Research

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17 pages, 2310 KiB

Open AccessArticle

A Fermented Milk Matrix Containing Postbiotics Supports Th1- and Th17-Type Immunity In Vitro and Modulates the Influenza-Specific Vaccination Response In Vivo in Association with Altered Serum Galectin Ratios

by Veronica Ayechu-Muruzabal, Ling Xiao, Tjalling Wehkamp, Ingrid van Ark, Elisabeth J. Hoogendoorn, Thea Leusink-Muis, Gert Folkerts, Johan Garssen, Linette E. M. Willemsen and Belinda van’t Land

Vaccines 2021, 9(3), 254; https://doi.org/10.3390/vaccines9030254 - 13 Mar 2021

Cited by 6 | Viewed by 2461

Abstract

During a specific milk fermentation process with Bifidobacterium breve C50 and Streptococcus thermophilus 065 (Lactofidus^TM), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentation product (FP) in vitro using a model that allows crosstalk between intestinal [...] Read more.

During a specific milk fermentation process with Bifidobacterium breve C50 and Streptococcus thermophilus 065 (Lactofidus^TM), postbiotics with possible immunomodulatory properties are produced. We investigated the effects of this fermentation product (FP) in vitro using a model that allows crosstalk between intestinal epithelial (IEC) and immune cells. IECs were exposed to FP and αCD3/CD28-activated peripheral blood mononuclear cells after which the mediator secretion was measured. Additionally, using a murine influenza vaccination model, immune development was assessed. Mice were fed an AIN93G diet containing FP or lactose as control. Vaccine-specific immunity was measured as delayed-type hypersensitivity (DTH) and correlated to intestinal and systemic immunomodulation levels. In vitro, exposure to FP enhanced IFNγ, TNFα and IL-17A concentrations. Moreover, IEC-derived galectin-3/galectin-9 and galectin-4/galectin-9 ratios were increased. In vivo, dietary intervention with FP increased vaccine-specific DTH responses as compared to the lactose-receiving group. Although no effects on humoral immunity and vaccine-specific T-cell responses were detected, an enhanced systemic serum galectin-3/galectin-9 and galectin-4/galectin-9 ratio correlated with a shift in RORγ (Th17) mRNA expression over regulatory TGFβ1 in the ileum. This was also positively correlated with the increased DTH response. These results indicate that FP can enhance epithelial galectin-3 and -4 over galectin-9 release, and boost adaptive immunity by promoting Th1- and Th17-type cytokines under inflammatory conditions in vitro. Similar variations in galectin and immune balance were observed in the vaccination model, where FP improved the influenza-specific DTH response. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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20 pages, 2059 KiB

Open AccessArticle

Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy

by Mar Naranjo-Gomez, Marine Cahen, Jennifer Lambour, Myriam Boyer-Clavel and Mireia Pelegrin

Vaccines 2021, 9(2), 137; https://doi.org/10.3390/vaccines9020137 - 08 Feb 2021

Cited by 6 | Viewed by 2979

Abstract

Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this [...] Read more.

Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Importantly, functional NK cells play an essential role in preventing immune dysfunction and inducing antiviral protective immunity upon mAb therapy. Thus, NK cell depletion in mAb-treated, viral-infected mice leads to the upregulation of molecules involved in immunosuppressive pathways (i.e., PD-1, PD-L1 and CD39) on dendritic cells and T cells. NK cell depletion also abrogates the vaccinal effects induced by mAb therapy. Our data also reveal a role for IFNγ-producing NK cells in the enhancement of the B-cell responses through the potentiation of the B-cell helper properties of neutrophils. These findings suggest that preserved NK cell functions and counts might be required for achieving mAb-induced protective immunity. They open new prospects for improving antiviral immunotherapies. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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15 pages, 2170 KiB

Open AccessArticle

BCG Provides Short-Term Protection from Experimental Cerebral Malaria in Mice

by Julia Witschkowski, Jochen Behrends, Roland Frank, Lars Eggers, Linda von Borstel, David Hertz, Ann-Kristin Mueller and Bianca E. Schneider

Vaccines 2020, 8(4), 745; https://doi.org/10.3390/vaccines8040745 - 09 Dec 2020

Cited by 9 | Viewed by 3042

Abstract

Clinical and experimental evidence suggests that the tuberculosis vaccine BCG offers protection against unrelated pathogens including the malaria parasite. Cerebral malaria (CM) is the most severe complication associated with Plasmodium falciparum infection in humans and is responsible for most of the fatalities attributed [...] Read more.

