scholarly journals Generation of Adaptive Immune Responses Following Influenza Virus Challenge is Not Compromised by Pre-Treatment with the TLR-2 Agonist Pam2Cys

2015 ◽  
Vol 6 ◽  
Author(s):  
Edin Jessica Mifsud ◽  
Amabel C. L. Tan ◽  
Lorena Elizabeth Brown ◽  
Brendon Yew Loong Chua ◽  
David C. Jackson
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Virus Challenge ◽  
Adaptive Immune ◽  
Pre Treatment

scholarly journals Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

Viruses ◽  
2009 ◽  
Vol 1 (3) ◽  
pp. 1022-1034 ◽  
Author(s):  
Artur Summerfield ◽  
Kenneth McCullough
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice

2020 ◽  
Author(s):  
Minami Nagai ◽  
Miyu Moriyama ◽  
Takeshi Ichinohe
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Critical Role ◽  
Influenza Virus Infection ◽  
Oral Bacteria ◽  
Antibody Responses ◽  
Adaptive Immune Responses ◽  
Adjuvant Activity ◽  
Adaptive Immune

AbstractGut microbiota plays a critical role in the induction of adaptive immune responses to influenza virus infection. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here we demonstrate that while intranasal administration of influenza virus hemagglutinin vaccine alone was insufficient to induce the vaccine-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered the split-virus vaccine. Myd88-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.

scholarly journals Influenza Virus Hemagglutinin Glycoproteins with Different N-Glycan Patterns Activate Dendritic CellsIn Vitro

2016 ◽  
Vol 90 (13) ◽  
pp. 6085-6096 ◽  
Author(s):  
Wen-Chun Liu ◽  
Yu-Li Lin ◽  
Maureen Spearman ◽  
Pei-Yun Cheng ◽  
Michael Butler ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Viral Escape ◽  
Complex Type ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Influenza Virus Hemagglutinin ◽  
High Mannose

ABSTRACTInfluenza virus hemagglutinin (HA) N-glycans play important regulatory roles in the control of virus virulence, antigenicity, receptor-binding specificity, and viral escape from the immune response. Considered essential for controlling innate and adaptive immune responses against influenza virus infections, dendritic cells (DCs) trigger proinflammatory and adaptive immune responses in hosts. In this study, we engineered Chinese hamster ovary (CHO) cell lines expressing recombinant HA from pandemic H1, H5, and H7 influenza viruses. rH1HA, rH5HA, and rH7HA were obtained as wild-type proteins or in the presence of kifunensine (KIF) or further with endo-β-N-acetylglucosaminidase-treated KIF (KIF+E) to generate single-N-acetylglucosamine (GlcNAc) N-glycans consisting of (i) terminally sialylated complex-type N-glycans, (ii) high-mannose-type N-glycans, and (iii) single-GlcNAc-type N-glycans. Our results show that high-mannose-type and single-GlcNAc-type N-glycans, but not complex-type N-glycans, are capable of inducing more active hIL12 p40, hIL12 p70, and hIL-10 production in human DCs. Significantly higher HLA-DR, CD40, CD83, and CD86 expression levels, as well reduced endocytotic capacity in human DCs, were noted in the high-mannose-type rH1HA and single-GlcNAc-type rH1HA groups than in the complex-type N-glycan rH1HA group. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). The high-mannose-type or single-GlcNAc-type N-glycans of both avian and human HA types are more stimulatory than the complex-type N-glycans. HA-stimulated DC activation was accomplished partially through a mannose receptor(s). These results provide more understanding of the contribution of glycosylation of viral proteins to the immune responses and may have implications for vaccine development.IMPORTANCEInfluenza viruses trigger seasonal epidemics or pandemics with mild-to-severe consequences for human and poultry populations. DCs are the most potent professional antigen-presenting cells, which play a crucial role in the link between innate and adaptive immunity. In this study, we obtained stable-expression CHO cells to produce rH1HA, rH5HA, and rH7HA proteins containing distinct N-glycan patterns. These rHA proteins, each with a distinct N-glycan pattern, were used to investigate interactions with mouse and human DCs. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). High-mannose-type and single-GlcNAc-type N-glycans were more effective than complex-type N-glycans in triggering mouse and human DC activation and maturation. We believe these results provide some useful information for influenza vaccine development regarding how influenza virus HA proteins with different types of N-glycans activate DCs.

