scholarly journals Predicting the risk of re-infection from SARS-CoV-2 using the known pattern of adaptive immune response to previous human coronavirus outbreaks

2020 ◽  
Author(s):  
Ademola Samuel Ojo ◽  
Paul Toluwatope Okediji ◽  
Ayotemide P. Akin-Onitolo ◽  
Olusegun S. Ojo ◽  
Oluyinka Oladele Opaleye
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
The Body ◽  
Short Term ◽  
Adaptive Immune ◽  
Short And Long Term

This paper attempts to answer the question: are recovered COVID-19 patients protected from re-infection? This review draws evidence from comparisons between immune responses to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV), which are phylogenetically closely related to Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). Relevant studies were identified and reviewed based on searches conducted using PubMed. Full-text original studies on short- and long-term immune responses to human coronaviruses were included. The immune dysfunction and clinical manifestations in SARS-CoV-2, SARS-CoV, and MERS-CoV were found to be similar. Infections with SARS-CoV and MERS-CoV trigger the production of antibodies and memory B- and T-cells. Serum IgM is detectable within 7 days, peak at 21-30 days and become undetectable by 180 days. IgG is detectable at 7 days, peak at 90 days, and decline to undetected levels by 2 years post-infection. Memory B- and T-cells persist in the body for up to 2 and 6 years respectively after initial infection. The short-term risk of SARS-CoV-2 re-infection is predictably low based on similarities in the short term adaptive immune response to kindred coronaviruses. However, more research will be required to determine the long-term adaptive immunity to SARS-CoV-2 and factors that may influence the existence of short- and long-term immunity against the virus.

scholarly journals mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2

2020 ◽  
Author(s):  
Mariah Hassert ◽  
Elizabeth Geerling ◽  
E. Taylor Stone ◽  
Tara L. Steffen ◽  
Madi S. Feldman ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Expression System ◽  
Adaptive Immune Response ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Adaptive Immune

AbstractThe novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.

scholarly journals Overexpression of Interleukin-15 Compromises CD4-Dependent Adaptive Immune Responses against Herpes Simplex Virus 2

2008 ◽  
Vol 83 (2) ◽  
pp. 918-926 ◽  
Author(s):  
Navkiran Gill ◽  
Ali A. Ashkar
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Interleukin 15 ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACT Interleukin-15 (IL-15) is necessary for the development and function of NK/NKT cells and the maintenance of naive and memory CD8+ T cells. In the absence of IL-15, protective innate immunity is not available; however, a functional adaptive immune response against vaginal herpes simplex virus 2 (HSV-2) is generated. Mice overexpressing IL-15 (IL-15tg mice) have higher numbers of NK cells, greater NK-derived gamma interferon, and more CD8+ T cells. Here we examined the consequences of IL-15 overexpression for innate and adaptive immunity against genital HSV-2. Surprisingly, IL-15tg mice immunized against HSV-2 were not protected against genital HSV-2 challenge compared to control immunized mice. IL-15tg mice had a higher frequency of NK cells in the genital mucosa than control mice. However, immunized IL-15tg mice had significantly lower numbers of HSV-2-specific CD4+ T cells than B6 mice. We then confirmed that CD4+ T cells, but not CD8+ T cells, are essential for protection against intravaginal HSV-2 challenge. Since we observed less protection in immunized IL-15tg mice, we then examined if the adaptive immune responses generated in an environment with overexpression of IL-15 could provide protection against HSV-2 in an environment with normal levels of IL-15 expression. We adoptively transferred immunized cells from IL-15tg and B6 mice into naive RAG-1−/− mice and found that the cells from immunized IL-15tg mice were able to provide protection in this IL-15-normal environment. Our data suggest that overexpression of IL-15 results in a reduced CD4+ T cell-mediated adaptive immune response against genital HSV-2.

