A detailed explanation of ＂nucleic acid vaccine＂

This article is the original article of Kanjian Daily for the health sector. For more in-depth articles, please click: Kanjian Daily.

With the promotion of vaccination in COVID-19, many people have received vaccination notices one after another and made an appointment to vaccinate COVID-19 vaccine. But at the same time of vaccination, many people also questioned: what is the vaccine we are playing? Does it really work?In fact, there are many kinds of vaccines in Covid-19, including inactivated vaccine, adenovirus vector vaccine and mRNA vaccine, as well as COVID-19 vaccines such as recombinant subunit, synthetic peptides and DNA. Each vaccine has different ways and advantages.

Inactivated vaccine is the "base"

Inactivated vaccine is the most traditional vaccine preparation method. Inactivated vaccine can be simply understood as that by injecting artificially inactivated pathogenic microorganisms or their metabolites (antigens) into the body, the human body can recognize the antigens to produce specific antibodies. Once invaded by external specific viruses, these specific antibodies will mediate the body’s defense function and thus resist the invasion of viruses.

Inactivated vaccine is a mature technology, and its safety is good, but the production cycle is long (more than 60 days), and its immunogenicity becomes weak, so it needs multiple immunizations to strengthen the curative effect. Inactivated vaccines on the market include: Japanese encephalitis inactivated vaccine, hepatitis A inactivated vaccine, rabies vaccine, cholera vaccine, etc., which can be said to be widely used.

Figure 1: Inactivated vaccine (from IMMUNOLOGY.org)

COVID-19 inactivated vaccine, which contains inactivated virus SARS-CoV-2, still retains some antigenicity, but it will not cause the vaccinator to be infected with COVID-19; It can be recognized by the immune system and activate the immune response.After the successful establishment of immune memory, the immune system of the vaccinated person will have immune resistance to Covid-19 in the future. At present, Sinovac Kexing Bio, Sinopharm Chinese Medicine and COVID-19 Vaccine from Bharat Biotechnology are all inactivated vaccines.

However, due to the lack of activity, long production cycle and low vector conversion rate of inactivated vaccine, many countries have begun to develop the latest vaccine types …

Table 1: Some clinical trials of COVID-19 vaccine under study [1]

The development of nucleic acid vaccine is "the general trend"

As a newly emerging biological product at the gene level, nucleic acid vaccine plays a vital role in the prevention and control of many diseases such as bacteria, viruses, parasites and tumors.In recent years, with the emergence of various new diseases, the disadvantages of traditional vaccines are gradually exposed, which can no longer meet people’s needs. Traditional vaccines, such as attenuated vaccines and inactivated vaccines, are generally transformed by vectors, and their immune efficiency is low. Studies have found that attenuated vaccines may also have toxic residues, which may lead to the risk of secondary infection. As a new vaccine, nucleic acid vaccine can activate the immune mechanism of the body through specific channels, thus achieving the effect of rapid immunization, which is safer and more efficient than traditional vaccines [2].

Nucleic acid vaccines are mainly divided into DNA vaccines and RNA vaccines. DNA-based vaccines are mostly used in tumors, while the new COVID-19 vaccines currently under development are mostly mRNA-based vaccines. The inoculation method of nucleic acid vaccine and the regulation of influencing factors have great influence on inducing the expression of antigen protein in the body, especially the selection of promoter and vector. In addition, there are various inoculation methods of nucleic acid vaccine, and choosing the appropriate inoculation route of nucleic acid vaccine will help to improve the transformation rate of vaccine. In the future, nucleic acid vaccine will become an indispensable biological product in the fields of human disease prevention and treatment, and has broad application prospects.

Table 2: Some nucleic acid vaccines under research for tumors (compiled by the author)

MRNA vaccine is expected to become a "hard-core" vaccine against COVID-19 mutation quickly.

Essentially, a nucleic acid vaccine is to inject a plasmid vector with a specific pathogenic microorganism foreign antigen coding gene (mostly DNA) sequence into a specific host cell. Under the control of the vector plasmid, the foreign antigen gene is transcribed into a specific antigenic mRNA (this process usually requires the participation of a strong promoter), and a functional protein is generated through a series of signal transmission to activate the immune response.

