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OP225
Pharmacological development of HeberNasvac, a novel
therapeutic vaccine against chronic hepatitis B
Gerardo enrique Guillen Nieto1,2, Yadira Lobaina2, Maryline
Bourgine3, Marie Louise Michel4, Freya Freire2, Julio cesar
Aguilar2,5
1Research Director, Trieste, Italy; 2Center for Genetic Engineering
and Biotechnology, Trieste, Italy; 3Institut Pasteur, Paris, France;
4Institut Pasteur, Paris, France; 5Project Leader, Paris, France
Background: Despite the existence of effective prophylactic vaccines,
hepatitis B virus (HBV) infections remain a major public health
problem. About 370 million people are chronically infected worldwide.
Chronic hepatitis b (CHB) infection also increases the risk of
liver diseases such as cirrhosis and hepatocellular carcinoma.
Current antiviral therapies fail to control viral replication in the long
term in most patients. As HBV persistence has been associated with a
defect in the development of HBV-specific cellular immunity,
immuno-therapeutic approach as therapeutic vaccination could contribute
to break the tolerance, to the long term control of viral DNA
and to increase the seroconversion rates against HBeAg and HBsAg.
The development of therapeutic vaccines against CHB requires
proofing the capacity of the formulation to induce broad humoral and
cellular immunological response.
Methods: NASVAC as a new generation vaccine include the use of a
novel immunization route (intranasal-IN) and a novel antigen
(HBcAg) expressed in E. coli, used in a combined formulation with
HBsAg extressed in Pichia pastoris, both as VLPs. The formulation is
a simple mixture of proteins in phosphate buffer administered by the
IN and SC routes. The immunogenecity in Balb/C and transgenic
mice was measured using ELISA, LPA and IFN-g ELISPOT assays.
The pharmacological studies where approved by the Ethical Committees
on Animal Research.
Result: The evaluation in mice and early clinical development support
the rationality of the dose and formulation as well as the
administration routes. The therapeutic vaccine candidate targeted the
stimulation of CD4(+) and CD8(+) T-cell responses and the induction
of pro-inflammatory cytokines capable of controlling viral replication.
HeberNasvac proved to be immunogenic in mouse models and in
clinical trials in humans.
Hepatol Int (2017) 11 (Suppl 1):S1–S1093 S149
Conclusion: Pharmacological results with HeberNasvac evidenced
the vaccine immunogenicity and supported the vaccine formulation
and administration routes.
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发表于 2017-2-11 22:52
