Research

16 pages, 2235 KiB

Open AccessArticle

Influenza B Virus (IBV) Immune-Mediated Disease in C57BL/6 Mice

by Harrison C. Bergeron, Zachary Beau Reneer, Aakash Arora, Stephen Reynolds, Tamas Nagy and Ralph A. Tripp

Vaccines 2022, 10(9), 1440; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10091440 - 01 Sep 2022

Cited by 5 | Viewed by 1826

Abstract

Influenza B viruses (IBV) primarily infect humans, causing seasonal epidemics. The absence of an animal reservoir limits pandemic concern, but IBV infections may cause severe respiratory disease, predominantly in young children and the elderly. The IBV disease burden is largely controlled by seasonal [...] Read more.

Influenza B viruses (IBV) primarily infect humans, causing seasonal epidemics. The absence of an animal reservoir limits pandemic concern, but IBV infections may cause severe respiratory disease, predominantly in young children and the elderly. The IBV disease burden is largely controlled by seasonal influenza vaccination; however, immunity due to vaccination is sometimes incomplete, a feature linked to antigenic mismatches. Thus, understanding the features that contribute to disease pathogenesis is important, particularly immune-mediated versus virus-mediated outcomes. Unexpectedly, C57BL/6 (B6) mice intranasally infected with a low multiplicity of infection of B/Florida/04/2006 developed substantial morbidity and mortality. To address the cause, B6 mice were treated daily with dexamethasone to dampen the immune and pro-inflammatory response to IBV infection, allowing the determination of whether the responses were immune- and/or virus-associated. As expected, dexamethasone (DEX)-treated mice had a lower pro-inflammatory response and reduced lung pathology despite the presence of high viral lung titers, but mortality was comparable to PBS-treated mice, indicating that mortality may be linked to lung virus replication. The results showed that the immune response to IBV is the major cause of morbidity, mortality, lung pathology, and viral clearance. Importantly, the results suggest that a robust lung CTL response and associated leukocyte influx contribute to disease. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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16 pages, 3393 KiB

Open AccessArticle

Assessment of In Vitro Immunostimulatory Activity of an Adjuvanted Whole-Cell Inactivated Neisseria gonorrhoeae Microparticle Vaccine Formulation

by Priyal Bagwe, Lotika Bajaj, Rikhav P. Gala, Martin J. D‘Souza and Susu M. Zughaier

Vaccines 2022, 10(7), 983; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10070983 - 21 Jun 2022

Cited by 5 | Viewed by 2136

Abstract

The emergence of drug-resistant gonorrhea infections worldwide combined with the lack of a vaccine is alarming. We prepared a novel microparticulate (MP) vaccine formulation using whole-cell inactivated Neisseria gonorrhoeae as the vaccine antigen, with Alum and AddaVax™ as vaccine adjuvants. The adjuvanted vaccine [...] Read more.

The emergence of drug-resistant gonorrhea infections worldwide combined with the lack of a vaccine is alarming. We prepared a novel microparticulate (MP) vaccine formulation using whole-cell inactivated Neisseria gonorrhoeae as the vaccine antigen, with Alum and AddaVax™ as vaccine adjuvants. The adjuvanted vaccine MP formulation was assessed for in vitro immunostimulatory activity, autophagy, and antigen presentation ability. The data shows that the adjuvanted gonococci vaccine MP enhanced autophagy induction in antigen presenting cells (APCs) compared to gonococci vaccine MP without adjuvants, which is important for enhancing antigen presentation. In addition, the adjuvanted vaccine formulation increased the surface expression of antigen presenting molecules MHCI and MHCII as well as co-stimulatory molecules CD40 and CD86 on the surface of dendritic cells. In addition, the gonococci vaccine microparticles at lower doses did not significantly increase the expression of the death receptor CD95 in APCs, which when elevated leads to suboptimal antigen presentation and reduced immune responses. The adjuvanted whole-cell inactivated gonococci microparticle vaccine formulation enhanced antigen uptake, processing, and antigen presentation. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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13 pages, 2733 KiB

Open AccessArticle

Immunodominant Linear B-Cell Epitopes of SARS-CoV-2 Spike, Identified by Sera from K18-hACE2 Mice Infected with the WT or Variant Viruses

by Yinon Levy, Ron Alcalay, Anat Zvi, Efi Makdasi, Eldar Peretz, Tal Noy-Porat, Theodor Chitlaru, Michal Mandelboim, Ohad Mazor and Ronit Rosenfeld

Vaccines 2022, 10(2), 251; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10020251 - 07 Feb 2022

Cited by 2 | Viewed by 1766

Abstract

SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the [...] Read more.

SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the spike protein in particular, may contribute to the development of sensitive diagnostic tools and identification of vaccine` candidate targets. In the current study, the anti-viral antibody response in transgenic K18-hACE-2 mice was examined by implementing an immunodominant epitope mapping approach of the SARS-CoV-2 spike. Serum samples for probing an epitope array covering the entire spike protein were collected from mice following infection with the original SARS-CoV-2 strain as well as the B.1.1.7 Alpha and B.1.351 Beta genetic variants of concern. The analysis resulted in distinction of six linear epitopes common to the humoral response against all virus variants inspected at a frequency of more than 20% of the serum samples. Finally, the universality of the response was probed by cross-protective in vitro experiments using plaque-reducing neutralization tests. The data presented here has important implications for prediction of the efficacy of immune countermeasures against emerging SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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14 pages, 2860 KiB

Open AccessArticle

The Signal Peptide and Chaperone UNC93B1 Both Influence TLR8 Ectodomain Intracellular Endosomal Localization

by Da Ao, Xueliang Liu, Sen Jiang, Yulin Xu, Wanglong Zheng, Nanhua Chen, François Meurens and Jianzhong Zhu

Vaccines 2022, 10(1), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10010014 - 23 Dec 2021

Viewed by 2585

Abstract

Toll-like receptor 8 (TLR8) is a single-stranded RNA sensing receptor and is localized in the cellular compartments, where it encounters foreign or self-nucleic acids and activates innate and adaptive immune responses. However, the mechanism controlling intracellular localization TLR8 is not completely resolved. We [...] Read more.

Toll-like receptor 8 (TLR8) is a single-stranded RNA sensing receptor and is localized in the cellular compartments, where it encounters foreign or self-nucleic acids and activates innate and adaptive immune responses. However, the mechanism controlling intracellular localization TLR8 is not completely resolved. We previously revealed the intracellular localization of TLR8 ectodomain (ECD), and in this study, we investigated the mechanism of the intracellular localization. Here we found that TLR8 ECDs from different species as well as ECDs from different TLRs are all intracellularly localized, similarly to the full-length porcine TLR8. Furthermore, porcine, bovine, and human TLR8 ECDs are all localized in cell endosomes, reflecting the cellular localization of TLR8. Intriguingly, none of post-translational modifications at single sites, including glycosylation, phosphorylation, ubiquitination, acetylation, and palmitoylation alter porcine TLR8-ECD endosomal localization. Nevertheless, the signal peptide of porcine TLR8-ECD determines its endosomal localization. On the other hand, signaling regulator UNC93B1 also decides the endosomal localization of porcine, bovine, and human TLR8 ECDs. The results from this study shed light on the mechanisms of not only TLR8 intracellular localization but also the TLR immune signaling. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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12 pages, 1666 KiB

Open AccessArticle

Passive Immunisation against RHDV2 Induces Protection against Disease but Not Infection

by Robyn N. Hall, Tegan King, Tiffany W. O’Connor, Andrew J. Read, Sylvia Vrankovic, Melissa Piper and Tanja Strive

Vaccines 2021, 9(10), 1197; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9101197 - 18 Oct 2021

Cited by 7 | Viewed by 1865

Abstract

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to [...] Read more.

Rabbit haemorrhagic disease virus 2 (RHDV2) is a lagovirus in the family Caliciviridae. The closely related Rabbit haemorrhagic disease virus (RHDV, termed RHDV1 throughout this manuscript for clarity) has been used extensively as a biocontrol agent in Australia since the mid-1990s to manage wild rabbit populations, a major economic and environmental pest species. Releasing RHDV1 into populations with a high proportion of rabbits less than 8–10 weeks of age leads to non-lethal infection in many of these young animals, with subsequent seroconversion and long-term immunity against reinfection. In contrast, RHDV2 causes lethal disease even in young rabbits, potentially offering substantial benefits for rabbit management programs over RHDV1. However, it is not clear how acquired resistance from maternal antibodies may influence immunity after RHDV2 infection. In this study, we assessed serological responses after RHDV2 challenge in young rabbits of three different ages (5-, 7-, or 9-weeks-old) that were passively immunised with either high- (titre of 2560 by RHDV IgG ELISA; 2.41 mg/mL total protein) or low- (titre of 160–640 by RHDV IgG ELISA; 1.41 mg/mL total protein) dose RHDV2 IgG to simulate maternal antibodies. All rabbits treated with a high dose and 75% of those treated with a low dose of RHDV2 IgG survived virus challenge. Surviving animals developed robust lagovirus-specific IgA, IgM, and IgG responses within 10 days post infection. These findings demonstrate that the protection against RHDV2 conferred by passive immunisation is not sterilising. Correspondingly, this suggests that the presence of maternal antibodies in wild rabbit populations may impede the effectiveness of RHDV2 as a biocontrol. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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Review

