scholarly journals Recombinant single-cycle influenza virus as a new tool to augment antitumour immunity with immune checkpoint inhibitors

2021 ◽  
Author(s):  
Matheswaran Kandasamy

Virus-based tumour vaccines offer many advantages compared to other antigen delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (S-NY-ESO-1 FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1 specific CD8+T cell response in lungs and spleen that resulted in the regression of NY-ESO-1 expressing lung tumour and subcutaneous tumour respectively. Combined administration with anti PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen specific CD8+T cell response and protection against tumour development in combination with PD-1 blockade.

2003 ◽  
Vol 198 (3) ◽  
pp. 399-410 ◽  
Author(s):  
Sherry R. Crowe ◽  
Stephen J. Turner ◽  
Shannon C. Miller ◽  
Alan D. Roberts ◽  
Rachel A. Rappolo ◽  
...  

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.


Nano Letters ◽  
2014 ◽  
Vol 14 (9) ◽  
pp. 5458-5470 ◽  
Author(s):  
Paula Cristina Batista de Faria ◽  
Luara Isabela dos Santos ◽  
João Paulo Coelho ◽  
Henrique Bücker Ribeiro ◽  
Marcos Assunção Pimenta ◽  
...  

2013 ◽  
Vol 87 (23) ◽  
pp. 12510-12522 ◽  
Author(s):  
Nayana Prabhu ◽  
Adrian W. Ho ◽  
Kenneth H. S. Wong ◽  
Paul Edward Hutchinson ◽  
Yen Leong Chua ◽  
...  

The factors that regulate the contraction of the CD8 T cell response and the magnitude of the memory cell population against localized mucosal infections such as influenza are important for generation of efficient vaccines but are currently undefined. In this study, we used a mouse model of influenza to demonstrate that the absence of gamma interferon (IFN-γ) or IFN-γ receptor 1 (IFN-γR1) leads to aberrant contraction of antigen-specific CD8 T cell responses. The increased accumulation of the effector CD8 T cell population was independent of viral load. Reduced contraction was associated with an increased fraction of CD8 T cells expressing the interleukin-7 receptor (IL-7R) at the peak of the response, resulting in enhanced numbers of memory/memory precursor cells in IFN-γ−/−and IFN-γR−/−compared to wild-type (WT) mice. Blockade of IL-7 within the lungs of IFN-γ−/−mice restored the contraction of influenza virus-specific CD8 T cells, indicating that IL-7R is important for survival and is not simply a consequence of the lack of IFN-γ signaling. Finally, enhanced CD8 T cell recall responses and accelerated viral clearance were observed in the IFN-γ−/−and IFN-γR−/−mice after rechallenge with a heterologous strain of influenza virus, confirming that higher frequencies of memory precursors are formed in the absence of IFN-γ signaling. In summary, we have identified IFN-γ as an important regulator of localized viral immunity that promotes the contraction of antigen-specific CD8 T cells and inhibits memory precursor formation, thereby limiting the size of the memory cell population after an influenza virus infection.


Author(s):  
Tania H. Watts ◽  
Gloria H.Y. Lin ◽  
Chao Wang ◽  
Ann J. McPherson ◽  
Laura M. Snell ◽  
...  

2000 ◽  
Vol 204 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Chiu-Chen Huang ◽  
Michael A. Coppola ◽  
Phuong Nguyen ◽  
Damian Carragher ◽  
Carole Rohl ◽  
...  

2003 ◽  
Vol 100 (12) ◽  
pp. 7235-7240 ◽  
Author(s):  
R. J. Webby ◽  
S. Andreansky ◽  
J. Stambas ◽  
J. E. Rehg ◽  
R. G. Webster ◽  
...  

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