October 4, 2022

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New drugs and vaccines for hepatitis B: Restricted surface antigen decline

New drugs and vaccines for hepatitis B: Restricted surface antigen decline

New drugs and vaccines for hepatitis B: Restricted surface antigen decline. Medicinal chemistry is a discipline that requires the spirit of specialized research, and the industry refers to it as a drug researcher. This is a discipline based on chemistry and biology that is applied to the field of new drug development. Xiaofan Health is engaged in the research and development of drugs directly related to medicinalization.

New hepatitis B drugs under research and multiple vaccines are progressing, and the decline of surface antigens is limited. Introduction to the discipline of medicinal chemistry

To put it simply, medicinalization requires in-depth research on the structure and activity of the drug, using the knowledge of chemistry to determine the drug to be developed, and in-depth study of its mechanism of action in the body from the molecular level. The English name of medicinal chemistry is Medicinal chemistry. The research object is drugs, not humans. Simply put, medicinal chemistry is a comprehensive discipline that is responsible for the discovery of new drugs from discovery to synthesis, and elucidating their properties and interactions with body cells. Frontier disciplines.

Where do innovative drugs come from? It is mainly through medicinal chemists designing drug molecules or modifying lead compounds to obtain physical innovative drugs. From the current domestic and foreign direction of new drug development projects, doctors in medicinal chemistry, medical doctors, and chemistry doctors are commonly responsible for the overall development progress of new drugs, including researching drug preparation methods, biology or chemistry, designing new drugs to understand drugs and biology The mechanism of action of the body. Simply put, medicinal chemistry is the development of low-toxicity and high-efficiency drugs that are beneficial to the people.

New drugs and vaccines for hepatitis B: Restricted surface antigen decline 

From the global development of new drugs for chronic hepatitis B, with host innate immunity or adaptive immunity as the target, it has been tracked by pharmacologists for a long time. In theory, this direction is expected to achieve functional cure, but there are also many research drugs that have encountered some development bottlenecks. . A variety of protein/peptide vaccines, live vector vaccines, and DNA vaccines have been popularized in the early stage. We will introduce some new hepatitis B drugs under development based on DNA vaccines that are still in clinical research.

On May 11, 2020, researchers from Morocco, Japan, Bangladesh and other countries published research progress on immune-related targets to achieve functional cures for chronic hepatitis B in the journal Vaccines. The researchers pointed out that INO-1800 is a HBV therapeutic DNA vaccine composed of DNA plasmids encoding hepatitis B surface antigen and hepatitis B core antigen. The drug was developed by Inovio Pharmaceuticals in Pennsylvania, USA, and has been accepted by 90 people. Subjects who have been treated with nucleoside (acid) analogs (NAs) have been evaluated in the Phase 1 clinical trial;

This study evaluates the safety and immunogenicity of the therapeutic DNA vaccines INO-1800 and INO-9112 (DNA plasmids encoding human interleukin-12) dose combination; however, the actual progress of this research is still to be ranked top in the world Published in medical journals (clinical trial number: NCT02431312). HB-100 is another DNA vaccine based on adenovirus. It encodes S1/S2/S envelope gene, polymerase sequence, HBV core and X protein, and uses human IL-12 as an adjuvant.

New drugs and vaccines for hepatitis B: Restricted surface antigen decline

In the Phase 1 clinical study of 12 chronic hepatitis B patients, HB-100 was taken orally with an antiviral drug (adefovir) within 48 weeks; however, the researchers in charge of the trial did not observe significant e-antigen seroconversion . HB-110 is a second-generation adenovirus DNA vaccine with IL-12 as an adjuvant. In the phase 1 clinical trial, 27 patients with chronic hepatitis B were randomized to receive adefovir dipivoxil (ADV) monotherapy or combined with HB-110. According to the researchers, although the HBV-specific T cell response and e-antigen seroconversion of Koreans are weaker than those of Caucasian patients, no adverse reactions were observed after combined treatment with HB-110 and ADV.

  • Among the above several hepatitis B therapeutic vaccines including pre-science popularization, GS-4774 did not achieve a significant reduction in serum hepatitis B surface antigen level in the second phase of the study, and after combined with tenofovir, it did not achieve a significant reduction in surface antigen; NASVAC, The development time is longer, and it can also reduce the level of HBVDNA, and is currently in the process of improvement;
  • DV-601 has been proven to be well tolerated and has antiviral effects in the first phase of the study, and follow-up can be continued;
  • In the first phase of the study, HepTcell showed good tolerance to immunotherapy, but had little effect on hepatitis B surface antigen;

  • TG1050 has proven immunogenicity and antiviral effects in mouse models. In the first phase of human studies, it has shown good safety and induced HBV-specific cellular immunity. Based on the above advantages, it supports its further clinical evaluation (combined medication direction) );
  • In the phase 1 clinical study, AIC649 showed good safety and could reduce the plasma level of IL-10; pCMV-S2.S showed good safety in the clinical study overall, but could not control the recurrence and recovery of anti-HBV immune response ;
  • The dose combination of INO-1800 and INO-9112, and clinical trials evaluating safety and immunogenicity have not yet published research data in medical journals.

 

Conclusion:
The above scientific research data charts and conclusions have been published on Vaccines on May 11, 2020. After the use of HB-100, no significant e antigen seroconversion was observed; the second-generation adenovirus DNA vaccine HB-110 Combined with adefovir dipivoxil in the first phase of human clinical study


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