scholarly journals Rational Vaccine Design in Times of Emerging Diseases: The Critical Choices of Immunological Correlates of Protection, Vaccine Antigen and Immunomodulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 501
Author(s):  
Virgil Schijns ◽  
Dragomira Majhen ◽  
Peter van der Ley ◽  
Aneesh Thakur ◽  
Artur Summerfield ◽  
...  
Keyword(s):  
Rational Design ◽  
Current Knowledge ◽  
Medical Intervention ◽  
Emerging Diseases ◽  
Vaccine Antigen ◽  
Vaccine Adjuvant ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Life Threatening ◽  
Rational Vaccine Design

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. Finally we review approaches to rational antigen selection and rational vaccine adjuvant design. Harnessing current knowledge on protective immune responses in combination with critical vaccine components is imperative to the prevention of future life-threatening diseases.

scholarly journals Technological approaches to streamline vaccination schedules, progressing towards single-dose vaccines

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Giuseppe Lofano ◽  
Corey P. Mallett ◽  
Sylvie Bertholet ◽  
Derek T. O’Hagan
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Protective Immunity ◽  
Rational Design ◽  
New Technologies ◽  
Current Knowledge ◽  
Medical Intervention ◽  
Immunological Mechanisms ◽  
Spatio Temporal ◽  
Improve Patient

Abstract Vaccines represent the most successful medical intervention in history, with billions of lives saved. Although multiple doses of the same vaccine are typically required to reach an adequate level of protection, it would be advantageous to develop vaccines that induce protective immunity with fewer doses, ideally just one. Single-dose vaccines would be ideal to maximize vaccination coverage, help stakeholders to greatly reduce the costs associated with vaccination, and improve patient convenience. Here we describe past attempts to develop potent single dose vaccines and explore the reasons they failed. Then, we review key immunological mechanisms of the vaccine-specific immune responses, and how innovative technologies and approaches are guiding the preclinical and clinical development of potent single-dose vaccines. By modulating the spatio-temporal delivery of the vaccine components, by providing the appropriate stimuli to the innate immunity, and by designing better antigens, the new technologies and approaches leverage our current knowledge of the immune system and may synergize to enable the rational design of next-generation vaccination strategies. This review provides a rational perspective on the possible development of future single-dose vaccines.

scholarly journals Immune predictors of mortality following RNA virus infection

2019 ◽  
Author(s):  
Jessica B Graham ◽  
Jessica L Swarts ◽  
Vineet D Menachery ◽  
Lisa E Gralinski ◽  
Alexandra Schäfer ◽  
...  
Keyword(s):  
Virus Infection ◽  
Clinical Outcomes ◽  
Rna Virus ◽  
Severe Disease ◽  
Virus Infections ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Rational Vaccine Design ◽  
Immune Phenotypes ◽  
Common Infections

Abstract Background Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines, as well as the early identification of individuals with the highest risk that may require supportive treatment. Methods We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, SARS-coronavirus, and West Nile virus. Results CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality following infection and strains exhibiting no mortality. We then used comprehensive pre-infection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection. Conclusions These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.

scholarly journals Immunological surrogate endpoints of COVID-2019 vaccines: the evidence we have versus the evidence we need

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Pengfei Jin ◽  
Jingxin Li ◽  
Hongxing Pan ◽  
Yanfei Wu ◽  
Fengcai Zhu
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Surrogate Endpoints ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Efficacy Trials ◽  
Review Current

AbstractIn response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.

Ion Channel Remodelling in Atrial Fibrillation

2011 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Niels Voigt ◽  
Dobromir Dobrev ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ion Channel ◽  
Antiarrhythmic Drugs ◽  
Current Knowledge ◽  
Bleeding Complications ◽  
Large Size ◽  
Cardiovascular Morbidity And Mortality ◽  
Number Of Patients ◽  
Life Threatening ◽  
Underlying Mechanisms

Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. Present drugs used for the therapy of AF (antiarrhythmics and anticoagulants) have major limitations, including incomplete efficacy, risks of life-threatening proarrhythmic events and bleeding complications. Non-pharmacological ablation procedures are efficient and apparently safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. These limitations largely result from limited knowledge about the underlying mechanisms of AF and there is a hope that a better understanding of the molecular basis of AF may lead to the discovery of safer and more effective therapeutic targets. This article reviews the current knowledge about AF-related ion-channel remodelling and discusses how these alterations might affect the efficacy of antiarrhythmic drugs.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

scholarly journals The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy
Keyword(s):  
Proteolytic Activity ◽  
Current Knowledge ◽  
Current Therapy ◽  
Calcium Dependent ◽  
Administration Routes ◽  
Life Threatening ◽  
Living Organisms ◽  
Almost All ◽  
Open Question ◽  
Calpain Inhibitors

