Special Issue "Infectious Diseases Immunology"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Infectious Diseases".

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editor

Prof. Dr. Maria Antonia De Francesco
E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, Institute of Microbiology, University of Brescia, P.le Spedali Civili, 1, I-25123 Brescia, Italy
Interests: virus; bacteria; antibacterial resistance; antiviral resistance; molecular epidemiology
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The development of an infectious disease is the result of complex interactions between pathogens and host immune system. It exists a dynamic equilibrium between immune system which elaborates mechanisms to eradicate infections and the evolution of different microbial strategies to overcome immune defences such as antigenic variation, resistance to phagocytic or complement killing and the production of enzymes inactivating some host cellular proteins.

Our immune system is able to enhance protective immunity against an almost unlimited number of pathogens comprising bacteria, viruses, fungi and parasites. Immunity enhancing is traditionally obtained by using vaccines, even if other modalities of immune modulation are currently under investigation. Likewise, besides this friendly aspect (Mr. Hyde) of host immune system, there is a contradictory aspect (Mr. Jeckyll) where the immune system itself is responsible of disease and tissue damage because some microorganisms have evolved ingenious tools to subvert host’s immune responses for their own survival.

In this special issues, all papers, reviews, diagnostic methodologies able to shed new light both on the mechanisms able to enhance immunity or to elucidate the strategies adopted by pathogens to establish immune interference and induce persistent infections are welcome. Also all studies able to clarify the interrelationship between microorganisms and host immune responses are included.

Prof. Maria Antonia De Francesco
Guest Editor

Manuscript Submission Information

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Keywords

  • Infections
  • Vaccine
  • Immunomodulation
  • Immunopathogenesis
  • Immune evasion
  • Humoral immune response
  • Adaptive Immune response

Published Papers (19 papers)

