RESUMO
The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants following an order of BA.1>BA.2>BA.4/5. In naive animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccines targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection across all VOCs. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine- primed populations.
RESUMO
A major hurdle that humbles the modernization of traditional Chinese herbal medicine (CHM) is the inconsistency of chemical composition, which is inevitable due to the natural origins of CHM. Here I propose a concept of a new category of drugs, named "post-absorption/metabolism multicompound drug (PAMD)" that will meet every standard of modern pharmaceuticals, yet maintain the fundamental principle of traditional Chinese medicine, which is an integrative therapeutic approach through multiple mechanisms by a cocktail of various herbs. The PAMD concept is based on the fact that the most of chemical ingredients in an orally taken CHM remedy may never enter the blood stream owing to the poor gastrointestinal absorption. Only a few original ingredients or, most likely, a few metabolites of those absorbed ingredients are found in the blood or target organs. The compounds after the absorption/metabolic process are the only ones responsible for pharmacological functions of the remedy. Given the limited number of species, those compounds, once isolated and tested for their pharmacological activity, can be formulated with designed ratios to form new drugs that should theoretically possess an equivalent or better therapeutic efficacy than the original CHM remedy. Strategies of developing PAMDs and possible difficulties are also discussed.
