Immune Escape
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2022 ◽  
Vol 104 ◽  
pp. 108512
Author(s):  
Yue Ding ◽  
Yilin Yan ◽  
Yihui Dong ◽  
Jingyuan Xu ◽  
Wei Su ◽  
...  

Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 99
Author(s):  
Stephane Delbecq

Human babesiosis results from a combination of tick tropism for humans, susceptibility of a host to sustain Babesia development, and contact with infected ticks. Climate modifications and increasing diagnostics have led to an expanded number of Babesia species responsible for human babesiosis, although, to date, most cases have been attributed to B. microti and B. divergens. These two species have been extensively studied, and in this review, we mostly focus on the antigens involved in host–parasite interactions. We present features of the major antigens, so-called Bd37 in B. divergens and BmSA1/GPI12 in B. microti, and highlight the roles of these antigens in both host cell invasion and immune response. A comparison of these antigens with the major antigens found in some other Apicomplexa species emphasizes the importance of glycosylphosphatidylinositol-anchored proteins in host–parasite relationships. GPI-anchor cleavage, which is a property of such antigens, leads to soluble and membrane-bound forms of these proteins, with potentially differential recognition by the host immune system. This mechanism is discussed as the structural basis for the protein-embedded immune escape mechanism. In conclusion, the potential consequences of such a mechanism on the management of both human and animal babesiosis is examined.


2022 ◽  
Vol 12 ◽  
Author(s):  
Hui Zhang ◽  
Shuang Cao ◽  
Yang Gao ◽  
Xiao Sun ◽  
Fanming Jiang ◽  
...  

A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.


2022 ◽  
Author(s):  
Hannah Hussey ◽  
Mary-Ann Davies ◽  
Alexa Heekes ◽  
Carolyn Williamson ◽  
Ziyaad Valley-Omar ◽  
...  

Background Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the transition period was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results 150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.


2022 ◽  
Vol 18 (1) ◽  
pp. e1010200
Author(s):  
Aparna Jorapur ◽  
Lisa A. Marshall ◽  
Scott Jacobson ◽  
Mengshu Xu ◽  
Sachie Marubayashi ◽  
...  

The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV+ tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed in vivo tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors.


2022 ◽  
Vol 18 (1) ◽  
pp. e1010161
Author(s):  
César Muñoz-Fontela ◽  
Lina Widerspick ◽  
Randy A. Albrecht ◽  
Martin Beer ◽  
Miles W. Carroll ◽  
...  

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.


2022 ◽  
Author(s):  
Cameron A Smith ◽  
Ben Ashby

The apparent lack of antigenic evolution by the Delta variant (B.1.617.2) of SARS-CoV-2 during the COVID-19 pandemic is puzzling. The combination of increasing immune pressure due to the rollout of vaccines and a relatively high number of infections following the relaxation of non-pharmaceutical interventions should have created perfect conditions for immune escape variants to evolve from the Delta lineage. Instead, the Omicron variant (B.1.1.529), which is hypothesised to have evolved in an immunocompromised individual, is the first major variant to exhibit significant immune escape following vaccination programmes and is set to become globally dominant in 2022. Here, we use a simple mathematical model to explore possible reasons why the Delta lineage did not exhibit antigenic evolution and to understand how and when immunocompromised individuals affect the emergence of immune escape variants. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur, immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level, then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.


2022 ◽  
Vol 11 ◽  
Author(s):  
Jayesh Kumar Tiwari ◽  
Shloka Negi ◽  
Manju Kashyap ◽  
Sheikh Nizamuddin ◽  
Amar Singh ◽  
...  

Epithelial–mesenchymal transition (EMT) is a highly dynamic process that occurs under normal circumstances; however, EMT is also known to play a central role in tumor progression and metastasis. Furthermore, role of tumor immune microenvironment (TIME) in shaping anticancer immunity and inducing the EMT is also well recognized. Understanding the key features of EMT is critical for the development of effective therapeutic interventions. Given the central role of EMT in immune escape and cancer progression and treatment, we have carried out a pan-cancer TIME analysis of The Cancer Genome Atlas (TCGA) dataset in context to EMT. We have analyzed infiltration of various immune cells, expression of multiple checkpoint molecules and cytokines, and inflammatory and immune exhaustion gene signatures in 22 cancer types from TCGA dataset. A total of 16 cancer types showed a significantly increased (p < 0.001) infiltration of macrophages in EMT-high tumors (mesenchymal samples). Furthermore, out of the 17 checkpoint molecules we analyzed, 11 showed a significant overexpression (p < 0.001) in EMT-high samples of at least 10 cancer types. Analysis of cytokines showed significant enrichment of immunosuppressive cytokines—TGFB1 and IL10—in the EMT-high group of almost all cancer types. Analysis of various gene signatures showed enrichment of inflammation, exhausted CD8+ T cells, and activated stroma signatures in EMT-high tumors. In summary, our pan-cancer EMT analysis of TCGA dataset shows that the TIME of EMT-high tumors is highly immunosuppressive compared to the EMT-low (epithelial) tumors. The distinctive features of EMT-high tumors are as follows: (i) the enrichment of tumor-associated macrophages, (ii) overexpression of immune checkpoint molecules, (iii) upregulation of immune inhibitory cytokines TGFB1 and IL10, and (iv) enrichment of inflammatory and exhausted CD8+ T-cell signatures. Our study shows that TIMEs of different EMT groups differ significantly, and this would pave the way for future studies analyzing and targeting the TIME regulators for anticancer immunotherapy.


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