scholarly journals Nature of Acquired Immune Responses, Epitope Specificity and Resultant Protection from SARS-CoV-2

2021 ◽  
Vol 11 (12) ◽  
pp. 1253
Author(s):  
Reginald M. Gorczynski ◽  
Robyn A. Lindley ◽  
Edward J. Steele ◽  
Nalin Chandra Wickramasinghe
Keyword(s):  
Viral Infection ◽  
Vaccine Development ◽  
Respiratory Infections ◽  
Resistance Mechanisms ◽  
Global Response ◽  
Host Protection ◽  
Immune Resistance ◽  
Mucosal Surfaces ◽  
Immunological Research ◽  
Acquired Immune Responses

The primary global response to the SARS-CoV-2 pandemic has been to bring to the clinic as rapidly as possible a number of vaccines that are predicted to enhance immunity to this viral infection. While the rapidity with which these vaccines have been developed and tested (at least for short-term efficacy and safety) is commendable, it should be acknowledged that this has occurred despite the lack of research into, and understanding of, the immune elements important for natural host protection against the virus, making this endeavor a somewhat unique one in medical history. In contrast, as pointed out in the review below, there were already important past observations that suggested that respiratory infections at mucosal surfaces were susceptible to immune clearance by mechanisms not typical of infections caused by systemic (blood-borne) pathogens. Accordingly, it was likely to be important to understand the role for both innate and acquired immunity in response to viral infection, as well as the optimum acquired immune resistance mechanisms for viral clearance (B cell or antibody-mediated, versus T cell mediated). This information was needed both to guide vaccine development and to monitor its success. We have known that many pathogens enter into a quasi-symbiotic relationship with the host, with each undergoing sequential change in response to alterations the other makes to its presence. The subsequent evolution of viral variants which has caused such widespread concern over the last 3–6 months as host immunity develops was an entirely predictable response. What is still not known is whether there will be other unexpected side-effects of the deployment of novel vaccines in humans which have yet to be characterized, and, if so, how and if these can be avoided. We conclude by remarking that to ignore a substantial body of well-attested immunological research in favour of expediency is a poor way to proceed.

SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Common Knowledge ◽  
Herd Immunity ◽  
Life Quality ◽  
Host Cells ◽  
System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

scholarly journals The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 380
Author(s):  
Bonnie L Quigley ◽  
Peter Timms
Keyword(s):  
Immune Response ◽  
Chlamydial Infection ◽  
Vaccine Development ◽  
Interleukin 17 ◽  
Phascolarctos Cinereus ◽  
Post Vaccination ◽  
Research Systems ◽  
Cytokine Levels ◽  
Nucleic Acid Assay ◽  
Immunological Research

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

The Role of Sialylation in Respiratory Viral Infection and Treatment

2021 ◽  
Vol 28 ◽  
Author(s):  
Harrison Steele ◽  
Andrew J. Tague ◽  
Danielle Skropeta
Keyword(s):  
Viral Infection ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Sialic Acids ◽  
Infection Cycle ◽  
Respiratory Viral Infection ◽  
Development Of Resistance ◽  
High Infection ◽  
Cell Expression

: Respiratory infections caused by viruses such as influenza and coronavirus are a serious global problem due to their high infection rates and potential to spark pandemics, such as the current COVID-19 pandemic. Although preventing these infections by using vaccines has been the most successful strategy to date, effective vaccines are not always available. Therefore, developing broad-spectrum anti-viral drugs to treat such infections is essential, especially in the case of immunocompromised patients, or for outbreaks of novel virus strains. Sialic acids have been highlighted as a key molecule in the viral infection cycle, with terminally sialylated glycans acting as a target for several viral proteins involved in infection, particularly respiratory infection. Inhibitors of one such protein, neuraminidase, are the only anti-influenza drugs currently on the market. Problems with neuraminidase inhibitors, including development of resistance and a relatively narrow spectrum of activity, drive the need for an improved understanding of the viral infection cycle and the development of more resilient, broader-spectrum anti-viral treatments. Hence, this review outlines the various roles played by sialic acids in respiratory viral infection and provides examples of drugs that exploit sialic acids to inhibit viral infections. It has been concluded that drugs targeting host cell expression of sialic acid could be especially well suited to inhibiting a broad spectrum of respiratory infections. This warrants the continued design and improvement of such drugs in an attempt to lessen the burden of respiratory infections.