scholarly journals Virus-Like Particles Are a Superior Platform for Presenting M2e Epitopes to Prime Humoral and Cellular Immunity against Influenza Virus

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 66 ◽  
Author(s):  
Ki-Hye Kim ◽  
Young-Man Kwon ◽  
Young-Tae Lee ◽  
Min-Chul Kim ◽  
Hye Hwang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Cross Protection ◽  
Effective Vaccine ◽  
Vaccine Platform ◽  
Adaptive Immune Responses ◽  
Virus Like Particles ◽  
Adaptive Immune ◽  
Antigenic Properties

Influenza virus M2 protein has a highly conserved ectodomain (M2e) as a cross-protective antigenic target. We investigated the antigenic and immunogenic properties of tandem repeat M2e (5xM2e) proteins and virus-like particles (5xM2e VLP) to better understand how VLP and protein platform vaccines induce innate and protective adaptive immune responses. Despite the high antigenic properties of 5xM2e proteins, the 5xM2e VLP was superior to 5xM2e proteins in inducing IgG2a isotype antibodies, T cell responses, plasma cells and germinal center B cells as well as in conferring cross protection. Mice primed with 5xM2e VLP were found to be highly responsive to 5xM2e protein boost, overcoming the low immunogenicity and protective efficacy of 5xM2e proteins. Immunogenic differences between VLPs and proteins in priming immune responses might be due to an intrinsic ability of 5xM2e VLP to stimulate dendritic cells secreting T helper type 1 (Th1) cytokines. We also found that 5xM2e VLP was effective in inducing inflammatory cytokines and chemokines, and in recruiting macrophages, monocytes, neutrophils, and CD11b+ dendritic cells at the injection site. Therefore, this study provides evidence that 5xM2e VLP is an effective vaccine platform, inducing cross-protection by stimulating innate and adaptive immune responses.

scholarly journals Benefits and Perils of Necroptosis in Influenza Virus Infection

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Siddharth Balachandran ◽  
Glenn F. Rall
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Cell Types ◽  
Influenza A Viruses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Infected Cells

ABSTRACT Influenza A viruses (IAV) are lytic viruses that have recently been found to activate necroptosis in many of the cell types they infect. Necroptotic cell death is potently immunogenic and limits IAV spread by directly eliminating infected cells and by mobilizing both innate and adaptive immune responses. The benefits of necroptosis to the host, however, may sometimes be outweighed by the potentially deleterious hyperinflammatory consequences of activating this death modality in pulmonary and other tissues.

scholarly journals Disruption of Nasal Bacteria Enhances Protective Immune Responses to Influenza A Virus and SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Minami Nagai ◽  
Miyu Moriyama ◽  
Takeshi Ichinohe
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Specific Antibody ◽  
Critical Role ◽  
Influenza Virus Infection ◽  
Oral Bacteria ◽  
Antibody Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Abstract Background: Gut microbiota and these microbial-derived products play a critical role in the induction of adaptive immune responses to influenza virus infection. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here, we examine whether nasal bacteria critically regulates the generation of influenza virus specific adaptive immune response after infection or intranasal vaccination. Results: We demonstrated that disruption of nasal bacteria by topical mucosal application of antibiotic enhances the virus-specific antibody responses to influenza virus infection. Although intranasal administration of hemagglutinin (HA) vaccine alone was insufficient to induce the HA-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered split-virus vaccines. Myd88-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection.Conclusion: We show for the first time that disruption of nasal bacteria enhances protective immune responses to influenza virus and SARS-CoV-2 infection. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.

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