At present, many vaccines developed by COVID-19 vaccine research and development companies are mRNA vaccines, and mRNA vaccines have obvious advantages compared with inactivated vaccines..Firstly, because mRNA vaccine does not depend on cell amplification, its detection and quality control are relatively simple. Secondly, the speed of vaccine production is also very important for the current situation because it saves the time of cell culture and expansion and greatly improves the vaccine productivity. At present, as the third generation vaccine technology, mRNA vaccine is a technical route vaccine used by many western developed countries. MRNA vaccine can accurately express antigen and activate the dual immune mechanism of "body fluid +T cells", which has strong immunogenicity and does not need adjuvant.

Figure 2: Overview of nucleic acid vaccine in COVID-19 (from IMMUNOLOGY.org)

It is worth noting that on April 6th, 2021, the top medical journal, the New England Journal of Medicine (NEJM), published a communication article from the National Institutes of Health (NIH), reporting the antibody attenuation after 6 months of inoculation with mRNA COVID-19 vaccine (mRNA-1273).

Figure 3: Anti-body persistence through 6 months after the second dose of mRNA-1273 vacuum forcovid-19

In this study, the serum of 33 patients inoculated with two doses of mRNA-1273 was analyzed. Through two neutralization test methods, pseudovirus neutralization test and live virus FRNT test, it was found that the serum neutralization activity of mRNA-1273 vaccinators of all ages continued at ID50100 and above for up to 6 months after vaccination. It can be seen from the curve in the study that the neutralization activity of mRNA-1273 reached the peak 7 days after the second inoculation.

Table 3: Time course of SARS-CoV-2 antibody binding and neutralization reaction after 3：mRNA-1273 vaccination

From the kinetic curve of antibody metabolism provided by this study, it can be seen that the serum neutralizing antibody level is very stable after inoculation with mRNA-1273, and the antibody activity in all age groups remains at a high level on the 209th day of inoculation. Moreover, this result has been verified in three different types of tests. It should be noted that the antibody level does decrease with age.

Write it at the end

Based on the advantages of mRNA vaccine, the World Health Organization (WHO) has approved the urgent use of mRNA vaccine. At present, 68 countries and regions including the United States, Britain, China and Hongkong have introduced mRNA vaccine. But even if the mRNA vaccine is so superior, there are still many disadvantages.

First of all, from the principle of action, when the mRNA vaccine is injected into the host, there is a certain chance that the foreign antigen sequence fragment will be mistakenly integrated into the genome of the organism, causing the disease of the organism [2]. Secondly, from the technical point of view, RNA itself is unstable, and mRNA is likely to be degraded when it enters the body, so it needs to be delivered by additional vectors. In addition, transportation and storage may require very strict and low temperature conditions, which will be a great challenge in research and development.

However, it is undeniable that in the clinical trial reports of various mRNA vaccines, the antibodies produced by them can be maintained in the body for at least 6 months. Some experts believe: "With the research on antibodies and other related factors of immunity after vaccination in COVID-19, it is expected that we will observe that immunity will last for a longer time [4]." It can be predicted that mRNA vaccine represents the world’s leading nucleic acid vaccine route, and together with the traditional technical route vaccine, it will form a joint phalanx of vaccine research and development, which will bring dawn to the decisive victory of global anti-epidemic.

References:

1. Xing Kai, etal., systematic evaluation of the efficacy and safety of COVID-19 vaccine. China Journal of Contemporary Pediatrics, 2021.23 (03): P.221-228.

2. Li Wei, Cao Wenjing, and Cheng Yongxiang, the latest research progress of nucleic acid vaccine. Contemporary Animal Husbandry, 2020 (09): P.16-19.

3.Doria-Rose，N.，etal.，Anti body Persistence through 6 Month safter the Second Dose of mRNA-1273 Vaccine for Covid-19.NEnglJMed，2021.

4. How long will COVID-19 vaccine "work" from a new medical perspective? NEJM publishes data on the persistence of mRNA vaccine protection. New medical perspectives, 2021.

Welcome to submit good articles on medical health. After employment, the remuneration is rich, and priority is given to the promotion of the whole platform in the health sector.

Please send the manuscript to: wangdandan@hmkx.cn