The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted constant attention while the toll of deaths and infections keeps growing around the world. In order to meet the urgent demand of a SARS-CoV-2 vaccine, different kinds of immunization approaches have been employed. Among them, mRNA vaccines stand out as they can be easily and rapidly developed with no potential risk of infection.
However, there are also some bottlenecks with mRNA therapy, and the delivery efficiency of mRNA to target cells and tissues is among the most challenging. High susceptibility to degradation by omnipresent ribonucleases (RNases), together with inherent negative charge, hinder the successful delivery of mRNA to cells and subsequent translocation across the negatively charged cell membrane. Therefore, a carrier is needed to protect mRNA from degradation and facilitate cellular uptake during the delivery.
Recently, Dr. Dan Peer’s team designed a lipid nanoparticle-based RBD-hFc (human Fc-conjugated receptor-binding domain) mRNA vaccine using a preliminary in vivo screen of structurally different ionizable lipid-based nanoparticles to achieve high delivery efficiency of mRNA (ACS nano, 2021).
In this study, the researchers first synthesized and selected 5 amino lipids (lipid 2, 5,10,14 and 15, Fig.1A) and then mix them with mRNA through a microfluidic mixture device to create lipid nanoparticles (LNPs #2, 5,10,14 and 15, Fig.1B).
Figure 1. Schematic illustrations of the structures of the lipids (A) and LNP synthesis (B)
To move forward, they conducted a luciferase mRNA-based in vivo screen to evaluate the in vivo efficiency of the LNPs in terms of distribution, protein expression efficiency, and kinetics. The results showed that LNP #14 and #15 were superior to other formulations in terms of protein expression level and its duration in all three routes of administration (intradermal, intramuscular or subcutaneous injection). Hence, the immune response that developed toward the luciferase protein related to those two LNPs were further examined.
Given the fact that RBD-hFc-fusion protein can be used as an improved antigen for vaccination in regard to enhancing the immunologic response to the RBD protein, they chose LNP#14 to encapsulate RBD-hFc mRNA as it led to a strong cellular response and a significant neutralizing response was observed in LNP #14-encapsulated RBD-hFc mRNA vaccinated mice while naked RBD-hFc mRNA immunization was unable to elicit detectable humoral or cellular responses before or after the boost. The data demonstrated the potential of LNP#14-based mRNA as a promising candidate for a COVID-19 vaccine.
Their remarkable work, as concluded by themselves, substantiates the concept that the development of an efficacious LNP-based mRNA vaccine in general and LNP-based RBD-hFc mRNA vaccine in particular may benefit from a judicious inspection of the lipid component of the formulation.
With the help of Dr. Dan Peer's team, MolecularCloud has initiated a reward-winning campaign for this specific topic "nano-based mRNA vaccines". As long as you leave a good comment on the topic or get the first perfect score from the related quiz below, you'll have a chance to win yourself a $20 gift card.
*MolecularCloud reserves the right of final explanation for details of this campaign. If there's any further question, please feel free to contact us at firstname.lastname@example.org.
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Q1: Can lipid nanoparticles help enhancing mRNA vaccine delivery? (1 mark)
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Q2: Which of the following is the best carrier for mRNA vaccine delivery? (2 marks)
Q3: When was the 1st RNA vaccine approved for human use? (3 marks)
Q4: Which of the following is NOT an advantage of mRNA vaccines over traditional ones? (4 marks)
Q5: Have previous reported LNP-based RBD mRNA vaccines pursued the effect of LNP lipid composition on immunogenicity? (5 marks)