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Vaccines
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Non-specific Protections in Response to Vaccination and Other Stimulations of...
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Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Pathogens-host Immune Interface".

Deadline for manuscript submissions: closed (18 February 2023) | Viewed by 15733

Special Issue Editors

Dr. François Meurens

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Guest Editor
Swine and Poultry Infectious Diseases Research Center (CRIPA), Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada
Interests: virology; veterinary microbiology; innate immune response; animal model; pig; vaccines; mucosal immunology; respiratory and intestinal infectious diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Fanny Renois

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Guest Editor
BIOEPAR, INRAE, Oniris, 44307 Nantes, France
Interests: viral infection; viral immunology; apoptosis; immunology of infectious diseases; molecular virology; virology; cell culture; microbiology; vaccination; virus
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jianzhong Zhu

E-Mail Website
Guest Editor
College Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
Interests: infection and immunity; innate immune signaling; comparative immunology; anti-viral immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the era of coronavirus disease 2019 (COVID-19) and antimicrobial resistance, vaccination is more than ever the best way to protect against various infectious diseases. Based on previous observations and recent exciting research, some strong evidence also shows that immune stimulation through vaccination, as well as microbial and non-microbial stimuli, can alter the immune system in such a way that it also increases immune protections against unrelated pathogens. These are the so-called “non-specific effects” (NSEs). Recently, NSEs involving the training of the innate defenses known as “trained immunity” have been the subject of many studies in humans and other species, including livestock. In the current Special Issue, all original studies and reviews presenting research in relation with NSE and particularly trained immunity in humans and domestic species are welcome. Please do not hesitate to submit.

Prof. Dr. François Meurens
Dr. Fanny Renois
Prof. Dr. Jianzhong Zhu
Guest Editors

Manuscript Submission Information

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

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 2700 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

  • Non-Specific Protections
  • vaccination
  • non-specific effects (NSEs)
  • trained immunity
  • immune system
  • pathogens

Related Special Issue

Published Papers (6 papers)

