On April 10, the Joint Prevention and Control Mechanism of the State Council issued the "Vaccination Work Plan for Responding to the Recent Outbreak of New Coronavirus Infection" (hereinafter referred to as the "Plan"), which refers to the focus of emerging stage vaccination for different target groups and filling the gap in immunization levels, involving people who have not completed basic immunization, and people who are not infected and have not completed the established immunization schedule (including booster shots, etc.).
Specifically, people aged 3-17 need to complete 2 doses of inactivated vaccine or 3 doses of Zhifei recombinant protein vaccine for basic immunization; People over 18 years old should complete the first dose of booster immunization on the basis of basic immunization, among which people with high-risk infection, elderly people over 60 years old, people with more serious underlying diseases and immunocompromised people need to complete the second booster dose.
Who needs to be vaccinated?
"At present, the overall epidemic situation in the country is in a state of local sporadic distribution, but the new crown virus has not disappeared, and the spread of the virus in the population still persists. At this stage, some groups still need to be vaccinated to further strengthen their autoimmune ability and fill the gap in immunity level. The interpretation of the "Plan" released on the official website of the National Health Commission pointed out.
In fact, after the outbreak of the epidemic at the beginning of the year, relevant health and disease control departments and many experts have publicly emphasized many times that there is still strong immune protection within 3-6 months after infection. But now that more than half of the time has passed, with the lifting of various prevention and control policies and the decline in antibody levels in infected people, the issue of secondary infection has once again attracted attention.
On April 8, the Chinese Center for Disease Control and Prevention released the latest issue of the "National Novel Coronavirus Infection Epidemic Situation", on April 6, although the number of positive new coronavirus nucleic acid tests reported by various provinces decreased, the test positive rate reached 1.4%, which was a full double compared with the previous data released on March 25 and April 1.
Jin Dongyan, a professor at the School of Biomedical Sciences at the University of Hong Kong, told the "medical community" that in terms of the positive ratio, it may slowly rise in the next few months, sporadically distributed in a local, "point-like" form, only a fraction of the first round of the epidemic, in which people suffering from underlying diseases and elderly people who are not positive may be the first to face the risk of primary infection, while those who are already positive have the risk of secondary infection.
"Therefore, the biggest highlight of this plan is that it shows that the new crown vaccination can be initiated after 3 months of infection." Jin Dongyan said. According to the interpretation of the Plan, the protective antibodies acquired by vaccination and infection will decay over time. From a global perspective, it is a consensus that people at high risk of severe disease and death should be vaccinated against the new coronavirus 3 months after infection, which is conducive to providing them with better protection in subsequent outbreaks.
"For high-risk groups such as the elderly, even if they have been infected, the level of immune protection in the body will begin to decline rapidly after 3 months, and it is now necessary to increase mixed immunity through vaccination." "At the same time, if you want to reduce reinfection more effectively, you will need to receive booster shots against epidemic strains every six months or more in the future," Jin said. ”
Virology expert Chang Rongshan also said that revaccination is the most direct and effective way to protect the elderly and avoid secondary infection, but he believes that the most suitable vaccination time is the end of this year, before autumn and winter.
"Even if secondary infection occurs in the next few months, it will only spread in a small area, and the real peak of infection on a certain scale is predicted to be in the autumn and winter of this year." Chang Rongshan said, "The protective effect of the vaccine will weaken over time, and unless another dose is given at that time, the protective effect produced now may not be enough to cope with the epidemic at the end of the year." ”
For non-high-risk groups, both experts told the "medical community" that future vaccinations will rely more on individual choices because there is less risk of serious clinical consequences after infection.
"Repeated publicity about new crown vaccination, the public will gradually fatigue, coupled with the gradual 'habituation' of the new crown virus, the willingness to vaccinate will become lower and lower, this has already happened overseas." Jin Dongyan said, "Therefore, in the case of limited resources, more energy should be focused on promoting the vaccination of high-risk groups." ”
15 vaccines, which one to administer?
According to the Plan and its corresponding interpretations, sequential booster immunization is recommended in the selection of vaccines, and it is emphasized that sequential immunization can provide more comprehensive protection for individuals.
The so-called "sequential booster" refers to a vaccine that takes a different technical route than the previous shot. At present, there are 15 approved new crown vaccines in mainland China, including 5 inactivated vaccines, 6 recombinant protein vaccines, 3 vector vaccines (adenovirus vector, influenza virus vector) and 1 mRNA vaccine.
In terms of vaccine selection, the "Plan" specifically proposes that among adults, the booster immunization of people who have not been infected with the new crown and the basic immunity of those who have been infected with the new crown are preferentially recommended to use the recombinant new crown virus 4-valent S trimer protein vaccine of Shenzhou cell and the new crown virus mRNA vaccination of CSPC Group.
At present, Shenzhou 4-valent recombinant protein vaccine and stone medicine mRNA vaccine are the only two new crown vaccines approved in mainland China, covering the Omicron variant, and have been approved for emergency use at the end of March this year. According to the recommendations of the vaccine research and development special class of the scientific research group of the joint prevention and control mechanism of the State Council, the Shenzhou cell recombinant new coronavirus 4valent S trimeric protein vaccine contains the antigen components of the four variants of the new coronavirus Alpha, Beta, Delta and Omicron (BA.1), and the new coronavirus mRNA vaccine of CSPC covers the core mutation site of Omicron, which has a good cross-protection effect against the Omicron strain.