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Research

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Article
Antibody Response to Canine Parvovirus Vaccination in Dogs with Hypothyroidism Treated with Levothyroxine
Vaccines 2021, 9(2), 180; https://doi.org/10.3390/vaccines9020180 - 20 Feb 2021
Cited by 1 | Viewed by 881
Abstract
(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: [...] Read more.
(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: Six dogs with HypoT and healthy age-matched control dogs (n = 23) were vaccinated against CPV with a modified-live vaccine. Hemagglutination inhibition was used to measure antibodies on days 0, 7, and 28. The comparison of the vaccination response of dogs with HypoT and healthy dogs were performed with univariate analysis. (3) Results: Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HypoT (6/6; 95% CI: 55.7–100) and in 100% of healthy dogs (23/23; 95% CI: 83.1–100.0). A ≥4-fold titer increase was observed in none of the dogs with HypoT and in 4.3% of the healthy dogs (1/23; CI95%: <0.01–22.7). Mild vaccine-associated adverse events (VAAEs) were detected in 33.3% of the dogs with HypoT (2/6; 95% CI: 9.3–70.4) and in 43.5% (10/23; 95% CI: 25.6–63.2) of the healthy dogs. (4) Conclusions: There was neither a significant difference in the dogs’ pre-vaccination antibodies (p = 1.000), or vaccination response (p = 0.735), nor in the occurrence of post-vaccination VAAEs (p = 0.798). The vaccination response in dogs with levothyroxine-treated HypoT seems to be similar to that of healthy dogs. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
Article
Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children
Vaccines 2021, 9(2), 101; https://doi.org/10.3390/vaccines9020101 - 28 Jan 2021
Viewed by 528
Abstract
Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of [...] Read more.
Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Comparison of Four SARS-CoV-2 Neutralization Assays
Vaccines 2021, 9(1), 13; https://doi.org/10.3390/vaccines9010013 - 28 Dec 2020
Cited by 13 | Viewed by 1868
Abstract
Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies [...] Read more.
Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Communication
Elucidating the Efficacy of Vaccination against Vibriosis in Lates calcarifer Using Two Recombinant Protein Vaccines Containing the Outer Membrane Protein K (r-OmpK) of Vibrio alginolyticus and the DNA Chaperone J (r-DnaJ) of Vibrio harveyi
Vaccines 2020, 8(4), 660; https://doi.org/10.3390/vaccines8040660 - 06 Nov 2020
Cited by 3 | Viewed by 873
Abstract
Recombinant cell vaccines expressing the OmpK and DnaJ of Vibrio were developed and subsequently, a vaccination efficacy trial was carried out on juvenile seabass (~5 cm; ~20 g). The fish were divided into 5 groups of 50 fish per group, kept in triplicate. [...] Read more.
Recombinant cell vaccines expressing the OmpK and DnaJ of Vibrio were developed and subsequently, a vaccination efficacy trial was carried out on juvenile seabass (~5 cm; ~20 g). The fish were divided into 5 groups of 50 fish per group, kept in triplicate. Groups 1 and 2 were injected with 107 CFU/mL of the inactivated recombinant cells vaccines, the pET-32/LIC-OmpK and pET-32/LIC-DnaJ, respectively. Group 3 was similarly injected with 107 CFU/mL of inactivated E. coli BL21 (DE3), Group 4 with 107 CFU/mL of formalin killed whole cells V. harveyi, and Group 5 with PBS solution. Serum, mucus, and gut lavage were used to determine the antibody levels before all fish were challenged with V. harveyi, V. alginolyticus, and V. parahemolyticus, respectively on day 15 post-vaccination. There was significant increase in the serum and gut lavage antibody titers in the juvenile seabass vaccinated with r-OmpK vaccine. In addition, there was an up-regulation for TLR2, MyD88, and MHCI genes in the kidney and intestinal tissues of r-OmpK vaccinated fish. At the same time, r-OmpK triggered higher expression level of interleukin IL-10, IL-8, IL-1ß in the spleen, intestine, and kidney compared to r-DnaJ. Overall, r-OmpK and r-DnaJ triggered protection by curbing inflammation and strengthening the adaptive immune response. Vaccinated fish also demonstrated strong cross protection against heterologous of Vibrio isolates, the V. harveyi, V. alginolyticus, and V. parahaemolyticus. The fish vaccinated with r-OmpK protein were completely protected with a relative per cent of survival (RPS) of 90 percent against V. harveyi and 100 percent against V. alginolyticus and V. parahaemolyticus. A semi-quantitative PCR detection of Vibrio spp. from the seawater containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. In conclusion, our results suggest r-OmpK as a candidate vaccine molecule against multiple Vibrio strain to prevent vibriosis in marine fish. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Different Long-Term Duration of Seroprotection against Neisseria meningitidis in Adolescents and Middle-Aged Adults after a Single Meningococcal ACWY Conjugate Vaccination in The Netherlands