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Research

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18 pages, 3630 KiB  
Article
Plant-Produced Mouse-Specific Zona Pellucida 3 Peptide Induces Immune Responses in Mice
by Khadijeh Ghasemian, Inge Broer, Jennifer Schön, Nadine Kolp, Richard Killisch and Jana Huckauf
Vaccines 2023, 11(1), 153; https://doi.org/10.3390/vaccines11010153 - 10 Jan 2023
Cited by 2 | Viewed by 1528
Abstract
Contraceptive vaccines are designed to stimulate autoimmune responses to molecules involved in the reproductive process. A mouse-specific peptide from zona pellucida 3 (mZP3) has been proposed as a target epitope. Here, we employed a plant expression system for the production of glycosylated mZP3 [...] Read more.
Contraceptive vaccines are designed to stimulate autoimmune responses to molecules involved in the reproductive process. A mouse-specific peptide from zona pellucida 3 (mZP3) has been proposed as a target epitope. Here, we employed a plant expression system for the production of glycosylated mZP3 and evaluated the immunogenicity of plant-produced mZP3-based antigens in a female BALB/c mouse model. In the mZP3-1 antigen, mZP3 fused with a T-cell epitope of tetanus toxoid, a histidine tag, and a SEKDEL sequence. A fusion antigen (GFP-mZP3-1) and a polypeptide antigen containing three repeats of mZP3 (mZP3-3) were also examined. Glycosylation of mZP3 should be achieved by targeting proteins to the endoplasmic reticulum. Agrobacterium-mediated transient expression of antigens resulted in successful production of mZP3 in Nicotiana benthamiana. Compared with mZP3-1, GFP-mZP3-1 and mZP3-3 increased the production of the mZP3 peptide by more than 20 and 25 times, respectively. The glycosylation of the proteins was indicated by their size and their binding to a carbohydrate-binding protein. Both plant-produced GFP-mZP3-1 and mZP3-3 antigens were immunogenic in mice; however, mZP3-3 generated significantly higher levels of serum antibodies against mZP3. Induced antibodies recognized native zona pellucida of wild mouse, and specific binding of antibodies to the oocytes was observed in immunohistochemical studies. Therefore, these preliminary results indicated that the plants can be an efficient system for the production of immunogenic mZP3 peptide, which may affect the fertility of wild mice. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)
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12 pages, 918 KiB  
Article
Early Activation of the Innate Immunity and Specific Cellular Immune Pathways after Vaccination with a Live Intranasal Viral Vaccine and Challenge with Bovine Parainfluenza Type 3 Virus
by Piet Nuijten, Natalie Cleton, Jeroen van der Loop, Birgit Makoschey, Wilco Pulskens and Geert Vertenten
Vaccines 2022, 10(1), 104; https://doi.org/10.3390/vaccines10010104 - 11 Jan 2022
Cited by 3 | Viewed by 1737
Abstract
Bovine parainfluenza type 3 (BPIV3) and bovine respiratory syncytial virus (BRSV) may cause bovine respiratory disease (BRD) in very young calves, and therefore vaccination should induce protection at the youngest age and as quickly as possible. This can be achieved by intranasal vaccination [...] Read more.
Bovine parainfluenza type 3 (BPIV3) and bovine respiratory syncytial virus (BRSV) may cause bovine respiratory disease (BRD) in very young calves, and therefore vaccination should induce protection at the youngest age and as quickly as possible. This can be achieved by intranasal vaccination with a vaccine containing live attenuated BRSV and BPIV3 virus strains. The objective of this study was to measure gene expression levels by means of RT-qPCR of proteins involved in the innate and adaptive immune response in the nasopharyngeal mucosae after administration of the above-mentioned vaccine and after challenge with BPIV3. Gene expression profiles were different between (i) vaccinated, (ii) nonvaccinated-challenged, and (iii) vaccinated-challenged animals. In nonvaccinated-challenged animals, expression of genes involved in development of disease symptoms and pathology were increased, however, this was not the case after vaccination. Moreover, gene expression patterns of vaccinated animals reflected induction of the antiviral and innate immune pathways as well as an initial Th1 (cytotoxic) cellular response. After challenge with BPIV3, the vaccinated animals were protected against nasal shedding of the challenge virus and clinical symptoms, and in parallel the expression levels of the investigated genes had returned to values that were found before vaccination. In conclusion, in comparison to the virulent wild-type field isolates, the two virus strains in the vaccine have lost their capacity to evade the immune response, resulting in the induction of an antiviral state followed by a very early activation of innate immune and antiviral responses as well as induction of specific cellular immune pathways, resulting in protection. The exact changes in the genomes of these vaccine strains leading to attenuation have not been identified. These data represent the real-life situation and can serve as a basis for further detailed research. This is the first report describing the effects on immune gene expression profiles in the nasal mucosae induced by intranasal vaccination with a bivalent, live BRSV-BPI3V vaccine formulation in comparison to wild-type infection with a virulent BPI3V strain. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)
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15 pages, 14031 KiB  
Article
Screening of Porcine Innate Immune Adaptor Signaling Revealed Several Anti-PRRSV Signaling Pathways
by Yulin Xu, Mengxue Ye, Youwen Zhang, Shaohua Sun, Jia Luo, Sen Jiang, Jiajia Zhang, Xueliang Liu, Qi Shao, Qi Cao, Wanglong Zheng, François Meurens, Nanhua Chen and Jianzhong Zhu
Vaccines 2021, 9(10), 1176; https://doi.org/10.3390/vaccines9101176 - 14 Oct 2021
Cited by 5 | Viewed by 2115
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) causes PRRS and is known to effectively suppress host innate immunity. The current strategies for controlling PRRSV are limited and complete understanding of anti-PRRSV innate immunity is needed. Here, we utilized nine porcine innate immune signaling [...] Read more.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes PRRS and is known to effectively suppress host innate immunity. The current strategies for controlling PRRSV are limited and complete understanding of anti-PRRSV innate immunity is needed. Here, we utilized nine porcine innate immune signaling adaptors which represent all currently known innate immune receptor signaling pathways for screening of anti-PRRSV activity. The analysis of PRRSV N gene transcription and protein expression both suggested that the multiple ectopic adaptors exhibited varying degrees of anti-PRRSV activities, with TRIF and MAVS most effective. To better quantify the PRRSV replication, the GFP signal of PRRSV from reverse genetics were measured by flow cytometry and similarly varying anti-PRRSV activities by different signaling adaptors were observed. Based on the screening data, and considering the importance of viral nucleic acid in innate immune response, endogenous TRIF, MAVS and STING were selected for further examination of anti-PRRSV activity. Agonist stimulation assay showed that MAVS and STING signaling possessed significant anti-PRRSV activities, whereas siRNA knockdown assay showed that TRIF, MAVS and STING are all involved in anti-PRRSV activity, with TLR3-TRIF displaying discrepancy in anti-PRRSV infection. Nevertheless, our work suggests that multiple pattern recognition receptor (PRR) signaling pathways are involved in anti-PRRSV innate immunity, which may have implications for the development of future antiviral strategies. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)
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6 pages, 218 KiB  
Article
Oral Polio Vaccine Campaigns May Reduce the Risk of Death from Respiratory Infections
by Sebastian Nielsen, Hasan Mahmud Sujan, Christine Stabell Benn, Peter Aaby and Syed Manzoor Ahmed Hanifi
Vaccines 2021, 9(10), 1133; https://doi.org/10.3390/vaccines9101133 - 04 Oct 2021
Cited by 11 | Viewed by 2165
Abstract
Oral polio vaccine (OPV) campaigns, but not other campaigns, have been associated with major reductions in child mortality. Studies have shown that OPV reduces the risk of respiratory infections. We analysed the causes of death at 0–2 years of age in Chakaria, a [...] Read more.
Oral polio vaccine (OPV) campaigns, but not other campaigns, have been associated with major reductions in child mortality. Studies have shown that OPV reduces the risk of respiratory infections. We analysed the causes of death at 0–2 years of age in Chakaria, a health and demographic surveillance Systems in Bangladesh, in the period 2012–2019 where 13 national campaigns with combinations of OPV (n = 4), vitamin A supplementation (n = 9), measles vaccine (MV) (n = 2), and albendazole (n = 2) were implemented. OPV-only campaigns reduced overall mortality by 30% (95% confidence interval: −10–56%). Deaths from respiratory infections were reduced by 62% (20–82%, p = 0.01) in the post-neonatal period (1–35 months), whereas there was as slight increase of 19% (−37–127%, p = 0.54) for deaths from other causes. There was no benefit of other types of campaigns. Hence, the hypothesis that OPV may have beneficial non-specific effects, protecting particularly against respiratory infections, was confirmed. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)

