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 SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Adaptive Immune Response ◽  
Antibody Assay ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Previous Infection ◽  
A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

Adaptive immunity

2020 ◽  
pp. 325-336
Author(s):  
Paul Klenerman
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Innate Immune Response ◽  
Molecular Basis ◽  
Adaptive Immune Response ◽  
Antigenic Specificity ◽  
Adaptive Immune Responses ◽  
Research Attention ◽  
Adaptive Immune

The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.

scholarly journals Innate and Adaptive Immune Responses to Herpes Simplex Virus

Viruses ◽  
2009 ◽  
Vol 1 (3) ◽  
pp. 979-1002 ◽  
Author(s):  
Tracy Chew ◽  
Kathryne Taylor ◽  
Karen Mossman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Simplex Virus

scholarly journals Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

2008 ◽  
Vol 82 (21) ◽  
pp. 10820-10831 ◽  
Author(s):  
Subhadra Nandakumar ◽  
Stacie N. Woolard ◽  
Dorothy Yuan ◽  
Barry T. Rouse ◽  
Uday Kumaraguru
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Simplex Virus

ABSTRACT Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8+ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8+ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

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.

SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

2020 ◽  
Author(s):  
Stine SF Nielsen ◽  
Line K Vibholm ◽  
Ida Monrad ◽  
Rikke Olesen ◽  
Giacomo S Frattari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Disease Severity ◽  
Adaptive Immune Response ◽  
T Cell Responses ◽  
Adaptive Immune Responses ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Robust Adaptive

AbstractThe SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity.Author summarySARS-CoV-2 can cause severe and deadly infections. However, the immunological understanding of this viral infection is limited. Currently, several vaccines are being developed to help limit transmission and prevent the current pandemic. However, basic understanding of the adaptive immune response developed during SARS-CoV-2 infections is needed to inform further vaccine development and to understand the protective properties of the developed immune response. We investigated, the adaptive immune response developed during SARS-CoV-2 infections in recovered patients experiencing a full spectrum of disease severity, from asymptomatic infections to severe cases requiring hospitalization. We used a novel multiplex serological platform, cell-based neutralization assays and dextramer flow cytometry assays to characterize a broad and robust humoral and cellular immune response towards SARS-CoV-2. We found that the vast majority of recovered individuals have clear detectable and functional SARS-CoV-2 spike specific adaptive immune responses, despite diverse disease severities. The detection of both a humoral and cellular functional spike specific immune response in the vast majority of the individuals, irrespective of asymptomatic manifestations, supports vaccine designs currently underway, and encourages further exploration of whether primary infections provide protection to reinfection.

scholarly journals Age-Related Impairment of Innate and Adaptive Immune Responses Following Intranasal Herpes Simplex Infection

2022 ◽  
Author(s):  
Ruchi Srivastava ◽  
Anshu Agrawal ◽  
Hawa Vahed ◽  
Lbachir BenMohamed
Keyword(s):  
Immune Response ◽  
Herpes Simplex ◽  
Immune Responses ◽  
The Elderly ◽  
Adaptive Immune Responses ◽  
Herpes Infection ◽  
Aged Mice ◽  
Adaptive Immune ◽  
Age Related ◽  
Hsv 1

Immune function declines with age, leading to an increased vulnerability to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to infections remain to be fully elucidated. In the present study, we used a mouse model of intranasal infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs through the nasal route causing pneumonia, a serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic innate and adaptive immune response to infection; and (ii) correlated the level and type of immune response to protection against HSV-1 infection. Compared to young and adult mice, aged mice displayed: (i) increased basal level activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-1, MHC-II and CD80/86; and (iii) decreased production of type-I interferons upon stimulation; (iv) a delay in cytokines and chemokines production in the lungs; and (v) an impairment in function (CD107 and IFN-g production) of HSV-specific CD8+ T cells. These impairment in innate and adaptive immune responses in aged mice following intranasal HSV-1 inoculation was associated with symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.

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