Vaccination has been the most successful medical strategy in the past century to lower death and morbidity rates from infectious diseases. Worldwide, immunizations are thought to save between two and three million lives annually.
mRNA vaccines are emerging as a viable and effective substitute for conventional vaccines due to their various desirable characteristics. They make excellent candidates for the prevention and treatment of infectious diseases, particularly during pandemics, due to their ease of production, low cost, safety profile, and great potency. mRNA vaccines instruct the body's cells to generate a protein that elicits an immune response by using a synthetic form of messenger RNA (mRNA). mRNA vaccines depend on the genetic instructions for generating a particular antigen, in contrast to conventional vaccines, which frequently use weakened or inactivated viruses.
mRNA Vaccines Against SARS-CoV-2
The fight against SARS-CoV-2, the virus that causes COVID-19, has benefited greatly from mRNA vaccines. These vaccinations have had a major influence on public health worldwide and were the first mRNA-based medicines to be widely approved. The fastest vaccination to be created was Pfizer's COVID-19 vaccine, which was approved for emergency use by the FDA in December 2020, just over seven months after its phase I/II study concluded in May 2020. Both Pfizer and Moderna vaccines have a similar mechanism of action.
The vaccine, which is administered in lipid nanoparticles for improved host cell delivery, contains a nucleoside-modified mRNA that codes for the SARS-CoV-2 spike glycoprotein. The mRNA encodes for the S2-P antigen, which is made up of the transmembrane-anchored SARS-CoV-2 glycoprotein. To assess efficacy, binding antibody reactions against S2-P were employed. The purpose of the vaccination is to trigger T-cell and B-cell reactions to the spike protein. The vaccine effectively produced antibody responses to both the receptor-binding domain and full-length S2-P, according to published data.
Potential of mRNA Vaccines in Treating Cancer
A range of cancer diagnoses and delivery methods have been used to evaluate the immunogenicity and therapeutic efficacy of mRNA vaccines. During vaccination, antigen-presenting cell (APC) activation and innate/adaptive immune stimulation are facilitated by naked or vehicle-loaded mRNA vaccines, which effectively express tumor antigens in APCs.
Following mRNA-based vaccination treatment, a small number of trials have documented long-lasting objective responses in cancer patients without uncontrollable harmful side effects. However, a few limitations, such as innate immunogenicity, instability, and ineffective in vivo administration, have restricted the use of mRNA vaccines. To address these issues, appropriate mRNA structure modifications, such as codon optimizations, nucleotide alterations, self-amplifying mRNAs, etc., and formulation techniques, such as lipid nanoparticles (LNPs), polymers, peptides, etc., have been studied. Broadly, mRNA vaccines show promise as therapeutic possibilities for cancer treatments in the future, particularly when used in conjunction with other immunotherapies.
Advantages of mRNA Vaccines Over Conventional Vaccines
mRNA-based vaccinations have gained international attention because of the COVID-19 pandemic. They also have various advantages over conventional vaccines, such as being non-infectious since no pathogenic viral agent is used. mRNA-based vaccines are readily broken down, well-tolerated, and are not integrated into the host genome, which prevents the threat of insertional mutagenesis. Also, mRNA vaccines can elicit both humoral and cell-mediated immunity.
The side effects of mRNA vaccines are transient and easily manageable. In addition, mRNA vaccines are more effective and have a better safety profile than viral vector and DNA vaccines because they can be translated into the desired gene as soon as they enter the cytoplasm of the cell rather than needing to go to the nucleus. Two of the most beneficial advantages of mRNA vaccines are that these vaccines can be produced quickly and are cost-effective. Pfizer-BioNTech’s COVID-19 vaccine (Comirnaty), along with Moderna’s Spikevax, holds the record for the fastest vaccine development in history, and both are mRNA-based vaccines.
Future of mRNA Vaccines
Numerous mRNA vaccines against different pathogens are already under development, as are mRNA-encoding antibodies for passive vaccination to cure or prevent a range of infectious disorders. Clinical trials are also being conducted to restore vascular malfunction in the heart or diabetic wounds and to fight cancer by heating cold tumors with therapeutic proteins encoded by mRNA.
The potential to cure autoimmune illnesses has been opened by the confirmation that mRNA treatment can achieve tolerization in animal models of multiple sclerosis. Clinical studies involving mRNA vaccines should recruit volunteers of different ethnicities, nationalities, and ages. In addition, clinical studies should also take into account various delivery methods and schedules in order to identify the best vaccination plan, which will assist in directing the best handling, distribution, storage, and transportation practices for mRNA vaccines.
In conclusion, mRNA technology presents a significant opportunity for the development of quick, mass-produced, and environment-friendly vaccinations with improved efficacy and safety. The long-term effects of mRNA vaccines and their consequences will be revealed with the aid of data from clinical trials and future research in this area. Since low stability and limited transmission efficiency are still the key issues preventing mRNA vaccines from being clinically viable, concepts related to nanotechnology were applied, such as entrapping the vaccines within nanocarriers, primarily tissue-engineered scaffolds, liposomes, LNPs, and polymeric NPs.
In conclusion, mRNA vaccines are a groundbreaking technology with applications extending beyond infectious diseases. Their versatility and adaptability make them a promising tool in several areas of medicine and biotechnology.
References
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Authors:
Ms. Akshita Kulkarni (B. Tech. Biotechnology, Sem V student)
Dr. Ashwini Puntambekar (Assistant Professor, Protein Biochemistry Research Center)
Dr. D. Y. Patil Biotechnology and Bioinformatics Institute,
Dr. D. Y. Patil Vidyapeeth, Pune - 411033, Maharashtra, India.