Review

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10 pages, 798 KiB  
Review
Does Influenza Vaccination during Pregnancy Have Effects on Non-Influenza Infectious Morbidity? A Systematic Review and Meta-Analysis of Randomised Controlled Trials
by Katrine Pedersbæk Hansen, Christine Stabell Benn, Thomas Aamand, Martin Buus, Isaquel da Silva, Peter Aaby, Ane Bærent Fisker and Sanne Marie Thysen
Vaccines 2021, 9(12), 1452; https://doi.org/10.3390/vaccines9121452 - 08 Dec 2021
Cited by 2 | Viewed by 3662
Abstract
The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from [...] Read more.
The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from available randomised controlled trials (RCTs) of IIV to pregnant women, to assess whether IIV may have NSEs. Four RCTs, all conducted in low- and middle-income settings, were identified. We extracted information on all-cause and infectious mortality and adverse events in women and their infants. We conducted meta-analyses providing risk ratios (RR). The meta-analysis for maternal all-cause mortality provided a RR of 1.48 (95% CI = 0.52–4.16). The estimates for miscarriage/stillbirth and infant all-cause mortality up to 6 months of age were 1.06 (0.78–1.44) and 1.11 (0.87–1.41), respectively. IIV was associated with a higher risk of non-influenza infectious adverse events, with meta-estimates of 2.01 (1.15–3.50) in women and 1.36 (1.12–1.67) in infants up to 6 months of age. Thus, following a pattern seen for other non-live vaccines, IIV was associated with a higher risk of non-influenza infectious adverse events. To ensure that scarce resources are used well, and no harm is inflicted, further RCTs are warranted. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)
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Other

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18 pages, 1840 KiB  
Systematic Review
Non-Specific Effects of Bacillus Calmette-Guérin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Gerhard Trunk, Maša Davidović and Julia Bohlius
Vaccines 2023, 11(1), 121; https://doi.org/10.3390/vaccines11010121 - 04 Jan 2023
Cited by 5 | Viewed by 3491
Abstract
Background: Vaccines induce antigen-specific immunity, which provides long-lived protection from the target pathogen. Trials from areas with high incidence rates for infectious diseases indicated that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) induces in addition non-specific immunity against various pathogens and thereby reduces overall [...] Read more.
Background: Vaccines induce antigen-specific immunity, which provides long-lived protection from the target pathogen. Trials from areas with high incidence rates for infectious diseases indicated that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) induces in addition non-specific immunity against various pathogens and thereby reduces overall mortality more than would have been expected by just protecting from tuberculosis. Although recent trials produced conflicting results, it was suggested that BCG might protect from non-tuberculosis respiratory infections and could be used to bridge the time until a specific vaccine against novel respiratory diseases like COVID-19 is available. Methods: We performed a systematic search for randomized controlled trials (RCTs) published between 2011 and December 9th, 2022, providing evidence about non-specific effects after BCG vaccination, assessed their potential for bias, and meta-analyzed relevant clinical outcomes. We excluded RCTs investigating vaccination with an additional vaccine unless outcomes from a follow-up period before the second vaccination were reported. Results: Our search identified 16 RCTs including 34,197 participants. Vaccination with BCG caused an estimated 44% decrease in risk for respiratory infections (hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39–0.82) with substantial heterogeneity between trials (I2 = 77%). There was evidence for a protective effect on all-cause mortality of 21% if follow-up was restricted to one year (HR 0.79, 95% CI 0.64–0.99). We did not find evidence for an effect when we considered longer follow-up (HR 0.88, 95% CI 0.75–1.03). Infection-related mortality after BCG vaccination was reduced by 33% (HR 0.67; 95% CI 0.46–0.99), mortality for sepsis by 38% (HR 0.62, 95% CI 0.41–0.93). There was no evidence for a protective effect of BCG vaccination on infections of any origin (HR 0.84, 95% CI 0.71–1.00), COVID-19 (HR 0.88, 95% CI 0.68–1.14), sepsis (HR 0.78, 95% CI 0.55–1.10) or hospitalization (HR 1.01, 95% CI 0.91–1.11). Conclusions: According to these results, depending on the setting, vaccination with BCG provides time-limited partial protection against non-tuberculosis respiratory infections and may reduce mortality. These findings underline BCG’s potential (1) in pandemic preparedness against novel pathogens especially in developing countries with established BCG vaccination programs but limited access to specific vaccines; (2) in reducing microbial infections, antimicrobial prescriptions and thus the development of antimicrobial resistance. There is a need for additional RCTs to clarify the circumstances under which BCG’s non-specific protective effects are mediated. Full article
(This article belongs to the Special Issue Non-specific Protections in Response to Vaccination and Other Stimulations of the Immune System)
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