Designing the global vaccine supply chain: balancing intellectual property rights with post COVID-19 vaccine equity.

This article aims to propose practical solutions that coordinate the conflicting interests between the global community and the pharmaceutical industry on the intellectual property (IP) waiver for COVID-19 vaccines and facilitate a more equitable vaccine supply chain in the post-COVID-19 world. We critically conducted a narrative literature review to identify procedural and practical issues in the current vaccine supply chain. The search was conducted across various academic disciplines, including biomedical science, life science, law and social science, using resources such as PubMed, Web of Science, Scopus and Westlaw. After screening 731 articles, 55 studies were selected for review. The narrative review revealed several critical barriers that hinder vaccine supply in less-developed countries (LDCs) as follows: (1) WTO Trade-Related Aspects of Intellectual Property Rights (TRIPs) waiver requests may not be granted due to its stringent consensus rule; (2) the current compulsory license system may not work due to the complexity of IP rights covering COVID-19 vaccine technologies; (3) only a few LDCs have domestic companies capable of manufacturing vaccines, and (4) political and economic tensions among countries exacerbate existing barriers to vaccine distribution in LDCs. Based on these findings, we proposed a comprehensive compulsory license system, which combines TRIPS's compulsory license system with the third-party beneficiary mechanism under Common Law. This integrated approach offers a balanced solution that ensures fair compensation for vaccine developers while facilitating broader vaccine access.

Structural characterization of the α-mating factor prepro-peptide for secretion of recombinant proteins in Pichia pastoris.

The methylotrophic yeast Pichia pastoris has been used extensively for expressing recombinant proteins because it combines the ease of genetic manipulation, the ability to provide complex posttranslational modifications and the capacity for efficient protein secretion. The most successful and commonly used secretion signal leader in Pichia pastoris has been the alpha mating factor (MATα) prepro secretion signal. However, limitations exist as some proteins cannot be secreted efficiently, leading to strategies to enhance secretion efficiency by modifying the secretion signal leader. Based on a Jpred secondary structure prediction and knob-socket modeling of tertiary structure, numerous deletions and duplications of the MATα prepro leader were engineered to evaluate the correlation between predicted secondary structure and the secretion level of the reporters horseradish peroxidase (HRP) and Candida antarctica lipase B. In addition, circular dichroism analyses were completed for the wild type and several mutant pro-peptides to evaluate actual differences in secondary structure. The results lead to a new model of MATα pro-peptide signal leader, which suggests that the N and C-termini of MATα pro-peptide need to be presented in a specific orientation for proper interaction with the cellular secretion machinery and for efficient protein secretion.