribute. Here, we applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. Participants were divided over four age cohorts. We compared longitudinal kinetics within each cohort and between the different cohorts. Changes in the B-cell compartment were correlated to numbers of vaccine-specific B- and plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days postvaccination was the most prominent cellular change in all age groups and was most pronounced for more mature IgG1+ plasma cells. Plasma cell responses were stronger in individuals primed with whole-cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ and IgA1+ plasma cell expansion correlated with FHA-, Prn-, or PT- specific serum IgG or IgA levels. Our study indicates plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and primary vaccination backgrounds. Full article
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Article
Antibody Levels at 3-Years Follow-Up of a Third Dose of Measles-Mumps-Rubella Vaccine in Young Adults
Vaccines 2022, 10(1), 132; https://doi.org/10.3390/vaccines10010132 - 17 Jan 2022
Viewed by 120
Abstract
Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing [...] Read more.
Mumps outbreaks and breakthrough infections of measles and rubella have raised concerns about waning of vaccine-induced immunity after two doses of measles-mumps-rubella (MMR) vaccination. In the present follow-up study, serum IgG antibodies against mumps, measles and rubella, as well as the functional neutralizing antibodies against both the mumps vaccine strain and mumps outbreak strains were measured longitudinally in young adults that received a third MMR (MMR3) dose. The mumps-specific IgG and virus neutralizing antibody levels at 3 years after vaccination were still elevated compared to pre-vaccination antibody levels, although the differences were smaller than at earlier timepoints. Interestingly, subjects with low antibody levels to mumps before vaccination benefited the most as they showed the strongest antibody increase after an MMR3 dose. Three years after an MMR3 dose, all subjects had antibody levels to measles and rubella above the internationally agreed antibody cutoff levels for clinical protection. Our data support the recommendation that an MMR3 dose may provide additional protection for those that have become susceptible to mumps virus infection during outbreaks. MMR3 also resulted in an increase in anti-measles and rubella antibody levels that lasted longer than might have been expected. Full article
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Article
Development and Properties of Francisella tularensis Subsp. holarctica 15 NIIEG Vaccine Strain without the recD Gene
Vaccines 2022, 10(1), 108; https://doi.org/10.3390/vaccines10010108 - 11 Jan 2022
Viewed by 94
Abstract
The genomic analysis of all subspecies F. tularensis, as found in Gen Bank NCBI, reveals the presence of genes encoding proteins like to the multifunctional RecBCD enzyme complex in E. coli and other bacteria. To date, the role of the recD gene [...] Read more.
The genomic analysis of all subspecies F. tularensis, as found in Gen Bank NCBI, reveals the presence of genes encoding proteins like to the multifunctional RecBCD enzyme complex in E. coli and other bacteria. To date, the role of the recD gene in F. tularensis, which encodes the alpha chain of exonuclease V, in DNA metabolism processes, has not been studied either in vitro or in vivo. F. tularensis subsp. holarctica 15 NIIEG, a vaccine strain, served as the basis to create the F. tularensis 15D strain with recD deletion. The lack of the recD gene suppresses the integration of suicide plasmids with F. tularensis genome fragments into the chromosome. The modified strain showed reduced growth in vitro and in vivo. This study shows that such deletion significantly reduces the virulence of the strain in BALB/c mice. Full article
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Article
Immunity to Sda1 Protects against Infection by Sda1+ and Sda1 Serotypes of Group A Streptococcus
Vaccines 2022, 10(1), 102; https://doi.org/10.3390/vaccines10010102 - 11 Jan 2022
Viewed by 126
Abstract
Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not [...] Read more.
Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases. Full article
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Article
Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines
Vaccines 2022, 10(1), 75; https://doi.org/10.3390/vaccines10010075 - 04 Jan 2022
Viewed by 290
Abstract
With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated [...] Read more.
With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector–mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure. Full article
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2021

Jump to: 2022

Article
Has Clinical and Epidemiological Varicella Burden Changed over Time in Children? Overview on Hospitalizations, Comorbidities and Costs from 2010 to 2017 in Italy
Vaccines 2021, 9(12), 1485; https://doi.org/10.3390/vaccines9121485 - 15 Dec 2021
Viewed by 430
Abstract
According to WHO estimates, varicella disease is responsible of a worldwide significant burden in terms of hospitalizations, complications, and deaths, with more than 90% of cases under 12 years old. This study aims at evaluating the clinical, epidemiological, and economic burden of varicella [...] Read more.
