scholarly journals Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Matrix Protein ◽  
Cell Epitope ◽  
Vaccine Antigen ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
C Terminus ◽  
The Impact ◽  
Stimulation Of

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

scholarly journals Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity

2020 ◽  
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Cell Epitope ◽  
Vaccine Antigen ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
C Terminus ◽  
The Difference ◽  
The Impact ◽  
Stimulation Of

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shape nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a non-coding ssRNA template. The PapMV nanoparticle induces innate immunity through stimulation of the toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, either at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the CTL epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C) using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate the TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals Reply to “Nuclear Export Signal and Immunodominant CD8+T Cell Epitope in Influenza A Virus Matrix Protein 1”

2012 ◽  
Vol 86 (18) ◽  
pp. 10259-10260
Author(s):  
Shuai Cao ◽  
Yi Shi ◽  
Shuguang Tan ◽  
Hao Song ◽  
George F. Gao ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Nuclear Export ◽  
Influenza A ◽  
Matrix Protein ◽  
Nuclear Export Signal ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Export Signal

Targeted Depletion and Inhibition of Activated T Lymphocytes with SGN-70, a Humanized Antibody Specific for the Activation Antigen CD70.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1728-1728
Author(s):  
Julie A. McEarchern ◽  
Kerry Klussman ◽  
Tamar E. Boursalian ◽  
Iqbal S. Grewal ◽  
Che-Leung Law
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Influenza A ◽  
Matrix Protein ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Cell Subset ◽  
Activated T Cells ◽  
Stimulation Of

Abstract CD70 (CD27L) is a member of the tumor necrosis factor superfamily that is predominantly expressed on activated lymphocytes and is important for generation of B and T memory and effector responses. High levels of CD70 are also found on chronically activated T cells and lymphocytes in patients with autoimmune disorders. Blockade of CD70 interaction with its receptor has been shown to inhibit the onset of experimental autoimmune encephalomyelitis and cardiac allograft rejection in mice. We have engineered a humanized anti-CD70, SGN-70, that mediates Fc-dependent antibody effector functions and blocks binding of CD70 to its receptor. In this report we show that SGN-70 inhibits co-stimulation of T lymphocytes, and selectively depletes CD70+ activated T cells. Depletion of antigen-specific T cells by SGN-70 was demonstrated using CD8+ T cells specific for a peptide (M58-66) derived from the influenza A matrix protein M1. Stimulation of peripheral blood mononuclear cells with the M1 peptide markedly induced CD70 expression within a discrete expanding of M1 peptide-specific CD8+Vβ17+ T cell subset. Treatment of peptide-stimulated cultures with SGN-70 (0.01–1 μg/mL) decreased the number of CD70+CD8+Vβ17+ cells by >80%. This depletion was dependent on the activity of CD16+ cells within the culture since blocking CD16 completely eliminated the depleting effect of SGN-70. Non-activated Vβ17 negative cells were not affected by SGN-70 and were functionally equivalent to untreated control cultures in subsequent response to mitogenic re-stimulation. Together, these data demonstrate the capacity of SGN-70 to selectively target activated cells and its potential to limit expansion of antigen-specific T lymphocytes. Thus, SGN-70 may have therapeutic potential to target T cell-mediated autoimmune and inflammatory diseases.

scholarly journals The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0122282 ◽  
Author(s):  
Iana H. Haralambieva ◽  
Scott D. Painter ◽  
Richard B. Kennedy ◽  
Inna G. Ovsyannikova ◽  
Nathaniel D. Lambert ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Influenza A ◽  
Humoral Immune ◽  
Influenza A H1n1 ◽  
Older Subjects ◽  
Response Variation ◽  
The Impact

Manipulating the immune system for pigs to optimise performance

2018 ◽  
Vol 58 (4) ◽  
pp. 666 ◽  
Author(s):  
J. R. Pluske ◽  
J. C. Kim ◽  
J. L. Black
Keyword(s):  
Amino Acids ◽  
Immune Response ◽  
Immune System ◽  
Prostaglandin E2 ◽  
Acute Phase Proteins ◽  
Production Cycle ◽  
Pig Performance ◽  
The Impact ◽  
Pig Health ◽  
Stimulation Of

