Part III: mRNA vaccination and its mechanism of triggering the immune response

The location of the vaccination affects the induced immune response

In addition to the vaccine component itself, the delivery method and location of the vaccine also affect its effectiveness (Figure 1)
.

Figure 1 Immune response induced by mRNA injection in different parts

The figure lists the advantages and disadvantages of the different methods
.

Once the mRNA molecule is released from LNP into the cytoplasm, it is sensed by toll-like receptors (TLR) such as TLR3 or 7/8.
Retinoic acid-inducing gene (RIG)-I is promoted by retinoic acid-inducing gene (RIG)-I, type I Interferon (IFN) is secreted into the extracellular matrix
.

Figure 2 The reaction of cells ingesting LNP-coated mRNA vaccine

Figure 3 The effect of mRNA vaccine on immune function

a) The influence of exogenous mRNA on innate immunity
.

Figure 4, Figure 5 and Figure 6 show how mRNA vaccines trigger natural immune responses
.

Figure 4 Exogenous mRNA triggers the innate immune response mechanism

The mRNA vaccine synthesized by IVT can be recognized by PRR (including endosomal TLR3, -7, -8 and cytoplasmic innate immune receptors RIG-I and MDA5)
.

Figure 5 mRNA in vitro transcription and innate immune activation

(A) In vitro transcription of mRNA
.

(B) RNA translation and antigen presentation
.

(C) Self-assisting effect
.

Figure 6 Innate immune induction of mRNA vaccine

Dendritic cells (DC) have innate immunity to two mRNA vaccines
.
The RNA sensor is yellow, the antigen is red, the DC maturation factor is green, and the peptide-major histocompatibility complex (MHC) complex is light blue and red; an example of a lipid nanoparticle carrier is shown in the upper right corner
.
This figure shows a non-exhaustive list of the main known RNA receptors, which help to identify double-stranded and unmodified single-stranded RNA, select unmodified, unpurified (part a) and nucleoside modifications, and quickly Protein liquid chromatography (FPLC) purification (Part b) mRNA is used to illustrate two forms of mRNA vaccines, with and without known forms of mRNA sensing
.
The dashed arrow indicates a decrease in antigen expression
.
Term explanation: Ag, antigen; PKR, interferon-induced double-stranded RNA activated protein kinase; MDA5, interferon-induced helicase C domain protein 1 (also known as IFIH1); IFN, interferon; m1ψ, 1- Methyl pseudouridine; OAS, 2'-5'-oligoadenylate synthase; TLR, Toll-like receptor
.

Figure 7 shows the mechanism by which mRNA vaccine triggers the body's adaptive immune response
.

Figure 7 Adaptive immune response triggered by mRNA vaccination

Local inflammation at the injection site promotes the infiltration of immune cells, including neutrophils, monocytes, myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC)
.
Neutrophils can absorb LNP efficiently, and monocytes and mdc can translate mRNA more efficiently
.
Type I interferon (IFN) is stimulated to secrete
.
The mRNA/LNP and protein antigens will diffuse, and the cells will migrate to the vaccine-draining lymph nodes
.
The presentation of antigens to T cells and the interaction of antigens with B cells all occur at these sites
.
This leads to the formation of a germinal center, which produces memory B cells that reside in the bone marrow and plasma cells that produce antibodies
.

Overview of the development of mRNA vaccines: part one

Overview of the development of mRNA vaccines: part two

Overview of the development of mRNA vaccines: part three

Overview of the development of mRNA vaccines: part four

Overview of the development of mRNA vaccines: Part 5

(Source: Internet, for reference only)