Vaccines 2020, 8(4), 624; https://doi.org/10.3390/vaccines8040624 - 25 Oct 2020
Cited by 1 | Viewed by 689
Abstract
Neisseria meningitidis is often asymptomatically carried in the nasopharynx but may cause invasive meningococcal disease, leading to morbidity and mortality. Meningococcal conjugate vaccinations induce functional protective antibodies against capsular antigens, but seroprotection wanes over time. We measured functional antibody titers five years after [...] Read more.
Neisseria meningitidis is often asymptomatically carried in the nasopharynx but may cause invasive meningococcal disease, leading to morbidity and mortality. Meningococcal conjugate vaccinations induce functional protective antibodies against capsular antigens, but seroprotection wanes over time. We measured functional antibody titers five years after administration of a single dose of the meningococcal ACWY-polysaccharide-specific tetanus toxoid-conjugated (MenACWY-TT) vaccine in adolescents and middle-aged adults in the Netherlands, using the serum bactericidal antibody with baby rabbit complement (rSBA) assay. Protection was defined as rSBA titer ≥8. The meningococcal ACWY-specific serum IgG concentrations were measured with a multiplex immunoassay. Duration of protection was estimated by a bi-exponential decay model. Sufficient protection for MenC, MenW, and MenY was achieved in 94–96% of the adolescents five years postvaccination, but, in middle-aged adults, only in 32% for MenC, 65% for MenW and 71% for MenY. Median duration of protection for MenCWY was 4, 14, and 21 years, respectively, in middle-aged adults, while, in adolescents, it was 32, 98, and 33 years. Our findings suggest that adolescents, primed in early childhood with MenC conjugate vaccination, remain sufficiently protected after a single dose of MenACWY-TT vaccine. Middle-aged adults without priming vaccination show fast waning of antibodies, particularly MenC, for which protection is lost after four years. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
The Combination of Molecular Adjuvant CCL35.2 and DNA Vaccine Significantly Enhances the Immune Protection of Carassius auratus gibelio against CyHV-2 Infection
Vaccines 2020, 8(4), 567; https://doi.org/10.3390/vaccines8040567 - 01 Oct 2020
Cited by 3 | Viewed by 753
Abstract
Cyprinid herpesvirus 2 (CyHV-2) infection results in huge economic losses in gibel carp (Carassius auratus gibelio) industry. In this study, we first constructed recombinant plasmids pcORF25 and pcCCL35.2 as DNA vaccine and molecular adjuvant against CyHV-2, respectively, and confirmed that both [...] Read more.
Cyprinid herpesvirus 2 (CyHV-2) infection results in huge economic losses in gibel carp (Carassius auratus gibelio) industry. In this study, we first constructed recombinant plasmids pcORF25 and pcCCL35.2 as DNA vaccine and molecular adjuvant against CyHV-2, respectively, and confirmed that both recombinant plasmids could be effectively expressed in vitro and in vivo. Then, the vaccination and infection experiments (n = 50) were set as seven groups. The survival rate (70%) in ORF25/CCL35.2 group was highest. The highest specific antibody levels were found in ORF25/CCL35.2 group in major immune tissues by qRT-PCR, and confirmed in serum by ELISA assay, antibody neutralization titer, and serum incubation-infection experiments. Three crucial innate immune indices, namely C3 content, lysozyme, and total superoxide dismutase (TSOD) activities, were highest in ORF25/CCL35.2 group in serum. pcORF25/pcCCL35.2 can effectively up-regulate mRNA expressions of some important immune genes (IL-1β, IL-2, IFN-γ2, and viperin), and significantly suppress CyHV-2 replication in head kidney and spleen tissues. The minimal tissue lesions can be seen in ORF25/CCL35.2 group in gill, spleen, and trunk kidney tissues by histopathological examination. The results indicated that the combination of DNA vaccine pcORF25 and molecular adjuvant pcCCL35.2 is an effective method against CyHV-2 infection, suggesting a feasible strategy for the control of fish viral diseases. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Development of a Recombinant Thermostable Newcastle Disease Virus (NDV) Vaccine Express Infectious Bronchitis Virus (IBV) Multiple Epitopes for Protecting against IBV and NDV Challenges