scholarly journals mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2

2020 ◽  
Vol 16 (12) ◽  
pp. e1009163
Author(s):  
Mariah Hassert ◽  
Elizabeth Geerling ◽  
E. Taylor Stone ◽  
Tara L. Steffen ◽  
Madi S. Feldman ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Adaptive Immune Response ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Peptide Epitopes ◽  
Adaptive Immune

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Critical to the rapid evaluation of vaccines and antivirals against SARS-CoV-2 is the development of tractable animal models to understand the adaptive immune response to the virus. To this end, the use of common laboratory strains of mice is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Importantly, using this system, we functionally identified the CD4+ and CD8+ structural peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice and confirmed their existence in an established model of SARS-CoV-2 pathogenesis. We demonstrated that, identical to what has been seen in humans, the antigen-specific CD8+ T cells in mice primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. As the focus of the immune response in mice is highly similar to that of the humans, the identification of functional murine SARS-CoV-2-specific T cell epitopes provided in this study will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2 infection.

scholarly journals Long-term expansion of effector/memory Vδ2− γδ T cells is a specific blood signature of CMV infection

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1317-1324 ◽  
Author(s):  
Vincent Pitard ◽  
David Roumanes ◽  
Xavier Lafarge ◽  
Lionel Couzi ◽  
Isabelle Garrigue ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Adaptive Immune Response ◽  
Γδ T Cells ◽  
Effector Memory ◽  
Γδ T Cell ◽  
Cmv Infection ◽  
Adaptive Immune

Abstract The ability of human γδ T cells to develop immunologic memory is still a matter of debate. We previously demonstrated the involvement of Vδ2− γδ T lymphocytes in the response of immunosuppressed organ recipients to cytomegalovirus (CMV). Here, we demonstrate their ability to mount an adaptive immune response to CMV in immunocompetent subjects. Vδ2− γδ T-cell peripheral blood numbers, repertoire restriction, and cytotoxicity against CMV-infected fibroblasts were markedly increased in CMV-seropositive, compared with CMV-seronegative, healthy persons. Whereas Vδ2− γδ T cells were found as naive cells in CMV− patients, they virtually all exhibited the cytotoxic effector/memory phenotype in CMV+ patients, which is also observed in transplanted patients challenged with CMV. This long-term complete remodeling of the Vδ2− γδ T-cell population by CMV predicts their ability to exhibit an adaptive anti-CMV immune response. Consistent with this, we observed that the secondary response to CMV was associated with a faster γδ T-cell expansion and a better resolution of infection than the primary response. In conclusion, the increased level of effector-memory Vδ2− γδ T cells in the peripheral blood is a specific signature of an adaptive immune response to CMV infection of both immunocompetent and immunosuppressed patients.

scholarly journals Clinical outcomes of prexasertib monotherapy in recurrent BRCA wild-type high-grade serous ovarian cancer involve innate and adaptive immune responses

2020 ◽  
Vol 8 (2) ◽  
pp. e000516
Author(s):  
Erika J Lampert ◽  
Ashley Cimino-Mathews ◽  
Joo Sang Lee ◽  
Jayakumar Nair ◽  
Min-Jung Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Cell Cycle Checkpoint ◽  
High Grade ◽  
Blood Samples ◽  
Adaptive Immune ◽  
Cycle Checkpoint