According to WHO estimates, varicella disease is responsible of a worldwide significant burden in terms of hospitalizations, complications, and deaths, with more than 90% of cases under 12 years old. This study aims at evaluating the clinical, epidemiological, and economic burden of varicella in Ligurian children, about comorbidities, organizational variables, and vaccination coverages from 2010 to 2017, in terms of Emergency Department accesses and hospitalizations. The overall hospitalization rate was 179.76 (per 100,000 inhab.), with a gradual but significant decline since 2015, when universal varicella vaccination was introduced in Liguria (p < 0.0001). The risk of being hospitalized for complicated varicella in subjects with at least one comorbidity was significantly higher than in subjects without comorbidities (p = 0.0016). The economic analysis showed higher costs in subjects with complicated varicella who were 0–3 years old. This age group showed higher costs also considering extra-hospital costs for both outpatient procedures and pharmaceutical costs (p < 0.0001). The results confirm the relevant burden of varicella, especially in the 0–3 age group and in children with comorbidities. Thus, vaccination with the achievement of adequate vaccination coverages is confirmed to be a necessary control strategy to reduce hospitalizations and associated complications with important economic benefits. Full article
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Article
12 Months Persistent Immunogenicity after Hepatitis B Vaccination in Patients with Type 2 Diabetes and Immunogenicity of Revaccination in Non-Responders: An Open-Label Randomized Controlled Trial
Vaccines 2021, 9(12), 1407; https://doi.org/10.3390/vaccines9121407 - 29 Nov 2021
Viewed by 405
Abstract
Background: In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. Methods: In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose [...] Read more.
Background: In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. Methods: In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose hepatitis B vaccines (Group D20SC 0-1-6; Group D20CHO 0-1-6; Group ND20SC 0-1-6). Participants were followed up at 12 months after being fully vaccinated. One dose of the vaccine was randomly administered to non-responders. Chi-square test was used to compare the differences in response rate between two groups. Results: The anti-HBs response rates of three groups decreased from 84.1%, 89.1% and 88.3% at one month to 64.6%, 79.8% and 71.4% at twelve months. There was no statistical difference in the immune response rates between Group D20SC 0-1-6 and Group ND20SC 0-1-6; however, that of Group D20CHO 0-1-6 was higher than that of Group D20SC 0-1-6. After revaccination, the geometric mean concentrations were 491.7 mIU/mL and 29.7 mIU/mL after using vaccines containing 60 μg and 20 μg HBsAg. Conclusions: At 12 months, immune response in diabetic patients were not significantly different from that in healthy people. Revaccination with one dose of hepatitis B vaccine containing 60 μg HBsAg for non-responders was more satisfactory. Full article
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Article
Side Effects of COVID-19 Pfizer-BioNTech mRNA Vaccine in Children Aged 12–18 Years in Saudi Arabia
Vaccines 2021, 9(11), 1297; https://doi.org/10.3390/vaccines9111297 - 09 Nov 2021
Cited by 1 | Viewed by 2039
Abstract
Background: Massive vaccination campaigns have been undertaken globally to combat the spread of the Coronavirus Disease 2019 (COVID-19). While most COVID-19 vaccines have shown excellent efficacy and safety profiles in clinical studies, real-world monitoring of vaccine safety is still important. In this [...] Read more.
Background: Massive vaccination campaigns have been undertaken globally to combat the spread of the Coronavirus Disease 2019 (COVID-19). While most COVID-19 vaccines have shown excellent efficacy and safety profiles in clinical studies, real-world monitoring of vaccine safety is still important. In this study, we aimed to investigate the early side effects of Pfizer-BioNTech (BNT162b2) mRNA vaccine in children between 12–18 years old in Saudi Arabia. Method: To investigate the side effects in children in this age range following the administration of either one or two doses of Pfizer-BioNTech (BNT162b2) mRNA vaccine, we conducted a retrospective, cross-sectional study using a self-administered online survey. General and demographic data were collected, and vaccine-associated side effects following vaccination were evaluated. Results: The study recruited a total of 965 eligible participants. Overall, 571 (60%) of the study participants reported at least one side effect following Pfizer-BioNTech (BNT162b2) mRNA vaccination. The most frequently reported side effects were pain or redness at the site of injection (90%), fatigue (67%), fever (59%), headache (55%), nausea or vomiting (21%), and chest pain and shortness of breath (20%). Joint or bone pain were reported less frequently among our participants (2%). Our data showed that more female participants reported side effects compared to male participants, with 52% and 48%, respectively. Side effects were more common after the second dose compared to the first dose in our study cohort. Conclusions: While 60% of the children (12–18 years old) who received Pfizer-BioNTech (BNT162b2) mRNA vaccine reported side effects, our data showed that these side effects were not different from those that were reported in the clinical trials which lasted only for a few days. Side effects were more common after the second dose. Larger epidemiological and molecular studies are needed to evaluate the safety and the effectiveness of COVID-19 vaccine in protection of children against SARS-CoV-2 reinfections. Full article
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Article
Avian Cell Line DuckCelt®-T17 Is an Efficient Production System for Live-Attenuated Human Metapneumovirus Vaccine Candidate Metavac®
Vaccines 2021, 9(10), 1190; https://doi.org/10.3390/vaccines9101190 - 16 Oct 2021
Viewed by 562
Abstract
The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with [...] Read more.