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?

scholarly journals Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 551
Author(s):  
Sara Scarpini ◽  
Francesca Morigi ◽  
Ludovica Betti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Human Cytomegalovirus ◽  
Congenital Infection ◽  
Health Concern ◽  
Live Vaccines ◽  
Target Populations ◽  
Immune Correlates ◽  
Common Causes ◽  
The Status ◽  
Life Threatening

Human cytomegalovirus (hCMV) is one of the most common causes of congenital infection in the post-rubella era, representing a major public health concern. Although most cases are asymptomatic in the neonatal period, congenital CMV (cCMV) disease can result in permanent impairment of cognitive development and represents the leading cause of non-genetic sensorineural hearing loss. Moreover, even if hCMV mostly causes asymptomatic or pauci-symptomatic infections in immunocompetent hosts, it may lead to severe and life-threatening disease in immunocompromised patients. Since immunity reduces the severity of disease, in the last years, the development of an effective and safe hCMV vaccine has been of great interest to pharmacologic researchers. Both hCMV live vaccines—e.g., live-attenuated, chimeric, viral-based—and non-living ones—subunit, RNA-based, virus-like particles, plasmid-based DNA—have been investigated. Encouraging data are emerging from clinical trials, but a hCMV vaccine has not been licensed yet. Major difficulties in the development of a satisfactory vaccine include hCMV’s capacity to evade the immune response, unclear immune correlates for protection, low number of available animal models, and insufficient general awareness. Moreover, there is a need to determine which may be the best target populations for vaccine administration. The aim of the present paper is to examine the status of hCMV vaccines undergoing clinical trials and understand barriers limiting their development.

scholarly journals Tick Importin-α Is Implicated in the Interactome and Regulome of the Cofactor Subolesin

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 457
Author(s):  
Sara Artigas-Jerónimo ◽  
Margarita Villar ◽  
Alejandro Cabezas-Cruz ◽  
Grégory Caignard ◽  
Damien Vitour ◽  
...  
Keyword(s):  
Rational Design ◽  
Fat Body ◽  
Animal Health ◽  
Direct Interaction ◽  
Vaccine Antigen ◽  
Tick Feeding ◽  
Interacting Protein ◽  
Expression Levels ◽  
Importin Α

Ticks and tick-borne diseases (TBDs) represent a burden for human and animal health worldwide. Currently, vaccines constitute the safest and most effective approach to control ticks and TBDs. Subolesin (SUB) has been identified as a vaccine antigen for the control of tick infestations and pathogen infection and transmission. The characterization of the molecular function of SUB and the identification of tick proteins interacting with SUB may provide the basis for the discovery of novel antigens and for the rational design of novel anti-tick vaccines. In the present study, we used the yeast two-hybrid system (Y2H) as an unbiased approach to identify tick SUB-interacting proteins in an Ixodes ricinus cDNA library, and studied the possible role of SUB as a chromatin remodeler through direct interaction with histones. The Y2H screening identified Importin-α as a potential SUB-interacting protein, which was confirmed in vitro in a protein pull-down assay. The sub gene expression levels in tick midgut and fat body were significantly higher in unfed than fed female ticks, however, the importin-α expression levels did not vary between unfed and fed ticks but tended to be higher in the ovary when compared to those in other organs. The effect of importin-α RNAi was characterized in I. ricinus under artificial feeding conditions. Both sub and importin-α gene knockdown was observed in all tick tissues and, while tick weight was significantly lower in sub RNAi-treated ticks than in controls, importin-α RNAi did not affect tick feeding or oviposition, suggesting that SUB is able to exert its function in the absence of Importin-α. Furthermore, SUB was shown to physically interact with histone 4, which was corroborated by protein pull-down and western blot analysis. These results confirm that by interacting with numerous tick proteins, SUB is a key cofactor of the tick interactome and regulome. Further studies are needed to elucidate the nature of the SUB-Importin-α interaction and the biological processes and functional implications that this interaction may have.

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