Enhanced T Cell Responses Induced by a Necrotic Dendritic Cell Vaccine, Expressing HCV NS3

Abstract

A vaccine that induces potent, broad and sustained cell-mediated immunity, resulting in effective memory has the potential to restrict hepatitis C (HCV) virus infection. Early, multi-functional CD4+ and CD8+ T cell responses against non-structural protein 3 (NS3) have been associated with HCV clearance. Necrotic cells generate strong immune responses and represent a major antigenic source used by dendritic cells (DC) for processing and presentation, but there is conflicting evidence as to their immunogenicity in vaccination. Immunization with DC loaded with viral antigens has been done in the past, but to date the immunogenicity of live vs. necrotic DC vaccines has not been investigated. We developed a DC2.4 cell line stably expressing HCV NS3, and compared the NS3-specific responses of live vs. necrotic NS3 DC. Vaccination of mice with necrotic NS3 DC increased the breadth of T-cell responses and enhanced the production of IL-2, TNF-α, and IFN-γ by effector memory CD4+ and CD8+T cells, compared to mice vaccinated with live NS3 DC. A single dose of necrotic NS3 DC vaccine induced a greater influx and activation of cross-presenting CD11c+ CD8α+ DC and necrosis-sensing Clec9A+ DC in the draining lymph nodes. Furthermore, using a hydrodynamic challenge model necrotic NS3 DC vaccination resulted in enhanced clearance of NS3-positive hepatocytes from the livers of vaccinated mice. Taken together, the data demonstrate that necrotic DC represent a novel and exciting vaccination strategy capable of inducing broad and multifunctional T cell memory.

Modern antiviral biomedical cell products and their applications for COVID-19 therapy

“…Кроме того, проводятся исследования по созданию ДК-вакцин против вируса гепатита С (ВГС) [35][36][37]. B. Hong и соавт.…”

“…A. Mekonnen и соавт. разработали другой подход для повышения эффективности ДК-вакцины против ВГС [37]. Они предполагают использовать некротические ДК, экспрессирующие антиген ВГС для иммунизации.…”

Glyceraldehyde-3-phosphate Dehydrogenase Common Peptides of Listeria monocytogenes, Mycobacterium marinum and Streptococcus pneumoniae as Universal Vaccines

“…Dendritic cells (DC) are efficient experimental vaccine vectors as they can stimulate CD8 + and CD4 + T cells and induce Th1 cytokine profiles, relevant features of efficient vaccines for infectious diseases. In this regard, DC vaccines have been proposed against different viral and bacterial infections such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), type 2 coronavirus (SARS-CoV2), Streptococcus pneumonia, Chlamydia trachomatis , Mycobacterium tuberculosis and Listeria monocytogenes [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”