scholarly journals Late-Relapsing Hepatitis after Yellow Fever

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 222 ◽  
Author(s):  
Izabela Maurício Rezende ◽  
Leonardo Soares Pereira ◽  
Jordana Rodrigues Barbosa Fradico ◽  
Marcelo Antônio Pascoal Xavier ◽  
Pedro Augusto Alves ◽  
...  
Keyword(s):  
Immune Response ◽  
Yellow Fever ◽  
Neutralizing Antibodies ◽  
Laboratory Tests ◽  
Cell Damage ◽  
Viral Persistence ◽  
Response Profile ◽  
Liver Transaminases ◽  
Hepatic Cytolysis

One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.

REINFECTION AFTER SARS-COV2 INFECTION: A LOOMING CONCERN

2020 ◽  
Vol 8 (Spl-1-SARS-CoV-2) ◽  
pp. S114-S118
Author(s):  
Akshay Kumar ◽  
◽  
Nimisha Shiwalkar ◽  
Juber Dastagir Shaikh ◽  
Roopvir Kaur ◽  
...  
Keyword(s):  
Immune Response ◽  
Polymerase Chain Reaction ◽  
Literature Review ◽  
Neutralizing Antibodies ◽  
Chain Reaction ◽  
Prevention And Treatment ◽  
Polymerase Chain ◽  
Case Presentations ◽  
Positive Results

Many unanswered questions remain about COVID-19 infection caused by SARS-CoV-2 coronavirus. One such looming concern is the possibility of reinfection of recovered cases. We conducted a literature review on various aspects of this possibility, including the case presentations of relapsed/re-infected patients, the immune response of production of neutralizing antibodies, immunity in response to coronavirus during SARS-CoV2 and MERS, possibility of false-positive results of real-time polymerase chain reaction. We concluded that further studies are required to establish whether relapse or reinfection is possible firmly. However, these possibilities point towards the needs of change in the protocol of isolation, quarantine, and discharge. It also undermines the role of the upcoming vaccine in disease prevention and treatment.

scholarly journals The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination

2008 ◽  
Vol 205 (4) ◽  
pp. 981-992 ◽  
Author(s):  
Ren-Huan Xu ◽  
Matthew Cohen ◽  
Yong Tang ◽  
Eric Lazear ◽  
J. Charles Whitbeck ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Traditional Approach ◽  
Binding Protein ◽  
Type I ◽  
Type I Ifn ◽  
Type I Ifns ◽  
Recombinant Type ◽  
Natural Target

Nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. Orthopoxviruses (OPVs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ECTV; an agent of mousepox), encode immune response modifiers (IRMs) that can increase virulence by decreasing the host immune response. We show that one of these IRMs, the type I interferon (IFN) binding protein (bp) of ECTV, is essential for ECTV virulence and is a natural target of the antibody response. More strikingly, we demonstrate that immunization with recombinant type I IFN bp protects mice from lethal mousepox. Collectively, our experiments have important implications for our understanding of the role of IRMs in OPV virulence and of type I IFNs in OPV infections. Furthermore, our work provides proof of concept that effective antiviral vaccines can be made to prevent disease by targeting virulence factors as an alternative to the traditional approach that attempts to prevent infection by virus neutralization.

scholarly journals Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

2019 ◽  
Author(s):  
Crisanta Serrano-Collazo ◽  
Erick X. Pérez-Guzmán ◽  
Petraleigh Pantoja ◽  
Mariah A. Hassert ◽  
Idia V. Rodríguez ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Denv Infection ◽  
Effector Memory ◽  
Zikv Infection ◽  
Humoral Immune ◽  
Significant Control

AbstractPrior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe disease upon secondary heterologous DENV infection. Here we show that the length of time between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. We identified limited but significant differences in the magnitude of the early humoral immune response associated with a period of twelve months but not three months of DENV convalescence. However, their role limiting ZIKV replication is not conclusive. There was no evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. We are also showing that the significant differences among groups may be linked to a pre-existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV infection) and to an early and continuous expansion of the CD4+ effector memory cells early on after ZIKV infection. Those significant differences were associated with a period of 12 months after DENV infection that were not observed in a span of 3-months. These results suggest that there is a window of optimal cross-protection between ZIKV and DENV with significant consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs among others.Author SummarySince its introduction in the Americas region ZIKV virus has been associated to severe birth defects. One of the questions that remains open is the role of previous dengue or any other flavivirus immunity in the pathogenesis of ZIKV and more important, if the time elapse between DENV and ZIKV play a role enhancing ZIKV pathogenesis as it is the case for subsequent DENV infections. On this work, using NHP as a model we compared the effect of a period of 12 months vs. a period of 3 months of DENV immunity in the outcome of ZIKV infection. We found that previous DENV infection, at any of the tested period of time do not induce ZIKV enhancement. More relevant are showing that when the two infection occurs at least one year apart the preexisting DENV immunity is better at controlling ZIKV replication and that the role of the neutralizing antibodies is very limited. On the contrary our results suggest that early after ZIKV infection the cellular immune response, may plays a predominant role. Our findings have critical relevance to understand the dynamic interaction between these two flavivirus, their pathogenies, diagnosis and vaccine design.