On November 15, 2022, the preliminary phase III. data of its 4-valent recombinant protein vaccine released on the official website of "Shenzhou Cell" showed that the heterologous booster vaccination for the neutralizing antibody titer of BA.5 live virus was 8.1 times higher than that of homologous inactivated vaccine.
As the first approved mRNA vaccine in mainland China, the stone medicine mRNA vaccine has attracted widespread attention. According to the protective data disclosed by the company, after 1 dose of booster vaccination, the titer of neutralizing antibody against OmicronBA.5 within 14 days was 83 times that before booster vaccination, and sequential booster immunization had a good cross-neutralizing effect on OmicronBA.5, BQ.1.1, XBB.1.5 and other strains.
The Zhuhai Lizhu new crown recombinant protein vaccine included in the "Program" also has excellent phase III. data. The results showed that heterologous vaccination in the early stages of the Omicron outbreak was 47.8% more effective in preventing new crown infection than with two doses of inactivated vaccine. Zhifei Biotech's new crown recombinant protein vaccine also appeared in the top issue of the New England Journal of Medicine this year because of its excellent phase III data.
In addition, CanSino inhaled adenovirus vaccine has also been given high hopes. Data show that in addition to humoral immunity and cellular immunity, it can also trigger mucosal immunity, activate immune cells in the mucosal tissues of the nose and respiratory tract, and act as sentinels at the site of infection.
On September 6 last year, the front-page headline of Nature reported that in principle, this type of new crown vaccine is expected to make up for the lack of "infection prevention". However, because the specific research data of "mucosal immunity" has not yet been disclosed, Jin Dongyan told the "medical community" that in the current epidemic of the Omicron variant, its comprehensive protective effect still needs to refer to real-world data.
In fact, it is not only inhaled adenovirus vaccines that need to wait for more complete data, Jin Dongyan told the "medical community" that among the existing approved vaccines in the mainland, the 4-valent recombinant protein and mRNA vaccines covering the Omicron variant are theoretically recommended, but in addition to the real-world effect remains to be seen, "The complete research data of these two vaccines have not yet been published, and it is difficult to determine the effectiveness of the actual post-vaccination protection effect." ”
Virology expert Chang Rongshan also believes that according to the disclosed data, the new crown recombinant protein multivalent vaccine or mRNA vaccine is heterologous vaccination, and the efficacy is comparable to that of overseas monovalent mRNA vaccine. "However, since the complete data for Phase III has not been published, the partially disclosed information cannot fully explain the problem."
Why infected people don't need an "inactivated vaccine"
At present, most of the basic immunization of the new crown vaccine in the mainland uses inactivated vaccines.
However, among the vaccine options given in the Plan, in addition to being excluded from the program due to "sequential booster" reasons, inactivated vaccines are also not included for people who have been infected but have not completed primary immunization.
Virology expert Chang Rongshan analyzed that the impact of "antigenic original sin", that is, "immune imprinting", may be part of the reason.
On January 25 this year, the journal Cell Research published a new study from a number of institutions in China, proposing that inactivated vaccines prepared from the original strain may cause "antigenic original sin". According to this theory, if you have previously been exposed to the original strain of the new crown or the corresponding vaccine, and then are infected by other variants, the immune system will preferentially activate the immune response against the original strain, and the proportion of specific antibodies against the new strain will decrease.
This study investigated serum samples from 135 people with BA.2 breakthrough infection and found that infected people who received Omicron BA.2 breakthrough infection had lower levels of neutralizing antibodies to Omicron BA.2, BA.4 and BA.5 compared with two doses of inactivated vaccine.
"After receiving the 'inactivated vaccine of the original strain' and facing the new coronavirus infection again, the immune system first recognizes and produces antibodies that may be against the S protein of the inactivated vaccine, and does not recognize the Omicron variant antigen, which has a large difference in immunogenicity." Chang Rongshan analyzes the "medical community".
"On the other hand, even if it is still the original strain of the vaccine, through heterologous reinforcement, the use of subunit vaccines dominated by 'antigen fragments', or targeted antigens produced by gene expression, etc., can offset the negative effects of some 'immune imprinting'." Chang Rongshan said. According to the Plan, including "primary" adenovirus vaccines and recombinant protein vaccines, they are still on the recommended vaccination list.
It is worth noting that for people who have not completed basic immunization and have not been infected with the new crown, the "Plan" still recommends the use of inactivated vaccines to complete basic vaccination, Chang Rongshan believes that this is mainly because the current round of people infected with the new crown, the body already has antibodies against the Omicron variant, at this time if the "original inactivated vaccine" is vaccinated, it will offset part of the immunity generated after infection.
However, Chang Rongshan reminded that the actual negative impact of "original sin" new crown infection cannot be quantified at present, and cannot be simply summarized as "it is better not to vaccinate", but only to suggest that in the case of conditions, a more appropriate vaccination strategy is preferred. The aforementioned study also found that despite the possible "antigenic original sin", the infected people in the "inactivated vaccine group" were milder, and 1/3 of the unvaccinated group had severe clinical symptoms.
At present, for people aged 3 to 17, there are only 3 inactivated vaccines and one recombinant protein vaccine approved for vaccination in the mainland, and according to the Plan, this population should still choose these four vaccines to complete primary immunization according to relevant indications.
Mentor experts
Chang Rongshan virologist
Jin Dongyan is a professor at the School of Biomedical Sciences, The University of Hong Kong
Source: Medical community
Responsible editor: Tian Dongliang
Editor: Zhao Jing
Written by Ling Jun
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