Antibody Responses in SARS-CoV-2-Exposed and/or Vaccinated Individuals Target Conserved Epitopes from Multiple CoV-2 Antigens.

There is a need to investigate novel strategies in order to create an effective, broadly protective vaccine for current and future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. The currently available vaccines demonstrate compromised efficacy against emerging SARS-CoV-2 variants of concern (VOCs), short-lived immunity, and susceptibility to immune imprinting due to frequent boosting practices. In this study, we examined the specificity of cross-reactive IgG antibody responses in mRNA-vaccinated, AstraZeneca-vaccinated, and unvaccinated donors to identify potentially conserved, cross-reactive epitopes to target in order to create a broadly protective SARS-CoV-2 vaccine.

Mucosal immunization with lipopeptides derived from conserved regions of SARS-CoV-2 antigens induce robust cellular and cross-variant humoral immune responses in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected >600 million people in the ongoing global pandemic. Several variants of the SARS-CoV-2 have emerged in the last >2 years, challenging the continued efficacy of current COVID vaccines. Therefore, there is a crucial need to investigate a highly cross-protective vaccine effective against variants of SARS-CoV-2.

Harnessing Innate Immunity to Treat Infections: Heat-Killed as a Novel Biotherapeutic.

Tuberculosis, caused by (), is a serious and devastating infectious disease worldwide. Approximately a quarter of the world population harbors latent infection without pathological consequences. Exposure of immunocompetent healthy individuals with does not result in active disease in more than 90% individuals, suggesting a defining role of host immunity to prevent and/or clear early infection.

Heterologous immunity induced by 1 generation COVID-19 vaccines and its role in developing a pan-coronavirus vaccine.

Severe acute respiratory syndrome virus-2 (SARS-CoV-2), the causative infectious agent of the COVID-19 pandemic, has led to multiple (4-6) waves of infections worldwide during the past two years. The development of vaccines against SARS-CoV-2 has led to successful mass immunizations worldwide, mitigating the worldwide mortality due the pandemic to a great extent. Yet the evolution of new variants highlights a need to develop a universal vaccine which can prevent infections from all virulent SARS-CoV-2.

Stimulation of toll-like receptor pathways by burn eschar tissue as a possible mechanism for hypertrophic scarring.

Hypertrophic scars (HTS) are a common complication following burn injuries with prolonged inflammation. They do not respond well to current treatment options including mechanical, biomolecular and surgical therapies. Toll-like receptor (TLR) 2 and 4 respond to microbes and damaged endogenous ligands to trigger pro-inflammatory pathways, and they are expressed more in HTS fibroblasts compared to normal skin fibroblasts.

Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections.

The central paradigm of vaccination is to generate resistance to infection by a specific pathogen when the vacinee is re-exposed to that pathogen. This paradigm is based on two fundamental characteristics of the adaptive immune system, specificity and memory. These characteristics come from the clonal specificity of T and B cells and the long-term survival of previously-encountered memory cells which can rapidly and specifically expand upon re-exposure to the same specific antigen.

New therapeutic targets for cancer: the interplay between immune and metabolic checkpoints and gut microbiota.

Transformation and growth of tumor cells are associated with profound alterations in neighbouring cells and their environment, together forming the tumor microenvironment (TME). The TME provides a conducive but complex milieu for the tumors to thrive while incapacitating the immune cells that home there as part of our natural immunosurveillance mechanism. The orchestration of this successful survival strategy by tumor cells is associated with exploitation of numerous metabolic and immune checkpoints, as well as metabolic reprogramming in the tumor cells.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens.

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events.

MUC1 Mucin: A Putative Regulatory (Checkpoint) Molecule of T Cells.

T lymphocytes are at the center of inducing an effective adaptive immune response and maintaining homeostasis. T cell responses are initiated through interactions between antigen presenting cells (APCs) and T cells. The type and strength of signals delivered through the T cell receptor (TCR) may modulate how the cells respond.

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine.

Tuberculosis (TB), an infectious disease caused by (), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults.

New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells.

Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally.

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas.

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine's efficacy.

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb.

Investigation of C-5 alkynyl (alkynyloxy or hydroxymethyl) and/or N-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents.

The resurgence of mycobacterial infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6-10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30-33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (BCG) and Mycobacterium avium], gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) alone and in combination with existing drugs in in vitro assays. Although several compounds exhibited marked inhibitory activity at a higher concentration against Mtb, M.

Symbiotic chemo- and immuno-therapy for hepatitis B and C viruses.

Hepatitis B and C viruses (HBV and HCV), both cause serious chronic infections leading to fatal liver diseases. The prototype therapy for both HBV and HCV was based on IFN-α with or without ribavirin. The advent of direct-acting antivirals (DAA) for both HBV and HCV has remarkably improved the standard of treatment for both infections.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.

Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens.

Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection.

Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations.

Co-incubation with core proteins of HBV and HCV leads to modulation of human dendritic cells.

Hepatitis B and C (HBV and HCV) are hepatotropic viruses in humans with approximately 350 and 170 million chronic carriers respectively. Since both viruses have similar modes of transmission, many people are co-infected. Co-infection is common in intravenous drug users, HIV-positive individuals, and transplant recipients.

Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: a dose and route conundrum.

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens.

4'-Substituted pyrimidine nucleosides lacking 5'-hydroxyl function as potential anti-HCV agents.

Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24).

Alternate reading frame protein (F protein) of hepatitis C virus: paradoxical effects of activation and apoptosis on human dendritic cells lead to stimulation of T cells.

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected individuals due to lack, failure, or inefficiency of generated adaptive immune responses. In a minority of patients, acute infection is followed by viral clearance. The immune correlates of viral clearance are not clear yet but have been extensively investigated, suggesting that multispecific and multifunctional cellular immunity is involved.

High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells in multiple sclerosis patients.

One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system.

A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication.