Development of hepatitis B protein/peptide or live carrier
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DeDevelopment of hepatitis B protein/peptide or live carrier, generally well tolerated, short-term weak reaction becomes difficult
Development of hepatitis B protein/peptide or live carrier, generally well tolerated, short-term weak reaction becomes difficult. At the recent American Liver Disease Research Conference 2020 (AASLD2020), Japanese researchers introduced the latest progress of a therapeutic candidate vaccine NASVAC. The development of this candidate vaccine is actually a twists and turns. Judging from the available registration information, The earliest human phase 1 clinical study of this candidate vaccine has started in May 2011 (see the figure below).
Development of hepatitis B protein/peptide or live carrier, generally well tolerated, short-term weak reaction becomes difficult
Xiaofan Health also introduced in the previous period that NASVAC is a therapeutic candidate vaccine containing both hepatitis B surface antigen and core antigen. In an open, phase III, randomized, treatment-controlled clinical trial, NASVAC is lower than Peg-IFN treatment. The level of serum hepatitis B virus DNA. Around May 2020, a Tupaia model study showed that intranasal immunity formulated with HBs-S or HBs-L and HBc combined with carboxyvinyl polymer (CVP) can induce strong IgG, IgA, Neutralizing antibody and HBV protein specific IFN-γ immune response.
In addition to the candidate vaccine NASVAC, DV-601 is a therapeutic vaccine composed of HBs and HBc antigens. In its phase 1 study, it was found to be safe and well tolerated, and produced an antiviral response. HepTcell, which is an immunotherapeutic synthetic research drug, consists of 9 peptides (from 3 different HBV antigens (polymerase, core and surface) highly conserved regions) designed to stimulate CD4+CD8 in HBV carriers +T cells, regardless of their HLA background.
In its phase 1 clinical study, HepTcell immunotherapy with IC31 (TLR9 agonist) adjuvant was found to be well tolerated and increased the T cell response to HBV, but not to hepatitis B surface antigen. influences. The above-mentioned several, plus the previous popular science GS-4774, are all protein/peptide vaccines. There is also a live vector vaccine TG1050 globally, which can be analyzed separately for its mechanism of action and test progress.
TG1050, which is a therapeutic vaccine based on adenovirus, expresses 3 kinds of HBV protein (polymerase, core and surface antigen), and shows (preclinical animal model) immunogenicity and antiviral effect in mice. In the Phase 1 clinical trial of chronic hepatitis B treated with nucleoside drugs (NA), TG1050 showed good safety and induced HBV-specific cellular immunity, supporting its further clinical evaluation, especially in combination therapy.
Another live vector vaccine is AIC649. Its phase 1 clinical trial found that this is an inactivated parapox virus (iPPVO) preparation, which is well tolerated and can increase IL-1β, IL-6, and IL. -8 and IFN-γ levels, while reducing IL-10 plasma levels. In the early 1990s, there was the first report in the world that plasmid DNA induces an immune response to plasmid-encoded antigens. Therefore, DNA vaccines have gradually become a new type of immunization method and a rapidly developing field of vaccine technology.
Compared with the short half-life of injected protein antigen, plasmid DNA can provide tissue expression of the antigen in a longer period of time, so it may better activate the immune system. pCMV-S2.S is a DNA vaccine that encodes HBV small (S) and medium (pre2+S) envelope proteins. Moroccan and Japanese researchers published a related introduction in Vaccines on May 11, 2020. In the Phase 1 clinical trial of 10 chronic HBV carriers, it was well tolerated and was able to activate or restore T cell responses in some chronic hepatitis B carriers; however, this effect was short-lived and weak.
The efficacy of pCMV-S2.S-DNA in preventing the recurrence of hepatitis B virus was subsequently studied in a phase 1/2 clinical trial of 70 patients who received effective treatment with nucleoside drugs. Although the research results show that pCMV-S2.S is safe, it cannot control the recurrence and recovery of the anti-HBV immune response. Therefore, it can be seen that so far, modern science has made considerable progress, but whether it is in the direction of protein/peptide vaccines, or in the direction of live vector vaccines and DNA vaccines, they have encountered considerable resistance. This is also a scientific research point of view. Back to the opening candidates The development time span of the vaccine NASVAC (protein/peptide vaccine) is too long, which is mainly based on the above reasons (difficulties and progress have been described in detail in the content, leaving scientists a little more time and more understanding
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