Vaccines 2020, 8(4), 564; https://doi.org/10.3390/vaccines8040564 - 01 Oct 2020
Viewed by 900
Abstract
Newcastle disease (ND) and infectious bronchitis (IB) are two highly contagious diseases that severely threaten the poultry industry. The goal of this study is to prevent these two diseases and reduce the vaccine costs during storage and transportation. In this study, we design [...] Read more.
Newcastle disease (ND) and infectious bronchitis (IB) are two highly contagious diseases that severely threaten the poultry industry. The goal of this study is to prevent these two diseases and reduce the vaccine costs during storage and transportation. In this study, we design a thermostable recombinant Newcastle disease virus (NDV) candidate live vaccine strain designated as rLS-T-HN-T/B, which expresses the multiple epitope cassette of the identified infectious bronchitis virus (IBV) (S-T/B). The rLS-T-HN-T/B strain was found to possess similar growth kinetics, passage stability, morphological characteristics, and virulence to the parental LaSota strain. After incubation at 56 °C at the indicated time points, the rLS-T-HN-T/B strain was determined by the hemagglutination (HA), and 50% embryo infectious dose (EID50) assays demonstrated that it accords with the criteria for thermostability. The thermostable rLS-T-HN-T/B and parental LaSota vaccines were stored at 25 °C for 16 days prior to immunizing the one-day-old specific pathogen-free (SPF) chicks. Three weeks postimmunization, the virus challenge results suggested that the chicks vaccinated with the rLS-T-HN-T/B vaccine were protected by 100% and 90% against a lethal dose of NDV and IBV, respectively. Furthermore, the trachea ciliary activity assay indicated that the mean ciliostasis score of the chicks vaccinated with thermostable rLS-T-HN-T/B vaccine was significantly superior to that of the LaSota and PBS groups (p < 0.05). The rLS-T-HN-T/B vaccine stored at 25 °C for 16 days remained capable of eliciting the immune responses and protecting against IBV and NDV challenges. However, the same storage conditions had a great impact on the parental LaSota strain vaccinated chicks, and the NDV challenge protection ratio was only 20%. We conclude that the thermostable rLS-T-HN-T/B strain is a hopeful bivalent candidate vaccine to control both IB and ND and provides an alternative strategy for the development of cost-effective vaccines for village chickens, especially in the rural areas of developing countries. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Antibody Response to Canine Parvovirus Vaccination in Dogs with Hyperadrenocorticism Treated with Trilostane
Vaccines 2020, 8(3), 547; https://doi.org/10.3390/vaccines8030547 - 19 Sep 2020
Cited by 5 | Viewed by 1125
Abstract
It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs [...] Read more.
It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs with HAC, and healthy age-matched control dogs (n = 31) received a modified-live CPV vaccine. Antibodies were determined on days 0, 7, and 28 by hemagglutination inhibition. Univariate analysis was used to compare the immune response of dogs with HAC and healthy dogs. Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HAC (11/11; 95% CI: 70.0–100) and in 93.5% of healthy dogs (29/31; 95% CI: 78.3–99.2). No ≥4-fold increase in antibody titer was observed in dogs with HAC while in 22.6% of healthy dogs, a ≥4-fold titer increase was observed (7/31; 95% CI: 11.1–40.1). Mild vaccine-associated adverse events (VAAEs) were detected in 54.5% of dogs with HAC (6/11; 95% CI: 28.0–78.8) and in 29.0% of healthy dogs (9/31; 95% CI: 15.9–46.8). There was neither a significant difference in presence of pre-vaccination antibodies (p = 1.000), or response to vaccination (p = 0.161), nor in the occurrence of VAAEs (p = 0.158). Immune function of dogs with HAC treated with trilostane seems comparable to that of healthy dogs. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
Article
Kinetics of Anti-Hepatitis B Surface Antigen Titers in Nurse Students after a Two-Year Follow-Up
Vaccines 2020, 8(3), 467; https://doi.org/10.3390/vaccines8030467 - 21 Aug 2020
Viewed by 989
Abstract
Infection caused by hepatitis B virus (HBV) can be prevented through a safe and effective vaccine. This study analysed the kinetics of serum antibodies against hepatitis B surface antigen (HBsAg) (anti-HBs) titers in relation to previous vaccine boosters in Italian nursing students who [...] Read more.
