Part Five: Effectiveness, Safety and Prospects of mRNA Vaccine

 

Effectiveness

mRNA vaccines can induce adaptive immunity in the following ways:

(1) Transfection of somatic cells, such as muscle cells and epidermal cells,

(2) Transfection of immune cells in the tissues of the injection site,

(3) Transfect immune cells in secondary lymph node tissues (including lymph nodes (LN) and spleen) (Figure 1)
.

 

Figure 1 Mode of action of intramuscular injection of mRNA vaccine

 

For injected mRNA vaccines, the main considerations for effectiveness include: antigen expression level in professional antigen presenting cells (APC), its carrier efficiency, unmodified nucleoside (PAMP) form of double-stranded RNA (dsRNA) or pathogen-related molecules The optimization level of the pattern and RNA sequence (codon usage, G:C content, 5'and 3'UTR, etc.

); dendritic cells (DC) mature and migrate to secondary lymphoid tissues.

 

Figure 2 Considerations on the effectiveness of direct injection of mRNA vaccines

 

 

Safety

Compared with many current vaccination strategies (such as DNA vaccines), mRNA production is faster, more flexible, and lower in cost, and can be used for precise and individualized treatment
.

At the same time, mRNA will not be integrated into the host genome, ensuring basic safety

The safety requirements of modern preventive vaccines are very strict, because vaccines are given to healthy people
.

Since the manufacturing process of messenger RNA does not require toxic chemicals or cell cultures that may be contaminated by foreign viruses, the production of mRNA avoids the common risks of other vaccine platforms (including live viruses, viral vectors, inactivated viruses, and subunit protein vaccines).

Several different mRNA vaccines were tested in clinical studies from Phase I to Phase IIb, and the results showed that they are safe and well tolerated
.

However, recent human trials have shown that there are moderate reactions throughout the body at the injection site or different mRNA platforms, and severe reactions may occur in rare cases

Another potential safety issue may stem from the presence of extracellular RNA during the mRNA vaccination process
.

Naked extracellular RNA has been shown to increase the permeability of tightly packed endothelial cells, which may cause edema

Regulatory guidelines for evaluating the quality, safety, and effectiveness of RNA-based vaccines used to prevent infectious diseases are currently being considered
.

The focus now is to establish a manufacturing process that can provide high-quality and consistent products

 

 

prospect

The mRNA-based vaccine is a new vaccine platform with high versatility, effectiveness, simplicity, scalability, low cost and no cold chain potential
.

Importantly, mRNA-based vaccines can fill the gap between emerging pandemic infectious diseases and rapid, adequate and effective vaccine supplies

Compared with traditional vaccines, mRNA vaccine technology has great potential
.

This versatile RNA vaccine platform has advantages in the speed and cost of discovery and development, the possibility of success for many goals, and the rapid production of effective vaccines against new threats

However, it is still too early to fully understand its safety and effectiveness in the human body
.
The recently announced clinical trial results of two traditional mRNA vaccines against infectious diseases show that they are generally well tolerated and immunogenic, but according to the results of animal experiments, the response was milder than expected
.

It is necessary to further understand its mechanism of action, understand the influence of the innate immune response generated by mRNA and its delivery system, and determine how to learn from animal species to transform into humans
.

The next 5 years will be very important to the field of mRNA vaccines
.
The results of human clinical trials will enable people to have a clearer understanding of the true prospects of the technology, and in-depth understanding of the advantages and disadvantages of various mRNA technologies and delivery systems under development
.

 

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

 

 

references:

1.
Pardi N, Hogan MJ, Porter FW, Weissman D.
mRNA vaccines-a new era in vaccinology.
Nat Rev Drug Discov.
2018 Apr;17(4):261-279.
doi: 10.
1038/nrd.
2017.
243.
Epub 2018 Jan 12.
PMID: 29326426; PMCID: PMC5906799.

2.
Xu S, Yang K, Li R, Zhang L.
mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection.
Int J Mol Sci.
2020 Sep 9;21(18):6582.
doi: 10.
3390/ijms21186582.
PMID: 32916818; PMCID: PMC7554980.

3.
Banerji A, Wickner PG, Saff R, Stone CA Jr, Robinson LB, Long AA, Wolfson AR, Williams P, Khan DA, Phillips E, Blumenthal KG.
mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach.
J Allergy Clin Immunol Pract.
2021 Apr;9(4):1423-1437.
doi: 10.
1016/j.
jaip.
2020.
12.
047.
Epub 2020 Dec 31.
PMID: 33388478; PMCID: PMC7948517.

4.
Kim J, Eygeris Y, Gupta M, Sahay G.
Self-assembled mRNA vaccines.
Adv Drug Deliv Rev.
2021 Mar;170:83-112.
doi: 10.
1016/j.
addr.
2020.
12.
014.
Epub 2021 Jan 2 .
PMID: 33400957; PMCID: PMC7837307.

5.
Cagigi A, Loré K.
Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans.
Vaccines (Basel).
2021 Jan 18;9(1):61.
doi: 10.
3390/vaccines9010061.
PMID: 33477534; PMCID: PMC7831080 .

6.
Miao L, Zhang Y, Huang L.
mRNA vaccine for cancer immunotherapy.
Mol Cancer.
2021 Feb 25;20(1):41.
doi: 10.
1186/s12943-021-01335-5.
PMID: 33632261; PMCID: PMC7905014 .

7.
Wang Y, Zhang Z, Luo J, Han X, Wei Y, Wei X.
mRNA vaccine: a potential therapeutic strategy.
Mol Cancer.
2021 Feb 16;20(1):33.
doi: 10.
1186/s12943-021- 01311-z.
PMID: 33593376; PMCID: PMC7884263.

8.
Lamb YN.
BNT162b2 mRNA COVID-19 Vaccine: First Approval.
Drugs.
2021 Mar;81(4):495-501.
doi: 10.
1007/s40265-021-01480-7.
PMID: 33683637; PMCID: PMC7938284.

9.
Blakney AK, Ip S, Geall AJ.
An Update on Self-Amplifying mRNA Vaccine Development.
Vaccines (Basel).
2021 Jan 28;9(2):97.
doi: 10.
3390/vaccines9020097.
PMID: 33525396; PMCID: PMC7911542 .

10.
Huang Q, Zeng J, Yan J.
COVID-19 mRNA vaccines.
J Genet Ge

(Source: Internet, for reference only)

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