Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic

Jain, Samagra; Venkataraman, Abhijeet; Wechsler, Marissa E.; Peppas, Nicholas A.

doi:10.1016/j.addr.2021.114000

Cited by 96 publications

(59 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The immune stimulatory activity of mRNA is generated by activation of RNA sensors such as the TLR3, TLR7, TLR8, RIG-I, and MDA5 in cells. This activity can be optimized by adjusting the structural features of mRNA in the vaccine, which include the 5 cap, structurally modified nucleotides, 5 and 3 untranslated regions, and the poly(A) region [243][244][245]. Another strategy to tailor the immunogenicity of mRNA vaccine is co-formulating it with additional adjuvant.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Yang

Tseng

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade there has been increased developments on adjuvants for human vaccines. The development of adjuvants has paralleled our increased understanding of the molecular mechanisms for the pattern recognition receptor (PRR)-mediated activation of immune responses. Toll-like receptors (TLRs) are a group of PRRs that recognize microbial pathogens to initiate a host’s response to infection. Activation of TLRs triggers potent and immediate innate immune responses, which leads to subsequent adaptive immune responses. Therefore, these TLRs are ideal targets for the development of effective adjuvants. To date, TLR agonists such as monophosphoryl lipid A (MPL) and CpG-1018 have been formulated in licensed vaccines for their adjuvant activity, and other TLR agonists are being developed for this purpose. The COVID-19 pandemic has also accelerated clinical research of vaccines containing TLR agonist-based adjuvants. In this paper, we reviewed the agonists for TLR activation and the molecular mechanisms associated with the adjuvants’ effects on TLR activation, emphasizing recent advances in the development of TLR agonist-based vaccine adjuvants for infectious diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Yang

Tseng

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…These bacteria are known to infect the host by crossing the mucosal barriers of the GIT. Currently available vaccines are delivered intravenously or through intramuscular route and can provide cellular immunity, but not directly at the mucosal interface [ 37 ]. The risk of infection can be significantly reduced by decreasing bacterial load in the GIT before entering systemic circulation.…”

Section: Prospects Of the Oral Delivery Of Nucleic Acidsmentioning

confidence: 99%

Oral Delivery of Nucleic Acid Therapies for Local and Systemic Action

et al. 2022

View full text Add to dashboard Cite

Nucleic acid (NA) therapy has gained importance over the past decade due to its high degree of selectivity and minimal toxic effects over conventional drugs. Currently, intravenous (IV) or intramuscular (IM) formulations constitute majority of the marketed formulations containing nucleic acids. However, oral administration is traditionally preferred due to ease of administration as well as higher patient compliance. To leverage the benefits of oral delivery for NA therapy, the NA of interest must be delivered to the target site avoiding all degrading and inhibiting factors during its transition through the gastrointestinal tract. The oral route presents myriad of challenges to NA delivery, making formulation development challenging. Researchers in the last few decades have formulated various delivery systems to overcome such challenges and several reviews summarize and discuss these strategies in detail. However, there is a need to differentiate between the approaches based on target so that in future, delivery strategies can be developed according to the goal of the study and for efficient delivery to the desired site. The goal of this review is to summarize the mechanisms for target specific delivery, list and discuss the formulation strategies used for oral delivery of NA therapies and delineate the similarities and differences between local and systemic targeting oral delivery systems and current challenges.

show abstract

“…Long-term investment in biomedical research resulted in the rise of US research to a preeminent position in the world and the development of the knowledge base to combat disease and save lives. One recent illustration is the investment in basic research into mRNA vaccines, which led to the remarkably rapid development of highly effective vaccines against SARS-CoV2 during the pandemic (1, 2). During the years of a flat NIH budget, concerns about sustaining the biomedical research enterprise re-emerged amid concerns that the standing of US biomedical research in the world would erode and the development of medicines to manage disease would be impaired.…”

Section: Introductionmentioning

confidence: 99%

Research Productivity and Training Support for Doctoral Students in the Biological and Biomedical Sciences

Schaller

2022

Preprint

View full text Add to dashboard Cite

Training of doctoral students as part of the next generation of the biomedical workforce is essential for sustaining the scientific enterprise in the US. Training of doctoral students primarily occurs at institutions of higher education and these trainees comprise an important part of the workforce at these institutions. Federal investment in the support of doctoral students in the biological and biomedical sciences is distributed differently than the distribution of students across different types of institutions, e.g. Public vs Private. Institutions in states that historically receive less federal support for research also receive less support for doctoral student training. Analysis of F31 awardees at different types of institution reveal little difference in research productivity and subsequent receipt of additional NIH awards. Analysis of a large cohort of doctoral students at different types of institutions also reveal little difference in research productivity, with the exception of citations. Thus, training outcomes, which are related to the quality of the student and training environment, are similar across different institutions. Factors that correlate with F31 funding include R01 funding levels and program size. The findings suggest strategies for institutions to increase success at securing F31s and modification of policy to promote more equitable distribution of F31s across institutions.

show abstract

Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic

Abstract: Graphical abstract

Cited by 96 publications

References 87 publications

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

Oral Delivery of Nucleic Acid Therapies for Local and Systemic Action

Research Productivity and Training Support for Doctoral Students in the Biological and Biomedical Sciences

Contact Info

Product

Resources

About