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RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

ABSTRACT: mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled efficiency and success. The strategy relies on the delivery of an RNA transcript that carries the sequence of an antigenic molecule into the body's cells where the antigen is manufactured. The lack of use of infectious pathogens and the fact that they are made of nucleic acids render these vaccines a favorable alternative to other vaccination modalities. However, mRNA vaccination still suffers from a great deal of hurdles starting from their safety, cellular delivery, uptake and response to their manufacturing, logistics and storage. In this review, we examine the premise of RNA vaccination starting from their conceptualization to their clinical applications. We also thoroughly discuss the advances in the field of RNA vaccination for infectious diseases. Finally, we discuss the challenges impeding their progress and shed light on potential areas of research in the field.

SUBMITTER: Abdelzaher HM

PROVIDER: S-EPMC8622374 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

Abdelzaher Hana M HM Gabr Asmaa S AS Gabr Asmaa S AS Saleh Basma M BM Abdel Gawad Rana M RM Nour Ahmed A AA Abdelanser Anwar A

Vaccines 20211020 11

mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled efficiency and success. The strategy relies on the delivery of an RNA transcript that carries the sequence of an antigenic molecule into the body's cells where the antigen is manufactured. The lack of use of infe ...[more]

PMID: 34835142

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Project description:Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. STATEMENT OF SIGNIFICANCE: This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development.

Project description:Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette-Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.

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RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

Publications

RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

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