Traditional vaccine is antigen-based vaccine, but mutated antigen can fail the previous vaccination. Therefore, production of non-antigen-based or altered- gene-expression-based cure-all vaccine could be a major breakthrough in vaccine development. Plasmodium sporozoites invade hepatocytes via infected female Anopheles mosquito bite and the sporozoites mature and multiply into thousands of merozoites inside cells, which is quite like viral infection and as such, the antiviral theory I proposed in 2020 could be used to explain the reason why the sporozoites can specifically invade hepatocytes and consequently, changing gene expression patterns randomly in hepatocytes by non-carcinogenic genotoxic drugs (NCGDs) could prevent all malaria infections. If one dose of NCGD treatment can cause long duration of action, the treatment could be a NCGD-induced cure-all vaccine for prevent all malaria infections. Recently, N- acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) can prevent rodent and Plasmodium falciparum infections and its pharmacodynamics are long duration of action for silencing the target gene with quarterly or bi-annual dosing regimens in human, which indicates that GalNAc-conjugated siRNA treatment is a special vaccine for malaria prevention. Since GalNAc-conjugated siRNA might belong to NCGDs, it is possible that GalNAc-conjugated siRNA could alter gene expression patterns in hepatocytes. Therefore, the special vaccine produced by GalNAc-conjugated siRNA might be a NCGD-induced non-antigen-based or altered-gene-expression-based cure-all vaccine for preventing infections of all five types of human plasmodium species and hepatitis viruses without causing drug resistance in the pathogens. Furthermore, this approach could be used to make non-antigen-based or altered-gene-expression-based cure-all vaccine for preventing all viral infections, indicating that the antiviral theory I proposed in 2020 could also be a theory for making non-antigen-based or altered-gene-expression-based cure-all vaccine for preventing all plasmodium and viral infections. The successful achievement for cure-all vaccine production could mark a historic advance in vaccine development.