Infection caused by hepatitis B virus (HBV) can be prevented through a safe and effective vaccine. This study analysed the kinetics of serum antibodies against hepatitis B surface antigen (HBsAg) (anti-HBs) titers in relation to previous vaccine boosters in Italian nursing students who were followed up for two years. Serum anti-HBs titers were evaluated at the first visit, after vaccine booster (if required) and at visit after two years. Overall, 483 students (mean age = 21.7 years; SD = 3.7) with median anti-HBs IgG titer of 6 mUI/mL (interquartile range (IQR) = 0–34) were enrolled. A total of 254 (52.5%) students with a titer lower than 10 mIU/mL were offered an anti-HBV booster at the first visit. Among these students, an exponential relation between anti-HBs IgG titer, one month after HBV booster and anti-HBs IgG titer two years later was found (y = 3.32 exp (0.0045x); R2 = 0.48; p < 0.001). Students with anti-HBV titer higher than 10 mIU/mL (N = 229) were followed up, and anti-HBs IgG titers at follow-up visit linearly correlated with anti-HBV baseline titers (y = 0.86x + 26.2; R2 = 0.67; p < 0.001). A decrease in anti-HBs titers can be expected a few years after the anti-HBV booster dose. This reduction is more pronounced than that observed in students not administered the booster dose and is exponential with respect to basal titers assessed after the booster dose. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Hepatitis E Virus Mediates Renal Injury via the Interaction between the Immune Cells and Renal Epithelium
Vaccines 2020, 8(3), 454; https://doi.org/10.3390/vaccines8030454 - 14 Aug 2020
Cited by 10 | Viewed by 1114
Abstract
Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular [...] Read more.
Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion: The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures
Vaccines 2020, 8(3), 398; https://doi.org/10.3390/vaccines8030398 - 20 Jul 2020
Cited by 2 | Viewed by 678
Abstract
The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is [...] Read more.
The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Replication of Hepatitis E Virus (HEV) in Primary Human-Derived Monocytes and Macrophages In Vitro
Vaccines 2020, 8(2), 239; https://doi.org/10.3390/vaccines8020239 - 21 May 2020
Cited by 13 | Viewed by 1515
Abstract
HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not [...] Read more.
HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Article
Tropomyosin: An Excretory/Secretory Protein from Haemonchus contortus Mediates the Immuno-Suppressive Potential of Goat Peripheral Blood Mononuclear Cells In Vitro
Vaccines 2020, 8(1), 109; https://doi.org/10.3390/vaccines8010109 - 01 Mar 2020
Cited by 2 | Viewed by 1007
Abstract
During host-parasite interactions, binding of excretory/secretory proteins (ESPs) on the host immune cells is considered the fundamental phase for regulation of immune responses. In this study, gene encoding Haemonchus contortus tropomyosin (Hc-TpMy), was successfully cloned and expressed, and the recombinant protein after host [...] Read more.
During host-parasite interactions, binding of excretory/secretory proteins (ESPs) on the host immune cells is considered the fundamental phase for regulation of immune responses. In this study, gene encoding Haemonchus contortus tropomyosin (Hc-TpMy), was successfully cloned and expressed, and the recombinant protein after host cell surface attachment was evaluated for immune functional analysis with goat peripheral blood mononuclear cells (PBMCs) in vitro. The isopropyl-β-D-thiogalactopyranoside (IPTG)-induced recombinant protein was successfully recognized by the sera of rat experimentally infected with rHc-TpMy. The immunofluorescence assay detected attachment of rHc-TpMy on the surface of host PBMCs. Furthermore, immunoregulatory roles of rHc-TpMy on cytokines expression, PBMC proliferation, migration, nitric oxide (NO) production, apoptosis and monocytes phagocytosis were observed. The results showed that expression of IL-4 and IFN-γ cytokines, cell proliferation, NO production and PBMC migration were significantly suppressed by goat PBMCs after co-incubation with rHc-TpMy protein. However, the productions of IL-10, IL-17 and TGF-β1 cytokines, PBMCs apoptosis and monocytes phagocytosis were elevated at dose dependent manner. Our findings indicated that rHc-TpMy is an important ES binding protein exhibit distinct immuno-suppressive roles on goat PBMCs which might be a potential molecular target to control haemonchosis in future. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Review