The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt®-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac®, SH gene-deleted A1/C-85473 HMPV). To that end, we characterized the operational parameters of MOI, cell density, and trypsin addition to achieve the optimal production of Metavac®, and demonstrated that the DuckCelt®-T17 cell line is permissive and well-adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, and its capacity to induce efficient neutralizing antibodies in a BALB/c mouse model. Our results suggest that the DuckCelt®-T17 avian cell line is a very promising platform for the scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac®. Full article
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Review
COVID-19 Vaccinations: A Comprehensive Review of Their Safety and Efficacy in Special Populations
Vaccines 2021, 9(10), 1097; https://doi.org/10.3390/vaccines9101097 - 28 Sep 2021
Cited by 2 | Viewed by 1370
Abstract
COVID-19 has been spreading worldwide since late 2019. There is no definitive cure to date. Global vaccination programs are urgently required to confer herd immunity, reducing the incidence of COVID-19 infections and associated morbidity and mortality. However, a significant proportion of special populations [...] Read more.
COVID-19 has been spreading worldwide since late 2019. There is no definitive cure to date. Global vaccination programs are urgently required to confer herd immunity, reducing the incidence of COVID-19 infections and associated morbidity and mortality. However, a significant proportion of special populations are hesitant to receive vaccination due to their special conditions, namely, age (pediatrics and geriatrics), immunocompromised state, autoimmune diseases, chronic cardiovascular and pulmonary conditions, active or treated cancers, and pregnancy. This review aims to evaluate the existing evidence of COVID-19 vaccinations on these special populations and to provide clues to guide vaccination decision making to balance the benefits and risks of vaccinations. Full article
Article
Hepatitis B Vaccination Coverage Rates and Associated Factors: A Community-Based, Cross-Sectional Study Conducted in Beijing, 2019–2020
Vaccines 2021, 9(10), 1070; https://doi.org/10.3390/vaccines9101070 - 24 Sep 2021
Cited by 1 | Viewed by 576
Abstract
Hepatitis B vaccination coverage rates are low throughout most populations in China. Factors influencing low coverage rates, including population-specific hepatitis B vaccination barriers, may inform policies that promote vaccination. A cross-sectional survey of residents from 43 communities assessed their vaccination status and identified [...] Read more.
Hepatitis B vaccination coverage rates are low throughout most populations in China. Factors influencing low coverage rates, including population-specific hepatitis B vaccination barriers, may inform policies that promote vaccination. A cross-sectional survey of residents from 43 communities assessed their vaccination status and identified associated factors via uni- and multivariable logistic regression and subgroup analyses. In total, 11,280 of 36,007 respondents received a hepatitis B vaccine, indicating a 31.33% coverage rate. Multivariable logistic regression revealed non-Beijing (odds ratio (OR) = 0.81; 95% confidence interval (CI): 0.76–0.85) and residents who self-rated their health as very healthy (OR = 0.82; 95% CI: 0.68–0.99) were unlikely to be vaccinated. Farmers (OR = 1.68; 95% CI: 1.51–1.86), commerce and service workers (OR = 1.82; 95% CI, 1.63–2.04), government employees (OR = 1.56; 95% CI: 1.38–1.77), professionals and technicians (OR = 1.85; 95% CI: 1.63–2.09), and students (OR = 1.69; 95% CI: 1.10–2.59) had increased hepatitis B vaccination rates. The multivariable assessment revealed hepatitis B vaccination coverage rates are associated with confirmed or suspected family cases, vaccination unwillingness or uncertainty, and unawareness of its prevention of the hepatitis B virus. Low hepatitis B vaccination coverage rates among Beijing subpopulations highlight the need for improved strategies, including those that target specific populations. Full article
Review
An Update on mRNA-Based Viral Vaccines
Vaccines 2021, 9(9), 965; https://doi.org/10.3390/vaccines9090965 - 29 Aug 2021
Cited by 1 | Viewed by 1550
Abstract
With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA [...] Read more.