scholarly journals Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 407 ◽  
Author(s):  
Emily Hays ◽  
Benjamin Bonavida
Keyword(s):  
Nitric Oxide ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Tumor Regression ◽  
Cytotoxic T Cells ◽  
Resistance Mechanisms ◽  
Binding Activity ◽  
No Donors ◽  
Dna Binding Activity ◽  
Immune Resistance

In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression.

scholarly journals Renal control of disease tolerance to malaria

2019 ◽  
Vol 116 (12) ◽  
pp. 5681-5686 ◽  
Author(s):  
Susana Ramos ◽  
Ana Rita Carlos ◽  
Balamurugan Sundaram ◽  
Viktoria Jeney ◽  
Ana Ribeiro ◽  
...  
Keyword(s):  
Control Mechanism ◽  
Damage Control ◽  
Kidney Injury ◽  
Resistance Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Disease Tolerance ◽  
Host Protection ◽  
Ferritin H ◽  
Transcription Factor Nuclear Factor

Malaria, the disease caused byPlasmodiumspp. infection, remains a major global cause of morbidity and mortality. Host protection from malaria relies on immune-driven resistance mechanisms that killPlasmodium. However, these mechanisms are not sufficient per se to avoid the development of severe forms of disease. This is accomplished instead via the establishment of disease tolerance to malaria, a defense strategy that does not targetPlasmodiumdirectly. Here we demonstrate that the establishment of disease tolerance to malaria relies on a tissue damage-control mechanism that operates specifically in renal proximal tubule epithelial cells (RPTEC). This protective response relies on the induction of heme oxygenase-1 (HMOX1; HO-1) and ferritin H chain (FTH) via a mechanism that involves the transcription-factor nuclear-factor E2-related factor-2 (NRF2). As it accumulates in plasma and urine during the blood stage ofPlasmodiuminfection, labile heme is detoxified in RPTEC by HO-1 and FTH, preventing the development of acute kidney injury, a clinical hallmark of severe malaria.

scholarly journals Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 272
Author(s):  
Andrew Hildreth ◽  
Timothy O’Sullivan
Keyword(s):  
Viral Infection ◽  
Cytokine Production ◽  
Lymphocyte Subsets ◽  
Current Knowledge ◽  
Critical Role ◽  
Lymphoid Cells ◽  
T Cell Subsets ◽  
Antiviral Responses ◽  
Host Protection ◽  
Lymphocyte Responses

Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Recent discoveries have demonstrated that tissue-resident lymphocyte subsets, comprised of innate lymphoid cells (ILCs) and unconventional T cells, have vital roles in the initiation of primary antiviral responses. Via direct and indirect mechanisms, ILCs and unconventional T cell subsets play a critical role in the ability of the immune system to mount an effective antiviral response through potent early cytokine production. In this review, we will summarize the current knowledge of tissue-resident lymphocytes during initial viral infection and evaluate their redundant or nonredundant contributions to host protection or virus-induced pathology.

scholarly journals Dendritic Cells/Macrophages-Targeting Feature of Ebola Glycoprotein and its Potential as Immunological Facilitator for Antiviral Vaccine Approach

2019 ◽  
Vol 7 (10) ◽  
pp. 402
Author(s):  
Titus Abiola Olukitibi ◽  
Zhujun Ao ◽  
Mona Mahmoudi ◽  
Gary A. Kobinger ◽  
Xiaojian Yao
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Approach ◽  
Vaccine Approach ◽  
Acquired Immune Responses ◽  
Diverse Virus

In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP.

Respiratory infections caused by Haemophilus influenzae β-lactamase positive carrying blaTEM gene

2020 ◽  
Vol 30 (Supplement_2) ◽  
Author(s):  
J Valério ◽  
H Ferreira ◽  
C Chaves ◽  
F Rodrigues ◽  
N Osório
Keyword(s):  
Antibiotic Therapy ◽  
Respiratory Infections ◽  
Clinical Pathology ◽  
Resistance Mechanisms ◽  
Important Data ◽  
Ampicillin Resistance ◽  
Phenotypic Profile ◽  
Antimicrobial Susceptibility Profile ◽  
Activity Screening ◽  
Etiological Agents

