Nanotechnology-based mRNA vaccines: From the fight against COVID-19 to cancer immunotherapy and HIV vaccines

(Nanowerk Spotlight) COVID-19 is a game changer for both nanomedicine and nucleic acid-based vaccines. Just two years ago, there were no licensed messenger RNA (mRNA) vaccines; today Pfizer-BioNTech and Moderna mRNA vaccines are among the approved vaccines for protection against COVID-19. More than one billion doses of mRNA-based COVID-19 vaccines have been administered around the world as the first line defense against COVID-19.
Regardless of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) keeping mutating, and causing a new variants, nanotechnology-based mRNA vaccines remain the most effective and safe vaccines to defend against COVID-19 for adults and children, from ages 6 months and older.
To evoke protective immunity against the coronavirus, COVID-19 mRNA vaccines use a mRNA code for a protein found on the surface of the SARS-CoV-2 virus. Once the mRNA enters host cells, it instructs them to make spike proteins and stimulate the immune system to make antibodies against SARS-CoV-2.
Since it is very difficult for the fragile genetic material to enter a host cell on their own, they are encapsulated with lipid nanoparticles (LNP) to help the mRNA molecules get into the cells. Without these lipid shells, there would be no mRNA vaccines for COVID-19.
In essence, nanotechnology offers solutions to overcome the unmet delivery challenges associated with the use of naked mRNA for the vaccine developer. Lipid and polymeric nanoparticles are among the examples of nanocarriers used to safely deliver mRNA into a host cell targeted through an endosome.
The rapid development of COVID-19 mRNA vaccines would not have been feasible without the advancement of LNP technology. LNP used in the COVID-19 vaccines consists of four ingredients: 1) cationic or ionizable lipids to improve the entrapment of mRNA; 2) pegylated lipids help to prevent particle aggregation, prolong circulation lifetimes and evade the immune system; 3) phospholipids; and 4) cholesterol molecules contribute towards the stability of lipid bilayer structure.
The advantages of nanotechnology-based mRNA vaccines are that they are easy to design, easy to manufacture and can be scaled up in larger volume, which offer advantages over traditional vaccines (e.g., inactivated, and live-attenuated strains) that still require cultures and are very expensive. In addition, nanoparticles can attach to the virus and disrupt its structure, making it difficult for the virus to survive and reproduce in the body.
The success of mRNA technology in the development of a COVID-19 vaccine has become a groundbreaking development in the fight against cancer, as well as in the development of new vaccines against many other infectious diseases, including HIV.

Cancer immunotherapy

Cancer immunotherapy is a form of cancer treatment that uses the body's own immune system to combat and/or eliminate cancer. Over the past few years, research focusing on the use of mRNA vaccines for cancer immunotherapy has become an innovative ground for combating cancer, such as brain, breast, melanoma, lung, ovarian, prostate cancer, and solid tumors.
Some of these mRNA vaccines have already passed vaccine development Phase I and Phase II, and are now in phase III clinical trials. mRNA-4157 (a personalized mRNA vaccine developed by Moderna) is an example of a mRNA vaccine for melanoma that has completed Phase I and is currently undergoing Phase II clinical trials.
Another example is the mRNA vaccine BNT112 developed by BioNTech to treat metastatic prostate cancer has entered Phase II clinical trials.
DEN-STEM is an example of a dendritic cell transfected with mRNA from autologous tumor stem cells, survivin and hTER for cancer stem cells for glioblastoma and is currently undergoing Phase III clinical trials.

HIV mRNA vaccines

Recently, the non-profit scientific research organization, International AIDS Vaccine Initiative (IAVI), and Moderna announced their joint venture towards screening for a Phase I clinical trial of a mRNA HIV vaccine antigen (eOD-GT8 60mer mRNA vaccine, mRNA-1644) at the Centre for Family Health Research (CFHR) in Kigali, Rwanda, and The Aurum Institute in Tembisa, South Africa. A Phase I study aims to evaluate the safety and immunogenicity of mRNA-1644 (eOD-GT8 60mer) in HIV-1 uninfected adults.
The eOD-GT8 60mer immunogen is a germline-targeting antigen that can stimulate neutralizing antibodies to many different genetic variants of HIV without causing HIV infection. The mRNA-1644 (eOD-GT8 60mer) vaccine utilizes Moderna's mRNA vaccine technology to safely deliver germline-targeting antigen to target cells.

The future of nanotechnology-based mRNA vaccines

Future nanotechnology-based mRNA vaccines could allow the delivery of multiple antigen-targeted vaccines in one vaccine lipid nanoparticle to protect against multiple diseases, thereby reducing the number of vaccines needed to prevent common vaccine-preventable diseases.
We are also likely to see nanotechnology being used to reformulate old vaccines as well as no longer used medicines and their return to clinics and hospitals.
The convergence of nanomedicine with other technologies in the fourth industrial revolution (such as artificial intelligence, robotics, and 3D printing) has the potential to revolutionize medicine and make it easier to treat complex diseases such as heart disease, diabetes, and cancer.
By Dr Steven Mufamadi, Research Chair in nanomedicine of the DSI-Mandela Nanomedicine Platform of Nelson Mandela University, and the founder of Nabio Consulting (Pty) Ltd. He holds a PhD in Pharmaceutics from the University of the Witwatersrand, Johannesburg, South Africa. Dr Mufamadi has received training in pharmaceutical nanotechnology from Novartis Pharma in Basel, Switzerland. He was a finalist for 2019/2020 NSTF South 32 Awards in the category: Communication award in 2020; and a winner in the bio-communicator category at the Gauteng Biotech Fundi awards in 2017.

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