scholarly journals A prevaccination validated network that drives the breadth of the protective neutralizing antibody response following Dengue Vaccine TV003 immunization

2021 ◽  
Author(s):  
Adam-Nicolas Pelletier ◽  
Gabriela Pacheco Sanchez ◽  
Mark Watson ◽  
Abdullah Izmirly ◽  
Tiziana Di Pucchio ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Inflammasome Activation ◽  
Proinflammatory Response ◽  
Protective Antibody ◽  
Secondary Bile Acids

Development of fully protective dengue virus (DV) vaccines has been problematic as infection with DV requires a broad antibody immune response that targets all 4 possible serotypes. Herein, we used an integrated systems vaccinology approach to identify prevaccination features that allow the development of fully protective DV-specific antibody responses. This approach allowed us to identify a transcription network in a subset of monocytes defined by the expression of CD68 and downstream of specific pro- and anti-inflammatory cytokines. Moreover, we identified metabolites as drivers of an immune response that induced neutralizing antibodies to the 4 DV serotypes. Specifically, PC/PE drove the production of TGF-B in CD68 low monocytes, which was a positive correlate of the protective antibody response. In contrast, primary and secondary bile acids triggered a proinflammatory response downstream of TGR5 signaling and inflammasome activation in CD68 high monocytes, which was associated to a non-protective antibody response. These features were validated in vitro in primary myeloid cells. Our results highlight the role of cell and systemic metabolism as regulators of protective immune responses to vaccination, and that systems vaccinology is a key tool to identify such mechanisms.

scholarly journals Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Emily N. Gallichotte ◽  
Ellen F. Young ◽  
Thomas J. Baric ◽  
Boyd L. Yount ◽  
Stefan W. Metz ◽  
...  
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Yellow Fever Virus ◽  
Viral Envelope ◽  
Chimeric Virus ◽  
Domain Iii ◽  
Major Target

ABSTRACT Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIII-targeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIII-specific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines.

scholarly journals Sepsis and ARDS: The Dark Side of Histones

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zhiheng Xu ◽  
Yongbo Huang ◽  
Pu Mao ◽  
Jianrong Zhang ◽  
Yimin Li
Keyword(s):  
Neutralizing Antibodies ◽  
Cell Damage ◽  
Activated Protein C ◽  
Basic Structure ◽  
The Body ◽  
Dark Side ◽  
Protective Effects ◽  
Extracellular Histones ◽  
Physical Challenges

Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.

scholarly journals Studies on the role of the host immune response in recovery from Friend virus leukemia. I. Antiviral and antileukemia cell antibodies.

1976 ◽  
Vol 143 (1) ◽  
pp. 73-84 ◽  
Author(s):  
B Chesebro ◽  
K Wehrly
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Neutralizing Antibodies ◽  
Passive Transfer ◽  
Leukemia Cells ◽  
Friend Virus ◽  
Humoral Immune ◽  
Virus Leukemia

The humoral immune response to Friend virus leukemia was studied in congenic F1 mice differing in their incidence of recovery from leukemia. Antiviral neutralizing antibodies rose in titer in vivo concurrently with disappearance of viremia and fall in spleen virus levels. Cytotoxic antileukemia cell antibodies also appeared at this time. Passive transfer of these antibodies could inactivate low numbers of leukemia cells in vivo; however, mice of both high and low recovery genotypes produced antibodies in equal titer and recovered from viral infection in spite of striking differences in recovery from leukemic splenomegaly. Mice lacking C57BL genes did not produce antibodies or recover from viremia except in rare instances. Recovery from splenomegaly was found to be influenced by three or more C57BL genes independent of the H-2 complex.

The Impact of Defective Viruses on Infection and Immunity

2019 ◽  
Vol 6 (1) ◽  
pp. 547-566 ◽  
Author(s):  
Emmanuelle Genoyer ◽  
Carolina B. López
Keyword(s):  
Immune Response ◽  
Virus Replication ◽  
Innate Immune Response ◽  
Rna Viruses ◽  
Critical Role ◽  
Viral Persistence ◽  
Innate Immune ◽  
Viral Genomes ◽  
The Impact

Defective viral genomes (DVGs) are generated during viral replication and are unable to carry out a full replication cycle unless coinfected with a full-length virus. DVGs are produced by many viruses, and their presence correlates with alterations in infection outcomes. Historically, DVGs were studied for their ability to interfere with standard virus replication as well as for their association with viral persistence. More recently, a critical role for DVGs in inducing the innate immune response during infection was appreciated. Here we review the role of DVGs of RNA viruses in shaping outcomes of experimental as well as natural infections and explore the mechanisms by which DVGs impact infection outcome.

scholarly journals A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate

2020 ◽  
Author(s):  
Lorena Sanchez Felipe ◽  
Thomas Vercruysse ◽  
Sapna Sharma ◽  
Ji Ma ◽  
Viktor Lemmens ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Yellow Fever ◽  
Emergency Response ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Th1 Cell ◽  
Cell Mediated Immune Response ◽  
Further Development ◽  
Fast Acting

AbstractThe explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

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