BackgroundPreclinical data suggest cell cycle checkpoint blockade may induce an immunostimulatory tumor microenvironment. However, it remains elusive whether immunomodulation occurs in the clinical setting. To test this, we used blood and fresh tissue samples collected at baseline and post therapy from a phase II trial of the cell cycle checkpoint 1 inhibitor (CHK1i) prexasertib in recurrent ovarian cancer.MethodsPaired blood samples and fresh core biopsies, taken before treatment was started at baseline (cycle 1 day 1 (C1D1)) and post second dose on day 15 of cycle 1 (C1D15), were collected. To evaluate changes in the immune responses after treatment, multiparametric flow cytometry for DNA damage markers and immune cell subsets was performed on paired blood samples. RNA sequencing (RNAseq) of paired core biopsies was also analyzed. Archival tissue immune microenvironment was evaluated with immunohistochemistry. All correlative study statistical analyses used two-sided significance with a cut-off of p=0.05.ResultsFlow cytometric analysis showed significantly increased γ-H2AX staining after CHK1i treatment, accompanied by increased monocyte populations, suggestive of an activated innate immune response (median 31.6% vs 45.6%, p=0.005). Increased expressions of immunocompetence marker HLA-DR (Human Leukocyte Antigen DR antigen) on monocytes and of TBK1, a marker of STING (stimulator of interferon genes) pathway activation, in biopsies were associated with improved progression-free survival (PFS) (9.25 vs 3.5 months, p=0.019; 9 vs 3 months, p=0.003, respectively). Computational analysis of RNAseq data indicated increased infiltration of tumor niches by naïve B-cells and resting memory T-cells, suggestive of a possibly activated adaptive immune response, and greater T-reg infiltration after treatment correlated with worse PFS (9.25 vs 3.5 months, p=0.007). An immunosuppressive adaptive immune response, perhaps compensatory, was also observed on flow cytometry, including lymphodepletion of total peripheral CD4+ and CD8+T cells after CHK1i and an increase in the proportion of T-regs among these T-cells. Additionally, there was a trend of improved PFS with greater tumor-infiltrating lymphocytes (TILs) in archival tissues (13.7 months >30% TILs vs 5.5 months ≤30% TILs, p=0.05).ConclusionOur study demonstrates that a favorable clinical response in high-grade serous ovarian carcinoma patients treated with CHK1i is possibly associated with enhanced innate and adaptive immunity, requiring further mechanistic studies. It is supportive of current efforts for a clinical development strategy for therapeutic combinations with immunotherapy in ovarian cancer.

scholarly journals Primary infection by E. multilocularis induces distinct patterns of crosstalk between hepatic regulatory T and natural killer T cells in mice

2021 ◽  
Author(s):  
Tural Yarahmadov ◽  
Junhua Wang ◽  
Daniel Sanchez-Talavull ◽  
Christian A Alvarez Rojas ◽  
Tess Brodie ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Adaptive Immune Response ◽  
Natural Killer T Cells ◽  
Adaptive Immune ◽  
Hepatic Lesions ◽  
Killer T Cells ◽  
Natural Killer T

The larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Recently, opportunistic properties of the disease have been proposed based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, little is known about how the local hepatic immune responses modulate the infection with E. multilocularis. In a mouse model of oral infection that mimics the normal infection route in human patients, the adaptive immune response in the liver was assessed using single-cell RNA sequencing of isolated hepatic CD3+ T cells at different infection stages. We observed an early significant increase in regulatory T and natural killer T cells in parallel with an active downregulation of CD4+ and CD8+ T cells. Early interactions between regulatory T cells and natural killer T cells indicate a promotion of the formation of hepatic lesions and later contribute to suppression of the resolution of parasite-induced pathology. The obtained data provides a fresh insight on the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.

Double positive CD4+CD8+ T cells are part of the adaptive immune response against Candida albicans

2019 ◽  
Vol 80 (12) ◽  
pp. 999-1005 ◽  
Author(s):  
Barbara Misme-Aucouturier ◽  
Adel Touahri ◽  
Marjorie Albassier ◽  
Francine Jotereau ◽  
Patrice Le Pape ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Candida Albicans ◽  
Cd8 T Cells ◽  
Adaptive Immune Response ◽  
Double Positive ◽  
Adaptive Immune

scholarly journals Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoping Ma ◽  
Jing Hu ◽  
Yan Yu ◽  
Chengdong Wang ◽  
Yu Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Pulmonary Hemorrhage ◽  
Cladosporium Cladosporioides ◽  
Th2 Cells ◽  
Intercellular Adhesion Molecule ◽  
Post Inoculation ◽  
Adaptive Immune ◽  
Systemic Infections

AbstractCladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.

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