Hepatitis C virus (HCV) infection is a worldwide health problem. Vaccines against this pathogen are not available and advances in this field are limited because of the high genetic variability of the virus, inaccessibility of animal models, and incomplete definition of immunological correlates of protection. In the present work, a chimeric protein, Eq1, encompassing HCV amino acid regions from structural antigens, was generated. Eq1 was expressed in GC-366 bacterial cells. After cell disruption, Eq1 was purified from the insoluble fraction by sequential steps of differential solubilization and metal chelating affinity chromatography. Eq1 was specifically recognized by anti-HCV positive human sera. Moreover, immunization of BALB/c mice with different doses of Eq1 formulated either in Alum or Freund's incomplete adjuvant elicited both humoral- and cellular-specific immune responses. Doses of 20 µg of Eq1 induced the strongest cell-mediated immune responses and only the formulation of this dose in Alum elicited a neutralizing antibody response against heterologous cell culture HCV. All these data together indicate that Eq1 is immunogenic in mice and might be an interesting component of vaccine candidates against HCV infection.
Apoptosis was initially seen as a kind of silent cell death with non-induction of the immune response 1. However, in the recent past, it has been seen that death induced by either infections or actions of certain agents can elicit a specific immune response, namely immunogenic cell death (ICD)2. This ICD activates the immune system against antigens associated with deceased cells with the concomitant exposure and releasing of the so-called damage-associated molecular patterns (DAMPs) by dying cells3. Four principal DAMPs related to ICD have been identified (but not limited to): the endoplasmic reticulum (ER) chaperone calreticulin (CRT), heat shock proteins (HSPs), adenosine triphosphate (ATP) and high mobility group box-1 (HMGB-1)4.
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