Abstract Introduction One of the main etiological agents of respiratory infections is H. Influenzae. The group of antibiotics most used to the treatment of H. influenzae infections is β-lactams. The most common β-lactam resistance is to ampicillin, characterized by the production of TEM (95%) and ROB (5%) β-lactamases, designated enzymatic resistance. Objectives Characterize the susceptibility profile of H. influenzae to β-lactam antibiotics, to evaluate the enzymatic resistance by the β-lactamase production and to correlate the phenotypic profile with the presence of the blaTEM. Methodology Total of 152 isolates of H. influenzae from respiratory infections were evaluated: 88 from expectorations, 56 from bronchial aspirates and 8 from bronchoalveolar lavage, collected in Clinical Pathology Service of Centro Hospitalar e Universitário de Coimbra. The results of the antimicrobial susceptibility profile and the β-lactamase screening were also provided. In order to investigate the blaTEM, DNA was extracted from the isolates and the detection was performed using the PCR technique. Results The prevalence of the blaTEM in the isolates was 31.6%, of these 33.3% showed resistance to ampicillin and 57.9% were positive in β-lactamase activity screening and blaTEM carriers. There was a statistically significance between the presence of the gene with ampicillin resistance and β-lactamase activity screening. Conclusion β-lactamase TEM production was the main mechanism of enzymatic resistance which demonstrates the high spread of the blaTEM among isolates of H. influenzae. The results found suggest that the negative strains for this β-lactamase but that presented β-lactamases with activity and resistance to β-lactams should have other β-lactamases as ROB or others. However strains with β-lactamase negative should have other mechanisms promoting the resistance as PBP3. This study provides important data on the antibiotic therapy, to minimize the expression of resistance mechanisms and problems associated with treatment.

scholarly journals 2634. Human Metapneumovirus in a Children’s Hospital: It Should Get More Attention

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S920-S920
Author(s):  
Nellie Said ◽  
Wendi Gornick ◽  
Beth Huff ◽  
Jasjit Singh
Keyword(s):  
Disease Surveillance ◽  
Vaccine Development ◽  
Respiratory Infections ◽  
Human Metapneumovirus ◽  
Time Period ◽  
Potential Vaccine ◽  
Syncytial Virus ◽  
Viral Respiratory Infections ◽  
Hospital Acquired ◽  
Viral Respiratory

Abstract Background Viral respiratory infections are a major cause of hospitalization and intensive care unit (ICU) admission to children’s hospitals. Rates of respiratory syncytial virus (RSV) and influenza are closely tracked due to their known morbidity. We had previously observed over one season that human metapneumovirus (hMPV)-infected children have high rates of hospitalizations and ICU admissions, particularly those with chronic lung disease (CLD). We expanded our data to include an additional 5 seasons to compare rates of hospitalizations and hospital-acquired infections (HAIs) due to hMPV, RSV and influenza. Methods During the 2014–2019 winter viral seasons, hMPV, RSV and influenza infections were tracked through both PCR testing (Biofire Respiratory Panel) and DFA testing (D3 Ultra DFA Respiratory Virus Screening & ID Kit; Diagnostic Hybrids). For hMPV admissions, rates of hospitalizations, ICU admissions, HAIs and mortalities were assessed and compared with RSV and influenza admissions. Retrospective data were used to study patients infected with hMPV. Results During the winter seasons of 2014–2019, the rates of hospitalization due to hMPV were significantly higher than both RSV and influenza (Figure 1). ICU admissions and HAIs for hMPV were similar to RSV and influenza (Figures 2 and 3). There were 9 deaths over this time period; 5 due to RSV, 3 due to influenza and 1 due to hMPV. The proportion of deaths due to hMPV compared with RSV and influenza was similar (P = 0.54, 0.89, respectively). Of the 315 total admissions with hMPV, 43 (13.7%) had CLD and 13 (4.1%) were tracheostomy dependent. Among 67 hMPV ICU admissions from 2014–2019, 56 (84%) had an underlying medical diagnosis, 25 (37%) had CLD, 13 (19%) had tracheostomies, and 17 (25%) required mechanical ventilation. The average age of hMPV infected children in our ICU is 4 years 1 month. Conclusion Our large descriptive study of hMPV-infected children over 6 seasons showed higher rates of hospitalization compared with RSV and influenza, similar ICU and HAI rates, and similar rates of mortality. ICU admitted children often had associated co-morbidities, including CLD. Further studies for focused disease surveillance and potential vaccine development for high-risk children are needed. Disclosures All authors: No reported disclosures.

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