Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

Abstract

Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain ( Hepatitis C virus (HCV) is an etiologic agent of chronic hepatitis C (1). Chronic HCV infection affects more than 170 million people worldwide and is responsible for approximately 350,000 deaths each year (2). Viral exposure results in acute disease in a small proportion of cases, while the majority (80%) progress to chronic infection, causing liver inflammation that slowly progresses to cirrhosis, liver failure, hepatocellular carcinoma, and death (3).Despite a substantial decline in HCV transmission due to improved prevention strategies and the introduction of new and powerful targeted therapies, hepatitis C remains a huge health problem, justifying further endeavors to develop new vaccines. Indeed, the pool of asymptomatic chronic HCV carriers who represent an infectious reservoir will remain substantial for many years. Less than 30% of patients with chronic hepatitis C are aware of the infection, and only about 10% of patients are currently treated (4, 5). Therefore, even if new antivirals could cure 90% of patients, there would still be a considerable percentage of patients who would be excluded (6). Hence, development of a vaccine to prevent infection or to at least prevent progression to chronicity represents a significant unmet medical need and is of high priority.Since 1% of infected patients show an immune response clearing the infection and the rate of spontaneous resolution is higher in the case of reinfected patients, this demonstrates that the induction of protective immunity which prevents development of chronic disease is a feasible goal for the development of a preventive vaccine against HCV (7,8).The role of HCV-specific T cell responses in the outcome of primary HCV infection has been widely studied, although a single correlate of protection has not been determined. However, it is known that this type of immune response is a determinant in the clearance of the virus. Comparative studies in humans and chimpanzees have shown that widespread and long-lasting CD8 ϩ and CD4 ϩ T cell responses against multiple HCV regions are linked to spontaneous viral clearance (9, 10).However, there is also strong evidence that rapid induction of high-titer cross-neutralizing antibodies targeting HCV envelope proteins correlates with viral clearance and protects against reinfection (11, 12). Therefore, an optimal HCV vaccine probably needs to elicit broad cross-reactive cellular immune responses together with cross-neutralizing antibo...

Bioengineered polyester beads co-displaying protein and carbohydrate-based antigens induce protective immunity against bacterial infection

“…PHB beads were successfully bioengineered to display antigens from intracellular pathogens like Mycobacterium tuberculosis and the Hepatitis C virus. These particulate vaccine candidates elicited both Th1 and Th2 immune responses 26 , 30 , 31 . The elicited immune responses mediated protective immunity against both diseases 26 .…”

Polyhydroxyalkanoate‐associated phasins as phylogenetically heterogeneous, multipurpose proteins

“…Of significant relevance is the implementation of PHAs in the biomedical discipline, especially supported by the recent FDA approval for P(4HB) to be used as suture material (Tepha Inc., MA, USA). The utility of PHAs in this field arises from their biocompatibility characteristics and has found its application in a variety of processes such as drug delivery, development of medical devices and construction of tissue engineering scaffolds (Misra et al ., ; Wu et al ., ; Wang et al ., ; Xiong et al ., ; Brigham and Sinskey, ; Martinez‐Donato et al ., ; Rubio Reyes et al ., ).…”

Bioengineering a bacterial pathogen to assemble its own particulate vaccine capable of inducing cellular immunity

“…Particulate antigen delivery systems are being increasingly considered for vaccine formulations evidenced by recent successful application and commercialization of particle-based vaccines 3 4 . PHA beads had been previously shown to enable delivery of antigens inducing protective immunity in animal models against tuberculosis 5 6 and hepatitis C 7 8 . PHAs are deposited as spherical cytoplasmic inclusions surrounded by proteins 1 9 .…”