Jump to: Research, Other

12 pages, 1986 KiB

Open AccessReview

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

by John Joseph

Vaccines 2022, 10(11), 1932; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10111932 - 15 Nov 2022

Cited by 2 | Viewed by 3732

Abstract

Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against emerging viral variants. Growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate [...] Read more.

Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against emerging viral variants. Growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. The review further elaborates on the potential of trained immunity to leverage protection against pathogens via the molecular patterns of antigens by pathogen recognition receptors (PPRs) on innate immune cells. The review also focuses on integrating trained innate memory with adaptive memory to shape next-generation vaccines by coupling each one’s unique characteristics. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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27 pages, 1194 KiB

Open AccessReview

COVID-19-Associated Mucormycosis: A Matter of Concern Amid the SARS-CoV-2 Pandemic

by Pankaj Chandley, Priyanka Subba and Soma Rohatgi

Vaccines 2022, 10(8), 1266; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10081266 - 06 Aug 2022

Cited by 10 | Viewed by 4717

Abstract

Mucormycosis is an invasive fungal infection caused by fungi belonging to order Mucorales. Recently, with the increase in COVID-19 infections, mucormycosis infections have become a matter of concern globally, because of the high morbidity and mortality rates associated with them. Due to the [...] Read more.

Mucormycosis is an invasive fungal infection caused by fungi belonging to order Mucorales. Recently, with the increase in COVID-19 infections, mucormycosis infections have become a matter of concern globally, because of the high morbidity and mortality rates associated with them. Due to the association of mucormycosis with COVID-19 disease, it has been termed COVID-19-associated mucormycosis (CAM). In the present review, we focus on mucormycosis incidence, pathophysiology, risk factors, immune dysfunction, interactions of Mucorales with endothelial cells, and the possible role of iron in Mucorales growth. We review the limitations associated with current diagnostic procedures and the requirement for more specific, cost-effective, convenient, and sensitive assays, such as PCR-based assays and monoclonal antibody-based assays for the effective diagnosis of mucormycosis. We discuss the current treatment options involving antifungal drug therapies, adjunctive therapy, surgical treatment, and their limitations. We also review the importance of nutraceuticals-based therapy for the prevention as well as treatment of mucormycosis. Our review also highlights the need to explore the potential of novel immunotherapeutics, which include antibody-based therapy, cytokine-based therapy, and combination/synergistic antifungal therapy, as treatment options for mucormycosis. In summary, this review provides a complete overview of COVID-19-associated mucormycosis, addressing the current research gaps and future developments required in the field. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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Other

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9 pages, 939 KiB

Open AccessBrief Report

Prolonged Protective Immunity Induced by Mild SARS-CoV-2 Infection of K18-hACE2 Mice

by Liat Bar-On, Moshe Aftalion, Efi Makdasi, David Gur, Ron Alcalay, Hila Cohen, Adi Beth-Din, Ronit Rosenfeld, Hagit Achdout, Erez Bar-Haim, Reut Falach, Theodor Chitlaru and Ofer Cohen

Vaccines 2022, 10(4), 613; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10040613 - 14 Apr 2022

Cited by 3 | Viewed by 1467

Abstract

Longevity of the immune response following viral exposure is an essential aspect of SARS-CoV-2 infection. Mild SARS-CoV-2 infection of K18-hACE2 mice was implemented for evaluating the mounting and longevity of a specific memory immune response. We show that the infection of K18-hACE2 mice [...] Read more.

Longevity of the immune response following viral exposure is an essential aspect of SARS-CoV-2 infection. Mild SARS-CoV-2 infection of K18-hACE2 mice was implemented for evaluating the mounting and longevity of a specific memory immune response. We show that the infection of K18-hACE2 mice induced robust humoral and cellular immunity (systemic and local), which persisted for at least six months. Virus-specific T cells and neutralizing antibody titers decreased over time, yet their levels were sufficient to provide sterile immunity against lethal rechallenge six months post-primary infection. The study substantiates the role of naturally induced immunity against SARS-CoV-2 infection for preventing recurring morbidity. Full article

(This article belongs to the Special Issue Feature Papers of Pathogens-Host Immune Interface)

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