Immune responses during cutaneous and visceral leishmaniasis

Parasitology ◽  
2014 ◽  
Vol 141 (12) ◽  
pp. 1544-1562 ◽  
Author(s):  
LUKASZ KEDZIERSKI ◽  
KRYSTAL J. EVANS
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
Current Treatment ◽  
Acquired Immunity ◽  
Insect Vector ◽  
Protozoan Parasites ◽  
Human Immune Response ◽  
Human Immune ◽  
Significant Health

SUMMARYLeishmaniaare protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world, resulting in an estimated 1·3 million new cases and 30 000 deaths annually. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective in several endemic regions. To date there is no vaccine against leishmaniasis, although extensive evidence from studies in animal models indicates that solid protection can be achieved upon immunization. This review focuses on immune responses toLeishmaniain both cutaneous and visceral forms of the disease, pointing to the complexity of the immune response and to a range of evasive mechanisms utilized by the parasite to bypass those responses. The amalgam of innate and acquired immunity combined with the paucity of data on the human immune response is one of the major problems currently hampering vaccine development and implementation.

Leishmaniavaccines: progress and problems

Parasitology ◽  
2006 ◽  
Vol 133 (S2) ◽  
pp. S87-S112 ◽  
Author(s):  
L. KEDZIERSKI ◽  
Y. ZHU ◽  
E. HANDMAN
Keyword(s):  
Animal Models ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Current Treatment ◽  
Insect Vector ◽  
Protozoan Parasites ◽  
Vaccine Research ◽  
Subsequent Infection ◽  
Successful Vaccine ◽  
Significant Health

Leishmaniaare protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding ofLeishmaniapathogenesis and generation of host protective immunity, together with the completedLeishmaniagenome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation.

scholarly journals Evaluating use cases for human challenge trials in accelerating COVID-19 vaccine development

2020 ◽  
Author(s):  
Linh Chi Nguyen ◽  
Christopher W Bakerlee ◽  
T Greg McKelvey ◽  
Sophie M Rose ◽  
Alexander J Norman ◽  
...  
Keyword(s):  
Immune Response ◽  
Potential Role ◽  
Vaccine Development ◽  
Use Cases ◽  
Challenge Virus ◽  
Correlates Of Protection ◽  
Practical Guidelines ◽  
Human Immune Response ◽  
Human Immune

Recently, human challenge trials (HCTs) have been proposed as a means to accelerate the development of an effective SARS-CoV-2 vaccine. In this paper, we discuss the potential role for such studies in the current COVID-19 pandemic. First, we present three scenarios in which HCTs could be useful: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We go on to outline the practical limitations of HCTs in these scenarios. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be vastly beneficial and, thus, the option of using HCTs to accelerate COVID-19 vaccine development should be preserved. To this end, we recommend an immediate, coordinated effort by all stakeholders to (1) establish ethical and practical guidelines for the use of HCTs for COVID-19; (2) take the first steps toward an HCT, including preparing challenge virus under GMP and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs amid the evolving pandemic.

scholarly journals Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development

2020 ◽  
Author(s):  
Linh Chi Nguyen ◽  
Christopher W Bakerlee ◽  
T Greg McKelvey ◽  
Sophie M Rose ◽  
Alexander J Norman ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Use Cases ◽  
Stages Of Development ◽  
Challenge Virus ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Human Immune Response ◽  
Human Immune ◽  
Potential Use

Abstract Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be extremely beneficial. Therefore, the option of conducting HCTs to accelerate SARS-CoV-2 vaccine development should be preserved. As HCTs require many months of preparation, we recommend an immediate effort to (1) establish guidelines for HCTs for COVID-19; (2) take the first steps toward HCTs, including preparing challenge virus and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs.

scholarly journals Immune Response toward Mycobacterium Tuberculosis Infection

2020 ◽  
Vol 2 (2) ◽  
pp. 77-87
Author(s):  
Abdi Dzul Ikram Hasanuddin ◽  
Nanang Roswita ◽  
Ivan Virnanda Amu
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Adaptive Immune ◽  
Human Immune Response ◽  
Exogenous Factors ◽  
Human Immune ◽  
Microfold Cells

Understanding the human immune response toward Mycobacterium tuberculosis infection is important for controlling its infection. Its transmission through the air consists of "droplets nuclei" containing TB bacilli. After initial infection, the human body will provide diverse immune responses and will determine different clinico-histopathologic finding. This response starts from innate immunity that consists of phagocytosis by distal alveolar macrophages or nasal microfold cells, then will be continued by dendritic cells to be transferred to mediastinal lymph nodes to induced adaptive immune responses. This response is mediated by cells through IFN- γ signaling which will enhance phagocytosis. If this response is effective, there will be a latent infection with an initial histopathological finding of caseosa granulomas and predominantly followed by chronic granulomas. In a few cases, it can be reactivated via the IL-10 activation pathway and exogenous factors, it will induce a great adaptive immune reaction and provide more severe clinico-histopathological manifestation. The existence of the human body's immune response to Mycobacterium tuberculosis, etiher innate or adaptive immunity will determine the clinical course and pathology that will occur.

