Neutralizing antibodies and broad, functional T cell immune response following immunization with hepatitis C virus proteins-based vaccine formulation

Martínez‐Donato, Gillian; Amador-Cañizares, Yalena; Alvarez‐Lajonchere, Liz; Guerra, Ignacio Ruiz; Pérez, Ángel; Dubuisson, Jean; Wychowsk, Czeslaw; Musacchio, Andrea; Aguilar, Daylen; Dueñas‐Carrera, Santiago

doi:10.1016/j.vaccine.2014.01.046

Cited by 12 publications

(19 citation statements)

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“…In order to assess a formulation able to induce an immune response targeting a variety of HCV epitopes, an immunization schedule with Beads-Core mixed with recombinant HCV E1, E2, and NS3 proteins (Beads-CoreϩE1E2NS3/ Alum) was carried out in mice. In this experiment, we compared the specific immune responses induced by three doses of a vaccination regimen of Beads-CoreϩE1E2NS3/Alum to those induced by five doses of a mix of HCV recombinant proteins Core, E1, E2, and NS3 formulated in Alum (CoE1E2NS3/Alum) (15). Mice injected with Alum and control Beads/Alum were used as negative controls.…”

Section: Resultsmentioning

confidence: 99%

“…For example, classical and nonclassical ISCOMs have been shown to prime CD4 ϩ -and CD8 ϩ -mediated immune responses and memory cellular immune responses (48,49). Recently, we demonstrated that Core-VLP immunization coadministered with E1, E2, and NS3 proteins induced broad T cell proliferation and IFN-␥ responses in mice and monkeys (15). Accordingly, the nature of antigens and the association between antigen and adjuvant are thought to be crucial for induction of functional T cell immune responses (50).…”

Section: Discussionmentioning

confidence: 99%

“…Since Core and NS3 antigens comprise the most relevant epitopes related to the cell-mediated immune response against HCV (9,57) and the viral E1 and E2 glycoproteins contain epitopes inducing neutralizing antibody responses found to be protective (58) and associated with the resolution of hepatitis C infection (59), Beads-Core was coadministered with recombinant E1.340, E2.680, and NS3 proteins. It had been demonstrated that CoE1E2NS3 (MixprotHC) vaccination induces broad HCV-specific humoral and cellular immune responses after immunization with five doses in mice and monkeys (15,37). A MixprotHC formulation previously showed induction of cross-neutralizing antibodies in mice and African green monkeys, and the specific T cell-induced immunity provided protection in a surrogate vaccinia virus-HCV challenge model (15).…”

Section: Discussionmentioning

confidence: 99%

“…injections into the quadriceps muscle of CoE1E2NS3/Alum (a mixture of 0.1 g Co.120, 16.7 g E1.340, 16.7 g E2.680, and 10 g NS3 adjuvanted in alum) as described before (15) or Beads-CoreϩE1E2NS3/Alum (Beads-Core mixed with 16.7 g E1.340, 16.7 g E2.680, 10 g NS3, and alum). Animals injected with alum or beads without antigen in alum (Beads/Alum) were used as negative controls.…”

Section: Methodsmentioning

confidence: 99%

“…Several immunization approaches have been evaluated against HCV (13)(14)(15)(16). These studies showed that selection of appropriate adjuvants and appropriate presentation of the proteins are critical elements in vaccine development.…”

mentioning

confidence: 99%

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

Martínez‐Donato

Piniella

Aguilar

et al. 2016

Clin Vaccine Immunol

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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...

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Section: Resultsmentioning

confidence: 99%