Abstract
Chronic hepatitis B (CHB) is the cause of severe liver damage, cirrhosis, and hepatocellular carcinoma for over 240 million people worldwide. Nowadays, several types of treatment are being investigated, including immunotherapy using hepatitis B core antigen (HBcAg) assembled into highly immunogenic capsid-like particles (CLPs). Immunogenicity of plant-produced and purified HBcAg, administered parenterally or intranasally, was previously reported. In this study, a novel parenteral–oral vaccination scheme is proposed using plant-derived HBcAg preparations. The antigen for injection was obtained via transient expression in Nicotiana benthamiana. HBcAg-producing transgenic lettuce was lyophilized and used as an orally delivered booster. The intracellular location of plant-produced HBcAg CLPs implies additional protection in the digestive tract during oral immunization. BALB/c mice were intramuscularly primed with 10 µg of the purified antigen and orally boosted twice with 5 or 200 ng of HBcAg. A long-lasting and significant systemic response after boosting with 200 ng HBcAg was induced, with anti-HBc titer of 25,000. Concomitantly, an insignificant mucosal response was observed, with an S-IgA titer of only 500. The profile of IgG isotypes indicates a predominant Th1 type of immune response, supplemented by Th2, after injection–oral vaccination. The results demonstrate that a low dose of parenteral–oral immunization with plant-derived HBcAg can elicit a specific and efficient response. This study presents a potential new pathway of CHB treatment.
Highlights
Hepatitis B virus (HBV) still remains the major cause of liver diseases, especially in developing countries [1]
Vacuum-assisted infiltration resulted in a lower hepatitis B core antigen (HBcAg) content, approximately 0.2 mg/g of fresh weight (FW) in comparison to 0.6–1 mg/g FW for syringe-based infiltration
There were no significant differences in HBcAg accumulation after infiltration with the two Agrobacterium strains (Figure 1a)
Summary
Hepatitis B virus (HBV) still remains the major cause of liver diseases, especially in developing countries [1]. Because of problems with the management of HBV infection, emergence of HBV mutants and considerable extent of non-responsiveness to vaccines, an estimated over 2 billion people suffer from hepatitis B. 10%–15%, especially infants, remain chronically infected, which is one of the causes of the Vaccines 2019, 7, 211; doi:10.3390/vaccines7040211 www.mdpi.com/journal/vaccines. Vaccines 2019, 7, 211 maintained reservoir of the virus [1,2]. Chronic hepatitis B (CHB) is a type of HBV infection, where the presence of the virus persists for more than six months and may extend to produce a life-long disease. Persistent infection may disrupt physiological functions of the liver. It is estimated that at least 240 million people are living with
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