scholarly journals Variation in Gamma Interferon Responses to Different Infecting Strains of Mycobacterium tuberculosis in Acid-Fast Bacillus Smear-Positive Patients and Household Contacts in Antananarivo, Madagascar

2010 ◽  
Vol 17 (7) ◽  
pp. 1094-1103 ◽  
Author(s):  
Niaina Rakotosamimanana ◽  
Vaomalala Raharimanga ◽  
Soa Fy Andriamandimby ◽  
Jean-Louis Soares ◽  
T. Mark Doherty ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Gamma Interferon ◽  
Clinical Strains ◽  
Household Contacts ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Index Cases

ABSTRACT The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-γ) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-γ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-γ responses with the spoligotype of the infecting clinical strains showed that “modern” M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-γ responses than “ancient” strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies.

scholarly journals Temperate Bacteriophages—The Powerful Indirect Modulators of Eukaryotic Cells and Immune Functions

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1013
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Ewa Jończyk-Matysiak ◽  
Alicja Węgrzyn ◽  
Grzegorz Węgrzyn ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Modulation ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Mammalian Host ◽  
Immune Functions ◽  
Human Immune Response ◽  
Human Immune ◽  
Biological Entities

Bacteriophages are natural biological entities that limit the growth and amplification of bacteria. They are important stimulators of evolutionary variability in bacteria, and currently are considered a weapon against antibiotic resistance of bacteria. Nevertheless, apart from their antibacterial activity, phages may act as modulators of mammalian immune responses. In this paper, we focus on temperate phages able to execute the lysogenic development, which may shape animal or human immune response by influencing various processes, including phagocytosis of bacterial invaders and immune modulation of mammalian host cells.

scholarly journals Human Immune Response to COVID-19 Infection and Potential Role of Chloroquine Family of Drugs

2020 ◽  
Author(s):  
Sunita Singh ◽  
Chandra Shekharaiah PS ◽  
Vishal Paul ◽  
Santosh Kodgire ◽  
Shivbachan Kushwaha ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clinical Studies ◽  
Task Force ◽  
The Body ◽  
European Medicines Agency ◽  
Regulatory Bodies ◽  
Human Immune Response ◽  
Human Immune ◽  
Set Up

Currently, world is witnessing a massive morbidity and mortality due to COVID-19 pandemic.  A novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The virus enters inside the body and infect the cells through angiotensin-converting enzyme 2 (ACE2) receptor. The S1 protein of SARS-CoV-2 binds to the ACE2 receptor which results in endocytosis and transfer of virus into endosomes of body cells. Entry of SARS-CoV-2 results in activation of innate immune responses first followed by adaptive immune responses. The effective host immune responses are crucial to control and prevent viral infection. However, excessive production of proinflammatory cytokines and decrease in number of T-lymphocytes are the major reasons associated with severity of COVID-19. Therapies and drugs that can modulate the immune responses appropriately may play a crucial role to control and prevent the progression of disease. Chloroquine (CQ) and hydroxychloroquine (HCQ) have anti-inflammatory, immunomodulatory, antitumor, antimicrobial and antithrombotic effects. These drugs have already been registered in many countries to treat arthritis, lupus and malaria. The treatment responses of COVID-19 patients to these drugs have been found positive in some cases and clinical studies are underway for evaluating these drugs for the same. However, there are some serious side effects and health hazards associated. Many regulatory bodies are demanding more conclusive data on efficacy and safety from the clinical studies. Moreover, some regulatory bodies such as Food and Drug Administration (FDA) and European Medicines Agency (EMA) have recommended to use these drugs in emergency and chronic situation to treat critically ill COVID-19 patients under doctor’s supervision with all issued guidelines. The national task force (NTF) set up by Indian Council of Medical Research has recommended high risk individuals to take HCQ for prophylaxis. This review summarizes human immune response and various aspects of CQ and HCQ with special reference to COVID-19.

scholarly journals Assessing the human immune response to SARS-CoV-2 variants

2021 ◽  
Vol 27 (4) ◽  
pp. 571-572 ◽  
Author(s):  
Roberto Burioni ◽  
Eric J. Topol
Keyword(s):  
Immune Response ◽  
Human Immune Response ◽  
Human Immune

scholarly journals Approaches to Modelling the Human Immune Response in Transition of Candidates from Research to Development

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Diane Williamson
Keyword(s):  
Immune Response ◽  
Human Immune Response ◽  
Human Immune ◽  
Animal Rule

This review considers the steps required to evaluate a candidate biodefense vaccine or therapy as it emerges from the research phase, in order to transition it to development. The options for preclinical modelling of efficacy are considered in the context of the FDA’s Animal Rule.

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