Clinical and experimental evidence suggests that the tuberculosis vaccine BCG offers protection against unrelated pathogens including the malaria parasite. Cerebral malaria (CM) is the most severe complication associated with Plasmodium falciparum infection in humans and is responsible for most of the fatalities attributed to malaria. We investigated whether BCG protected C57BL/6 mice from P. berghei ANKA (PbA)-induced experimental CM (ECM). The majority of PbA-infected mice that were immunized with BCG showed prolonged survival without developing clinical symptoms of ECM. However, this protective effect waned over time and was associated with the recovery of viable BCG from liver and spleen. Intriguingly, BCG-mediated protection from ECM was not associated with a reduction in parasite burden, indicating that BCG immunization did not improve anti-parasite effector mechanisms. Instead, we found a significant reduction in pro-inflammatory mediators and CD8⁺ T cells in brains of BCG-vaccinated mice. Together these data suggest that brain recruitment of immune cells involved in the pathogenesis of ECM decreased after BCG vaccination. Understanding the mechanisms underlying the protective effects of BCG on PbA-induced ECM can provide a rationale for developing effective adjunctive therapies to reduce the risk of death and brain damage in CM. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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21 pages, 2478 KiB

Open AccessArticle

Mucosal Vaccination with Lactococcus lactis-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B Streptococcus in a Murine Model

by Diego A. Diaz-Dinamarca, Carlos Hernandez, Daniel F. Escobar, Daniel A. Soto, Guillermo A. Muñoz, Jesús F. Badilla, Ricardo A. Manzo, Flavio Carrión, Alexis M. Kalergis and Abel E. Vasquez

Vaccines 2020, 8(2), 146; https://doi.org/10.3390/vaccines8020146 - 26 Mar 2020

Cited by 18 | Viewed by 4433

Abstract

Group B Streptococcus (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed [...] Read more.

Group B Streptococcus (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. Lactococcus lactis is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant L. lactis strain secreting SIP from GBS (rL. lactis-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with rL. lactis-SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our rL. lactis-SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naïve mice generated protection against GBS vaginal colonization. Moreover, the rL. lactis-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that rL. lactis-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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18 pages, 3540 KiB

Open AccessArticle

Rapid and Broad Immune Efficacy of a Recombinant Five-Antigen Vaccine against Staphylococcus aureus Infection in Animal Models

by Hao Zeng, Feng Yang, Qiang Feng, Jinyong Zhang, Jiang Gu, Haiming Jing, Changzhi Cai, Liming Xu, Xi Yang, Xin Xia, Ni Zeng, Shaowen Fan and Quanming Zou

Vaccines 2020, 8(1), 134; https://doi.org/10.3390/vaccines8010134 - 18 Mar 2020

Cited by 34 | Viewed by 5944

Abstract

Staphylococcus aureus (S. aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. Developing an efficacious vaccine against S. aureus is urgently required. In the present study, we selected five [...] Read more.

Staphylococcus aureus (S. aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. Developing an efficacious vaccine against S. aureus is urgently required. In the present study, we selected five conserved antigens, including the secreted factors α-hemolysin (Hla), staphylococcal enterotoxin B (SEB) and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC). They were all well-characterized virulence factor of S. aureus and developed a recombinant five-antigen S. aureus vaccine (rFSAV), rFSAV provided consistent protection in S. aureus lethal sepsis and pneumonia mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S. aureus strains. Meanwhile, rFSAV immunized mice were able to induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus. Moreover, the importance of specific antibodies in protection was demonstrated by antibody function tests in vitro and in vivo. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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17 pages, 3987 KiB

Open AccessArticle

Targeted Delivery of Mannosylated Nanoparticles Improve Prophylactic Efficacy of Immersion Vaccine against Fish Viral Disease

by Bin Zhu, Chen Zhang, Zhao Zhao and Gao-Xue Wang

Vaccines 2020, 8(1), 87; https://doi.org/10.3390/vaccines8010087 - 15 Feb 2020

Cited by 30 | Viewed by 4467

Abstract

Immersion vaccination is considered as the most effective method for juvenile fish in preventing viral disease, due to its convenience for mass vaccination and stress-free administration. However, immune responses following immersion vaccination are generally less robust and of shorter duration than those induced [...] Read more.