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Review
Advances in the Development of Anti-Haemonchus contortus Vaccines: Challenges, Opportunities, and Perspectives
Vaccines 2020, 8(3), 555; https://doi.org/10.3390/vaccines8030555 - 22 Sep 2020
Cited by 5 | Viewed by 1741
Abstract
The gastrointestinal nematode parasite Haemonchus contortus (H. contortus) is a resident of tropical and subtropical regions worldwide that imposes significant production losses, economic losses, and animal health issues in the small ruminant industry, particularly sheep and goats. Considerable efforts have been [...] Read more.
The gastrointestinal nematode parasite Haemonchus contortus (H. contortus) is a resident of tropical and subtropical regions worldwide that imposes significant production losses, economic losses, and animal health issues in the small ruminant industry, particularly sheep and goats. Considerable efforts have been made to understand how immunity is elicited against H. contortus infection. Various potential vaccine antigens have been tested by different methods and strategies applied in animal models, and significant progress has been made in the development of vaccines against H. contortus. This review highlighted and shared the knowledge about the current understanding of host immune responses to H. contortus and ongoing challenges in the development of a protective, effective, and long-lasting vaccine against H. contortus infection. We have also pinpointed some achievements and failures in the development and testing of vaccines, which will establish a road map for future research directions to explore new effective vaccine candidates for controlling and preventing H. contortus infection. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Review
Influenza–Host Interplay and Strategies for Universal Vaccine Development
Vaccines 2020, 8(3), 548; https://doi.org/10.3390/vaccines8030548 - 20 Sep 2020
Cited by 3 | Viewed by 1677
Abstract
Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus [...] Read more.
Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus hemagglutinin (HA) glycoprotein that binds to the cellular sialic acid receptors and facilitates the fusion of the viral membrane with the endosomal membrane. During IAV infection, virus-derived pathogen-associated molecular patterns (PAMPs) are recognized by host intracellular specific sensors including toll-like receptors (TLRs), C-type lectin receptors, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) either on the cell surface or intracellularly in endosomes. Herein, we comprehensively review the current knowledge available on the entry of the influenza virus into host cells and the molecular details of the influenza virus–host interface. We also highlight certain strategies for the development of universal influenza vaccines. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Review
Role of Opsonophagocytosis in Immune Protection against Malaria
Vaccines 2020, 8(2), 264; https://doi.org/10.3390/vaccines8020264 - 30 May 2020
Cited by 1 | Viewed by 1017
Abstract
The quest for immune correlates of protection continues to slow vaccine development. To date, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that [...] Read more.
The quest for immune correlates of protection continues to slow vaccine development. To date, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that the quantitative assessment of antibody responses alone often fails to correlate with protective immunity or vaccine efficacy. Despite these limitations, the simple measurement of post-vaccination antibody titers remains the most widely used approaches for vaccine evaluation. Developing and performing functional assays to assess the biological activity of pathogen-specific responses continues to gain momentum; integrating serological assessments with functional data will ultimately result in the identification of mechanisms that contribute to protective immunity and will guide vaccine development. One of these functional readouts is phagocytosis of antigenic material tagged by immune molecules such as antibodies and/or complement components. This review summarizes our current understanding of how phagocytosis contributes to immune defense against pathogens, the pathways involved, and defense mechanisms that pathogens have evolved to deal with the threat of phagocytic removal and destruction of pathogens. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
Review
Dynamics of Population Immunity Due to the Herd Effect in the COVID-19 Pandemic
Vaccines 2020, 8(2), 236; https://doi.org/10.3390/vaccines8020236 - 19 May 2020
Cited by 33 | Viewed by 5522
Abstract
The novel Coronavirus 2 Severe Acute Respiratory Syndrome (SARS-Cov-2) has led to the Coronavirus Disease 2019 (COVID-19) pandemic, which has surprised health authorities around the world, quickly producing a global health crisis. Different actions to cope with this situation are being developed, including [...] Read more.
The novel Coronavirus 2 Severe Acute Respiratory Syndrome (SARS-Cov-2) has led to the Coronavirus Disease 2019 (COVID-19) pandemic, which has surprised health authorities around the world, quickly producing a global health crisis. Different actions to cope with this situation are being developed, including confinement, different treatments to improve symptoms, and the creation of the first vaccines. In epidemiology, herd immunity is presented as an area that could also solve this new global threat. In this review, we present the basis of herd immunology, the dynamics of infection transmission that induces specific immunity, and how the application of immunoepidemiology and herd immunology could be used to control the actual COVID-19 pandemic, along with a discussion of its effectiveness, limitations, and applications. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Review
Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19
Vaccines 2020, 8(2), 224; https://doi.org/10.3390/vaccines8020224 - 14 May 2020
Cited by 26 | Viewed by 4290
Abstract
As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition [...] Read more.
As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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Case Report
Pneumocystis jirevocii and SARS-CoV-2 Co-Infection: A Common Feature in Transplant Recipients?
Vaccines 2020, 8(3), 544; https://doi.org/10.3390/vaccines8030544 - 18 Sep 2020
Cited by 7 | Viewed by 1207
Abstract
COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the [...] Read more.
COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the prognosis and the severity of the disease, and can in turn lead to an increased need of mechanical ventilation, antibiotic therapy and to a higher mortality. Here we describe, for the first time in Europe, a fatal case of co-infection between SARS-CoV-2 and Pneumocystis jirevocii in a kidney transplant recipient. Full article
(This article belongs to the Special Issue Infectious Diseases Immunology)
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