STTT Beijing University of Chemical Technology Fan Huahao and others published a long review of the research and development of new crown vaccine

iNature Vaccination is critical as SARS-CoV-2 continues to mutate and develop variants of interest (VOCs)
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Existing SARS-CoV-2 vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA and virus-like particle (VLP) vaccines
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Viral vector vaccines, protein subunit vaccines, and mRNA vaccines can induce additional cellular or humoral immune modulation, including Th cell responses and germinal center responses, and form associated memory cells, greatly enhancing their efficiency
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However, some viral vector or mRNA vaccines may be associated with complications such as thrombocytopenia and myocarditis, raising concerns about the safety of these COVID-19 vaccines
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On May 3, 2022, Huahao Fan, Yigang Tong and Lihua Song from Beijing University of Chemical Technology (Li Maochen, Wang Han, Tian Lili and Pang Zehan are the co-first authors of the article) published online on Signal Transduction and Targeted Therapy (IF=18) entitled A review article on "COVID-19 vaccine development: milestones, lessons and prospects", which systematically assesses the safety and efficacy of COVID-19 vaccines, including possible complications and risk of Differential effects in patients with AIDS, transplant recipients, and cancer patients
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Based on the current analysis, it is recommended that governments and relevant agencies continue to advance the vaccine immunization process
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At the same time, it is necessary to pay special attention to the health status of vaccines, deal with complications in a timely manner, and do a good job in vaccine development to protect the lives and health of patients
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In addition, available measures such as mix-and-match vaccination, development of new vaccines such as nanoparticle vaccines, and optimization of immune adjuvants to improve vaccine safety and efficacy could be considered
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At present, the new coronavirus is still raging around the world.
New mutant strains such as Omicron and the XE/XD mutant strain recently discovered in the UK have stronger infectivity and infection incubation period, posing a huge challenge to the efficacy of existing new crown vaccines.
Development Safe and effective vaccines and rational improvement of existing vaccination strategies are critical to further control the worldwide epidemic of SARS-CoV-2
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Figure 1.
Milestones of COVID-19 vaccine development This review provides insights into the mechanism of COVID-19 vaccine-induced immune response, existing COVID-19 vaccine platforms, COVID-19 vaccine efficacy and safety, existing vaccine optimization and improvement strategies, and clinical trials of various vaccines currently approved by the World Health Organization Trial data and real-world data, possible complications of vaccination were systematically summarized and reviewed
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In addition, the article also analyzed the pros and cons of current vaccination strategies based on the results of multiple clinical trials, and analyzed and prospected new vaccination methods (such as inhalable vaccines) and different vaccination strategies (such as heterologous booster vaccination, post-infection vaccination).
, and put forward reasonable suggestions for future new crown vaccine development and vaccination strategies
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Overall, this review has important guiding significance for the vaccination and epidemic prevention and control of the new crown
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Figure 2.
Vaccine-induced Th1 responses Numerous studies have shown that not only the production of protective antibodies can be induced after vaccination with COVID-19, but some mRNA vaccines (such as mRNA-1273, BNT162b2) and adenovirus vector vaccines (such as AZD1222) can also Trigger additional Th cell responses and germinal center responses and generate levels of memory cells that can rapidly produce antibodies or convert into effector cells upon encountering the same pathogen (eg, SARS-CoV-2)
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Figure 3.
Vaccine-induced germinal center response According to the data released by the World Health Organization, the current new crown vaccines cover the following categories: inactivated vaccines, live attenuated vaccines, vector vaccines (replicating and non-replicating), RNA vaccines, DNA vaccines Vaccines, protein subunit vaccines, and virus-like particle (VLP) vaccines
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The article systematically expounds the research and development status, advantages and disadvantages of the above-mentioned new crown vaccines, and systematically analyzes the effectiveness of the new crown vaccines approved by the World Health Organization based on animal experimental data, clinical trial data and real-world data
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In addition, the article also analyzes and introduces the existing SARS-CoV-2 VOC mutant strains Alpha, Beta, Gamma, Delta and Omicron (including the source of the mutant strain, mutation site, virus characteristics, etc.
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Figure 4.
Vaccine-induced memory cell responsesFigure 5.
Timeline of key events in COVID-19 vaccine developmentFigure 6.
Timeline of preclinical and clinical trials of approved COVID-19 vaccinesFigure 7.
System of S protein mutation in VOC In addition to the effectiveness, the safety of the new crown vaccine has also attracted much attention.
The article systematically summarizes the complications caused by various types of new crown vaccines that have been reported, and expounds and summarizes the potential pathogenesis
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By analyzing the overall effectiveness of the new crown vaccine in different populations, it provides countermeasures for the improvement of vaccination strategies
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Figure 8.
Some possible complications of COVID-19 vaccinesFigure 9.
Effects of vaccination in different populations The systematic introduction and comparison are presented, and systematic suggestions are put forward from the aspects of vaccine adjuvant improvement and new vaccine development
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In the post-epidemic era, new SARS-CoV-2 mutants represented by Omicron have higher infectivity and immune evasion capabilities.
Changing or adjusting vaccination strategies is of great significance for infection control and public health pressure relief
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In the follow-up vaccine development and epidemic prevention and control work, the following points are worth noting: (1) Although the booster dose can enhance the response of memory cells and increase the antibody titer, resulting in stronger protection, the fourth dose of inactivated vaccine Omicron mutant infection may still not be effectively prevented; (2) by optimizing the vaccine, such as changing the vaccination route (such as using inhaled vaccines to further induce mucosal immunity and protecting the upper respiratory tract), developing new vaccines (using beta and Multivalent inactivated vaccines prepared from delta mutants, mRNA vaccines prepared using the sequences of beta mutants) and sequential immunization (vaccines developed using different approaches, such as inactivated vaccines + viral vector vaccines or mRNA vaccines), will provide more Effective protection; (3) Although the use of inhalable vaccines and sequential immunization strategies can improve the efficacy of new crown vaccines, inoculation of viral vector vaccines or mRNA vaccines may lead to complications such as myocarditis and thrombosis.
effectiveness
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While newer vaccine platforms, such as mRNA vaccines, can provide more effective protection, they are less safe than inactivated vaccines
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If a multivalent inactivated vaccine is used, such as the beta + delta inactivated vaccine strategy described above, development can only be carried out after the emergence of new variants, and the development speed is lower than that of mRNA vaccines using new mutant sequences; (4) Omi The appearance of chron may indicate a change in the main site of infection of SARS-CoV-2 (other VOCs often cause lung infection), and people infected with chron of Omic tend to have milder symptoms and lower hospitalization rates than those infected with delta
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In this case, there are many asymptomatic infected people, and the use of convenient and effective antiviral drugs (especially oral drugs) will greatly alleviate the epidemic and help to end the epidemic as soon as possible
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Li Maochen from the 2018 Pharmaceutical Engineering Experiment Class of the School of Life Science and Technology, Beijing University of Chemical Technology, Dr.
Wang Han from Harbin Children's Hospital, Tian Lili and Pang Zehan from the 2018 Bioengineering Experiment Class are the co-first authors of this paper
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Associate Professor Fan Huahao from the School of Life Science and Technology, Beijing University of Chemical Technology is the main corresponding author of this article
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Article link: https://