With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was enabled with previous innovations in nucleoside modifications during in vitro transcription and lipid nanoparticle delivery materials of mRNA. Recent updates are briefly described in the status of mRNA vaccines against SARS-CoV-2, influenza virus, and other viral pathogens. Unique features of mRNA vaccine platforms and future perspectives are discussed. Full article
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Article
In Vitro Priming of Human T Cells by Dendritic Cells Provides a Screening Tool for Candidate Vaccines for Burkholderia pseudomallei
Vaccines 2021, 9(8), 929; https://doi.org/10.3390/vaccines9080929 - 22 Aug 2021
Viewed by 786
Abstract
Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei [...] Read more.
Murine dendritic cells, when pulsed with heat-killed Burkholderia pseudomallei and used to immunise naïve mice, have previously been shown to induce protective immunity in vivo. We have now demonstrated the in vitro priming of naïve human T cells against heat-killed B. pseudomallei, by co-culture with syngeneic B. pseudomallei-pulsed dendritic cells. Additionally, we have enriched the DC fraction such that a study of the differential response induced by pulsed DCs of either myeloid or plasmacytoid lineage in syngeneic human T cells was achievable. Whilst both mDCs and pDCs were activated by pulsing, the mDCs contributed the major response to B. pseudomallei with the expression of the migration marker CCR7 and a significantly greater secretion of the proinflammatory TNFα and IL1β. When these DC factions were combined and used to prime syngeneic T cells, a significant proliferation was observed in the CD4+ fraction. Here, we have achieved human T cell priming in vitro with unadjuvanted B. pseudomallei, the causative organism of melioidosis, for which there is currently no approved vaccine. We propose that the approach we have taken could be used to screen for the human cellular response to candidate vaccines and formulations, in order to enhance the cell-mediated immunity required to protect against this intracellular pathogen and potentially more broadly against other, difficult-to-treat intracellular pathogens. To date, the polysaccharide capsule of B. pseudomallei, fused to a standard carrier protein, e.g., Crm, looks a likely vaccine candidate. Dendritic cells (DCs), providing, as they do, the first line of defence to infection, process and present microbial products to the immune system to direct downstream immune responses. Here, we have sought to use DCs ex vivo to identify immunogenic products from heat-killed B. pseudomallei. Using practical volumes of fresh human donor blood, we show that heat-killed B. pseudomallei activated and stimulated the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DCs. Furthermore, B. pseudomallei-pulsed DCs cultured with naïve syngeneic T cells ex vivo, induced the activation and proliferation of the CD4+ T-cell population, which was identified by cell surface marker staining using flow cytometry. Thus, both DC subsets are important for driving primary T helper cell responses to B. pseudomallei in healthy individuals and have the potential to be used to identify immunogenic components of B. pseudomallei for future therapies and vaccines. Full article
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Article
Chlamydia trachomatis Cross-Serovar Protection during Experimental Lung Reinfection in Mice
Vaccines 2021, 9(8), 871; https://doi.org/10.3390/vaccines9080871 - 06 Aug 2021
Viewed by 650
Abstract
Chlamydia trachomatis causes most bacterial sexually transmitted diseases worldwide. Different major outer membrane proteins (MOMPs) define various serovars of this intracellular pathogen: In women, D to L3 can cause urethritis, cervicitis, salpingitis, and oophoritis, and, thus, infertility. Protective immunity might be serovar-specific since [...] Read more.
Chlamydia trachomatis causes most bacterial sexually transmitted diseases worldwide. Different major outer membrane proteins (MOMPs) define various serovars of this intracellular pathogen: In women, D to L3 can cause urethritis, cervicitis, salpingitis, and oophoritis, and, thus, infertility. Protective immunity might be serovar-specific since chlamydial infection does not appear to induce an effective acquired immunity and reinfections occur. A better understanding of induced cross-serovar protection is essential for the selection of suitable antigens in vaccine development. In our mouse lung infection screening model, we evaluated the urogenital serovars D, E, and L2 in this regard. Seven weeks after primary infection or mock-infection, respectively, mice were infected a second time with the identical or one of the other serovars. Body weight and clinical score were monitored for 7 days. Near the peak of the second lung infection, bacterial load, myeloperoxidase, IFN-γ, and TNF-α in lung homogenate, as well as chlamydia-specific IgG levels in blood were determined. Surprisingly, compared with mice that were infected then for the first time, almost independent of the serovar combination used, all acquired parameters of disease were similarly diminished. Our reinfection study suggests that efficient cross-serovar protection could be achieved by a vaccine combining chlamydial antigens that do not include nonconserved MOMP regions. Full article
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