RSV

Respiratory syncytial virus vaccine: vast blue ocean market

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The burden of the disease is concentrated in immunocompromised individuals, lacking specific prevention and treatment methods, which has caused great clinical burden and social harm

RSV infection is epidemic among children under 5 years old, the elderly over 65 years old, and immunocompromised individuals. It causes tens of millions of infections and tens of thousands of deaths every year, resulting in a serious burden of disease.

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Respiratory syncytial virus (RSV) is a worldwide epidemic virus and cause serious social burden. In decades, research results shown that the prefusion structure of the RSV F glycoprotein has more epitopes compared with postfusion RSV F.

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Structure-based design of prefusion-stabilized RSV-F protein

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The identification of Pre-F structure as the main target of neutralizing antibodies is important for the development of RSV vaccine.

How to get the stability prefusion structure of the RSV F glycoprotein is a global problem.

Struture-based design of antigen is a new direction in drug innovation. In this part, the structure of RSV-preF was used as the template to generate the new proteins. The new structures retain the epitopes of RSV-preF and precise induce the RSV-neutralizing antibodies

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AI design flow of RSV-PreF. The new structure immunogenicity was measured by neutralizing antibody titer.

The choice of relative element in RSV vaccine development

Transportation and preservation of vaccines is a key element of access to vaccines. Almost all of vaccines need to be stored at -20 °C due to their poor stability. The burden of RSV spread is concentrated in developing countries where can not provide qualified storage conditions. Therefore, the freeze-dry maybe an appropriate choice. The results shown that forms of freeze-dry is useful to enhance neutralizing antibody due to higher stability compared with liquid. We also assessed other elements compared with commercial product. As shown in the neutralizing antibody titer, Rh-LNP-IE and RhCap induced more immune effect compared with SM102 and Cap1.

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Immune effect of different antigens with different elements.

Table: antigenic information of immunoevaluation

Group Positive RH112 RH112(Cap1) RH112(SM102) RH112(freeze-dry)
Numbers 10 10 10 10 10
LNP SM102 Rh-LNP-IE Rh-LNP-IE SM102 Rh-LNP-IE
Cap Cap1 RhCap Cap1 RhCap RhCap
Dose 5ug 5ug 5ug 5ug 5ug
Forms of drug liquid liquid liquid liquid Freeze-dry

Process development

Process development work is often carried out after the end of pre-research and before the official production. The pre-research work in the early stage of RSV project shows that the candidates have good feasibility in preclinical experiments. Therefore, it is necessary to develop relevant processes suitable for future large-scale production for the purpose of efficiency, stability and economy. Through small-scale process development and confirmation to realize purpose of higher yield, purity and economy.

RSV uses the company's mature process platform to coordinate the adaptability between the self-designed sequence and the self-developed components. Optimize the process flow and simplify it.

The purity of plasmid template reaches more than 99%, and the endotoxin is less than 0.08EU/μg.

In terms of stock solution, the double-stranded residual is far less than 0.04μg/mg, and the capping rate is more than 97%

The encapsulation rate of the freeze-dried product is more than 95%.

Scale production

Stable and efficient process development is the prerequisite for large-scale production expansion, while production environment in compliance with laws and regulations is the key to ensuring drug declaration and listing. The company strictly follows GMP regulations in material management, institutional management, environmental management, equipment management, and quality management.

Rigorous production management ensures the integrated production of the whole RSV process, and ensures the basic principles of "safe, effective and controllable quality" for drug development. The independent platform capacity can meet the extreme requirement of completing a batch of production within 30 days.

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Quality Control

The pharmaceutical quality system is a management system established to guide pharmaceutical companies in controlling the quality of drugs in terms of quality. It manages all factors that affect product quality throughout the entire product lifecycle.

In the RSV project production, quality control, quality research, and strict release testing are conducted on plasmids, bulk solutions, and semi-finished products. This ensures that the production process and product quality meet standards, and batch comparability is achieved.