Immersion vaccination is considered as the most effective method for juvenile fish in preventing viral disease, due to its convenience for mass vaccination and stress-free administration. However, immune responses following immersion vaccination are generally less robust and of shorter duration than those induced through intraperitoneal injection. Herein, to improve the efficacy of the immersion vaccine, we constructed a targeted single-walled carbon nanotubes-based immersion vaccine delivery system (CNTs-M-VP7), the surface of which are modified with mannose to allow antigen-presenting cells’ (APCs) targeting. The targeting ability of CNTs-M-VP7 was confirmed in vivo and in vitro. Critically, this immersion CNTs-M-VP7 vaccine could cross into the fish body through mucosal tissues (skin, gill, and intestine), and then present to immune-related tissues. Moreover, CNTs-M-VP7 could significantly induce the maturation and presenting process of APCs, which would then trigger robust immune responses. Altogether, this study demonstrates that the single-walled carbon nanotubes (SWCNTs)-based targeted nanovaccine delivery system shows the potential to be an effective prophylactic against fish viral disease. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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14 pages, 1034 KiB

Open AccessArticle

Evaluation of the Immunoprotective Potential of Recombinant Paraflagellar Rod Proteins of Trypanosoma evansi in Mice

by Biswa Ranjan Maharana, Naduvanahalli Rajanna Sudhakar, Vijayakumar Jawalagatti, Buddhi Chandrasekaran Saravanan, Damer P Blake and Anup Kumar Tewari

Vaccines 2020, 8(1), 84; https://doi.org/10.3390/vaccines8010084 - 12 Feb 2020

Cited by 5 | Viewed by 3169

Abstract

Trypanosomosis, caused by Trypanosoma evansi, is an economically significant disease of livestock. Systematic antigenic variation by the parasite has undermined prospects for the development of a protective vaccine that targets the immunodominant surface antigens, encouraging exploration of alternatives. The paraflagellar rod (PFR), [...] Read more.

Trypanosomosis, caused by Trypanosoma evansi, is an economically significant disease of livestock. Systematic antigenic variation by the parasite has undermined prospects for the development of a protective vaccine that targets the immunodominant surface antigens, encouraging exploration of alternatives. The paraflagellar rod (PFR), constituent proteins of the flagellum, are prominent non-variable vaccine candidates for T. evansi owing to their strategic location. Two major PFR constituent proteins, PFR1 (1770bp) and PFR2 (1800bp), were expressed using Escherichia coli. Swiss albino mice were immunized with the purified recombinant TePFR1 (89KDa) and TePFR2 (88KDa) proteins, as well as with the mix of the combined proteins at equimolar concentrations, and subsequently challenged with virulent T. evansi. The PFR-specific humoral response was assessed by ELISA. Cytometric bead-based assay was used to measure the cytokine response and flow cytometry for quantification of the cytokines. The recombinant TePFR proteins induced specific humoral responses in mice, including IgG1 followed by IgG2a and IgG2b. A balanced cytokine response induced by rTePFR 1 and 2 protein vaccination associated with extended survival and improved control of parasitemia following lethal challenge. The observation confirms the immunoprophylactic potential of the covert antigens of T. evansi. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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13 pages, 4361 KiB

Open AccessArticle

Protective Immunity Elicited by VP1 Chimeric Antigens of Bacterial Ghosts against Hand-Foot-and-Mouth Disease Virus

by Saisai Gong, Nan Nan, Yakun Sun, Zhili He, Jiajia Li, Fanghong Chen, Tao Li, Nianzhi Ning, Jianxin Wang, Zhan Li, Deyan Luo and Hui Wang

Vaccines 2020, 8(1), 61; https://doi.org/10.3390/vaccines8010061 - 01 Feb 2020

Cited by 11 | Viewed by 2678

Abstract

This study was designed to evaluate the immunogenicity and protective efficacy of two VP1 chimeric antigens of bacterial ghosts. Inoculation of the two VP1 chimeric antigens of bacterial ghosts into BALB/c mice markedly elicited humoral and mucosal immune responses. The specific antibodies induced [...] Read more.