Disease and enhanced microbial load are considered to be major factors limiting the performance and overall efficiency of feed use by pigs in Australian piggeries. It is recognised that pigs exposed to conventional housing systems with high microbial loads grow 10–20% more slowly than do gnotobiotic pigs or pigs kept in ‘clean’ environments. Consequently, a proportion of pigs in any production cycle are continuously being challenged by their immediate environment, which can cause an immune response to be mounted. Such a process is physiologically expensive in terms of energy and protein (comprised of amino acids), with, for example, the enhanced rate of protein turnover associated with the production of immune cells, antibodies and acute-phase proteins increasing energy expenditure by 10–15% of maintenance needs and protein requirements by 7–10%. The requirements for lysine, tryptophan, sulfur-containing amino acids and threonine can be increased by a further 10%. The over-stimulation of the immune response with excess production of pro-inflammatory cytokines causes excessive production primarily of the prostaglandin E2 (PGE2), which contributes to anorexia, fever and increased proteolysis, and a concomitant reduction in pig performance. Prostaglandin E2 is produced from dietary and cell-membrane phospholipids via secretory phospholipase A2 (sPLA2) to produce arachidonic acid, which is catalysed by the COX-2 enzyme. Negating the negative effects of PGE2 appears not to adversely affect the ability of the immune system to combat pathogens, but improves pig performance. There are negative outcomes for pig health and productivity through both under- and over-stimulation of the immune response. This review briefly outlines the impact of immune stimulation on pigs and discusses strategies to optimise the immune response for pig health and performance.

scholarly journals Increased Immunogenicity of Full-Length Protein Antigens through Sortase-Mediated Coupling on the PapMV Vaccine Platform

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 49 ◽  
Author(s):  
Marie-Ève Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Ariane Thérien ◽  
Caroline Garneau ◽  
Philippe Casault ◽  
...  
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Specific Protein ◽  
Full Length ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
Viral Antigens ◽  
Covalently Linked ◽  
Papmv Nanoparticles

Background: Flexuous rod-shape nanoparticles—made of the coat protein of papaya mosaic virus (PapMV)—provide a promising vaccine platform for the presentation of viral antigens to immune cells. The PapMV nanoparticles can be combined with viral antigens or covalently linked to them. The coupling to PapMV was shown to improve the immune response triggered against peptide antigens (<39 amino acids) but it remains to be tested if large proteins can be coupled to this platform and if the coupling will lead to an immune response improvement. Methods: Two full-length recombinant viral proteins, the influenza nucleoprotein (NP) and the simian immunodeficiency virus group-specific protein antigen (GAG) were coupled to PapMV nanoparticles using sortase A. Mice were immunized with the nanoparticles coupled to the antigens and the immune response directed to the antigens were analyzed by ELISA and ELISPOT. Results: We showed the feasibility of coupling two different full-length proteins (GAG and NP) to the nanoparticle. We also showed that the coupling to PapMV nanoparticles improved significantly the humoral and the cytotoxic T lymphocyte (CTL) immune response to the antigens. Conclusion: This proof of concept demonstrates the versatility and the efficacy of the PapMV vaccine platform in the design of vaccines against viral diseases.

scholarly journals Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 40

2020 ◽  
Vol 101 (8) ◽  
pp. 853-862
Author(s):  
Kikue Saika ◽  
Masahiko Kato ◽  
Hideaki Sanada ◽  
Sho Matsushita ◽  
Masanori Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Matrix Protein ◽  
Insect Cells ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Vaccine Platform ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Ctl Epitope

Simian virus 40 (SV40) is a monkey polyomavirus. The capsid structure is icosahedral and comprises VP1 units that measure 45 nm in diameter. Five SV40 VP1 molecules form one pentamer subunit, and a single icosahedral subunit comprises 72 pentamers; a single SV40 VP1 capsid comprises 360 SV40 VP1 molecules. In a previous study, we showed that an influenza A virus matrix protein 1 (M1) CTL epitope inserted within SV40 virus-like particles (VLPs) induced cytotoxic T lymphocytes (CTLs) without the need for an adjuvant. Here, to address whether SV40 VLPs induce adaptive immune responses against VLP-incorporated antigens, we prepared SV40 VLPs containing M1 or chicken ovalbumin (OVA). This was done by fusing M1 or OVA with the carboxyl terminus of SV40 VP2 and co-expressing them with SV40 VP1 in insect cells using a baculovirus vector. Intraperitoneal (i.p.) or intranasal administration of SV40 VLPs incorporating M1 induced the production of CTLs specific for the M1 epitope without the requirement for adjuvant. The production of antibodies against SV40 VLPs was also induced by i.p. administration of SV40 VLPs in the absence of adjuvant. Finally, the administration of SV40 VLPs incorporating OVA induced anti-OVA antibodies in the absence of adjuvant; in addition, the level of antibody production was comparable with that after i.p. administration of OVA plus alum adjuvant. These results suggest that the SV40 capsid incorporating foreign antigens can be used as a vaccine platform to induce adaptive immune responses without the need for adjuvant.

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