The technology for the production of vaccines has taken a new turn towards DNA vaccines, which are proving to be highly effective and the future of therapeutics against cancers and chronic infections. As compared to the live attenuated early vaccines and the subunit vaccines, DNA vaccines are found to provide increased immunity with a better safety profile. One or more sequences of antigen are encoded by p-DNA (plasmid DNA) that can result in the lasting and enduring expression of antigen within the cell, triggering vigorous immunization responses along with a sturdy humoral immunity. The first DNA vaccine of HIV marked a period of a large number of researches in the area but the FDA has still not allowed testing the vaccines for humans for more than a couple of decades. In this regard, the most typical challenge faced by the researchers is the poor ability of gene transfection causing low immunogenicity in body.
Several physiological hurdles hinder the effective transfer of p-DNA into the nucleus of the cell for transfection which becomes a limiting factor in the efficient performance of DNA vaccine in vivo. Therefore, appropriate gene vectors are needed for protecting and transporting the DNA molecules to gain elevated antigen expression, and also play a role of adjuvant for high immune responses. The system of gene delivery with nanoparticles has attracted a large amount of research in this aspect. Various nano-materials both organic and inorganic have shown promising results in vitro but few excel in vivo.
To this note, researchers from the University of Queensland in Australia, Professor Chenzhong Yu and Dr. Hao Song, used rationally designed MSNs (mesoporous silica nanoparticles) as nano-vectors for DNA vaccine delivery in vivo. The researchers proposed that Ram-MSNs (abbreviated for “rambutan-like mesoporous silica nanoparticles”) featured with a unique spiky nanotopogarphy can act as favorable nano-vectors to capture and protect the p-DNA molecules. They presented the initial example of DNA vaccines that utilize Ram-MSNs for delivering pDNA-OVA (pDNA encoded by ovalbumin) in vivo. The research is now published in the journal of Advanced Therapeutics.
The research team observed that utilizing Ram-MSNs as both adjuvants and gene vectors elevated antibody production and increased maturation of antigen presenting cells resulting in higher immunity response. When they tested their formulation (vaccine utilizing Ram-MSNs) in mice, it specifically showed amplified IgG antibody that was antigen-specific, increased production for IFN-γ cytokine and boosted T-cells CD8+. Based on the immune responses of Ram-MSN-based DNA vaccines, the researchers clearly noticed that their developed Ram-MSN vaccines surpassed the agents used in the transfection commercially (in vivo-jetPEI).
Indeed, Professor Chengzhong Yu and his research team provided great evidence of exceptional immune responses through DNA vaccines with nanoparticles. This DNA vaccine technology has been patented and licensed to N4 Pharma, a UK-based pharmaceutical company, toward the clinical translation for the prevention and treatment of infection and chronic diseases. With the COVID-19 virus pandemic and the race to develop a vaccine to stop the disease, this research is timely and provide a new tool for future design and development of vaccines.
Song, H., Yang, Y., Tang, J., Gu, Z., Wang, Y., Zhang, M., Yu, C. DNA Vaccine Mediated by Rambutan-Like Mesoporous Silica Nanoparticles, Advanced Therapeutics (2020) 3, 1900154, DOI: 10.1002/adtp.201900154Go To Advanced Therapeutics