This study was designed to evaluate the immunogenicity and protective efficacy of two VP1 chimeric antigens of bacterial ghosts. Inoculation of the two VP1 chimeric antigens of bacterial ghosts into BALB/c mice markedly elicited humoral and mucosal immune responses. The specific antibodies induced by the chimeric ghosts protected mice not only against the virus that causes hand-foot-and-mouth disease but also against E. coli O157:H7 bacterial infection. In comparison with the negative control, immunization with the chimeric ghosts protected mice against two LD₅₀ hand-foot-and-mouth disease viral infection. In addition, this specific immunity also protected the pups of pregnant mice immunized with the VP1 chimeric antigens of bacterial ghosts against 20 MLD E. coli O157:H7 infection. Taken together, the results of this study verify for the first time that the VP1 chimeric antigens of bacterial ghosts are target candidates for a new type of vaccine against hand-foot-and-mouth disease. Additionally, this vaccine strategy also elicited a stronger immune response against E. coli O157:H7. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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Review

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9 pages, 209 KiB

Open AccessEditor’s ChoiceReview

Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin

by Claudio Costantini, Frank L. van de Veerdonk and Luigina Romani

Vaccines 2020, 8(4), 713; https://doi.org/10.3390/vaccines8040713 - 01 Dec 2020

Cited by 23 | Viewed by 3903

Abstract

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor in the clinical presentation of COVID-19, which may range from asymptomatic to a fatal, multi-organ disease. A dysregulated immune response not only compromises the ability of the host [...] Read more.

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical factor in the clinical presentation of COVID-19, which may range from asymptomatic to a fatal, multi-organ disease. A dysregulated immune response not only compromises the ability of the host to resolve the viral infection, but may also predispose the individual to secondary bacterial and fungal infections, a risk to which the current therapeutic immunomodulatory approaches significantly contribute. Among the secondary infections that may occur in COVID-19 patients, coronavirus-associated pulmonary aspergillosis (CAPA) is emerging as a potential cause of morbidity and mortality, although many aspects of the disease still remain unresolved. With this opinion, we present the current view of CAPA and discuss how the same mechanisms that underlie the dysregulated immune response in COVID-19 increase susceptibility to Aspergillus infection. Likewise, resorting to endogenous pathways of immunomodulation may not only restore immune homeostasis in COVID-19 patients, but also reduce the risk for aspergillosis. Therefore, CAPA represents the other side of the coin in COVID-19 and our advances in the understanding and treatment of the immune response in COVID-19 should represent the framework for the study of CAPA. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

15 pages, 871 KiB

Open AccessReview

Immune System Modulations by Products of the Gut Microbiota

by Thierry Chénard, Karine Prévost, Jean Dubé and Eric Massé

Vaccines 2020, 8(3), 461; https://doi.org/10.3390/vaccines8030461 - 21 Aug 2020

Cited by 19 | Viewed by 3592

Abstract

The gut microbiota, which consists of all bacteria, viruses, fungus, and protozoa living in the intestine, and the immune system have co-evolved in a symbiotic relationship since the origin of the immune system. The bacterial community forming the microbiota plays an important role [...] Read more.

The gut microbiota, which consists of all bacteria, viruses, fungus, and protozoa living in the intestine, and the immune system have co-evolved in a symbiotic relationship since the origin of the immune system. The bacterial community forming the microbiota plays an important role in the regulation of multiple aspects of the immune system. This regulation depends, among other things, on the production of a variety of metabolites by the microbiota. These metabolites range from small molecules to large macro-molecules. All types of immune cells from the host interact with these metabolites resulting in the activation of different pathways, which result in either positive or negative responses. The understanding of these pathways and their modulations will help establish the microbiota as a therapeutic target in the prevention and treatment of a variety of immune-related diseases. Full article

(This article belongs to the Special Issue Our Immune System Is the First Line of Defense towards Infections: Modulation of the Immune System to Boost the Host Defense Response towards Pathogens)

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