Thank you qkl2 for your delivery
With the continuous variation of novel coronavirus, the infectivity has been greatly enhanced. After the outbreak of a new round of epidemics in many parts of the world, the debate about the choice of vaccination has heated up again. Among them, a highly focused topic is "whether to strengthen vaccination with vaccines of different technical routes". On May 2, 2022, Xie Xiaoliang group of Peking University uploaded an article evaluating three new Omicron subtypes BA in biorxiv 2.12.1，BA. 4 and ba 5 immune escape articles.
The data are very detailed. This study pays particular attention to the enhanced / post infection immune response based on the whole course vaccination of inactivated virus vaccine, which is the most widely used in China; In the face of rapidly evolving mutants, it is imperative to optimize the inoculation strategy.
At present, the more common vaccines include Kexing vaccine (inactivated), fubitai vaccine (mRNA), etc. Recently, the University of Hong Kong released a number of experimental data on bnt162b2 (fubitai) and coronavac (Kexing) vaccines.
In the adolescent (11 to 17 years old) population, the induction effect of two doses of mRNA vaccine is higher than that of two doses of inactivated vaccine in terms of humoral immune response. For example, the comparative data of s-specific IgG is (GM OD450 0.54 vs 1.21; GMR 0.44, 95% CI 0.40-0.49).
In terms of cellular immunogen response, the s-specific IL-2 + CD4 + T cell response in CC group (inactivated vaccine vaccinated) was lower than that in BB group (mRNA vaccinated) (0.015% vs 0.032%; GMR 0.45, 95% CI 0.28-0.72)).
In addition, based on the relationship between nab and VE in adolescents, it is inferred that the vaccine can prevent symptomatic infection of VE. The data are as follows: 2 doses of mRNA vaccine = 93%; 2 doses of inactivated vaccine = 50%; 1 dose of mRNA vaccine = 59%. It can be seen that the protective power of either one dose of mRNA vaccine or two doses of mRNA vaccine is higher than that of two doses of inactivated vaccine.
The study also drew the following conclusions: first, the S protein related antibody indexes induced by the basic immune program of mRNA vaccine were higher than those of two doses of inactivated vaccine; Second, the basic two doses of the two vaccines can induce strong T cell response, and the s-specific IL-2 + CD4 + T cell response induced by mRNA vaccine is significantly higher than that induced by inactivated vaccine.
In the study of the variation of immune response with time, there is also a large gap between mRNA vaccine and inactivated vaccine. In terms of humoral immunity, the following research data are obtained.
First, 100% of the vaccinators in the mRNA vaccine group induced anti-s protein LGG and anti RBD IgG, while only 85.7% in the inactivated vaccine group.
Second, the pseudovirus neutralizing antibody reaction found that the serum of mRNA vaccinators had 19 times higher response to wild-type nabts than that of inactivated vaccinators (Fig. 1b).
In the cellular immune dimension, the cross nab against VOCs produced by the mRNA vaccine group was significantly stronger than that of the inactivated vaccine group, and the neutralizing antibody of the former was 2.7-16 times higher than that of the latter (Fig. 2a).
Similar to the University of Hong Kong, the Chinese University of Hong Kong obtained the following experimental data after comparing the immunogenicity of the two vaccines.
First, neutralizing antibody detection - in the alternative virus neutralization test (svnt), the data of mRNA vaccine group was 93.63% ± 7.92%, which was significantly higher than that of inactivated vaccine group 52.11% ± 22.06% (P & lt; 0.0001).
Second, in the live virus neutralization test and plaque subtraction neutralization test PRNT, the neutralization titer GMT induced by mRNA vaccine was 251.60, which was 3.6 times that of PRNT50 (69.45) of inactivated vaccine (Fig. C); The neutralization titer induced by mRNA vaccine GMT: 98.91, which is 6 times that of prn90 (16.57) of inactivated vaccine (Fig. d).
In conclusion, in terms of immunogenicity, mRNA vaccine has obvious advantages over inactivated vaccine.
Different real world research conclusions
Through the research data of the University of Hong Kong and the Chinese University of Hong Kong, we can basically see the difference in the effectiveness of inactivated vaccine and mRNA vaccine. Here comes a more serious question: in the face of Omicron or other virus variants with stronger transmission in the future, what vaccine should we use for immune enhancement?
Let's first look at the research data of the epidemic situation in Hong Kong. For the protective effect of mild and moderate diseases, the data show that the third injection of mRNA vaccine and inactivated vaccine is homologous. The preventive power of the former is 71.5% and that of the latter is 42.3%, both of which have a certain protective effect, but the protective ability of mRNA vaccine is significantly stronger than that of inactivated vaccine.
Look at Brazil's research data. In terms of prevention of hospitalization or death, homologous enhancement of inactivated vaccine can improve the protection rate to a certain extent, but with the increase of time, the attenuation rate is also very fast, with rve of more than 3 months of 14.8% (95% CI 5.4 to 23.2); In terms of anti symptoms, the homologous enhancement of inactivated vaccine was almost not improved, and the rve was 4.0% (95% CI 0.2 to 7.6) 8-59 days after enhanced vaccination.
If heterologous enhancement of mRNA vaccine was used, the protection rate was significantly improved in the prevention of hospitalization or death, which was maintained for at least three months, and the rve for more than three months was 66.9% (95% CI 64.7 to 69.0).
Finally, look at the research data of Singapore. In terms of the effectiveness of preventing novel coronavirus infection, the adjusted IRR of mrna-1273 (Moderna vaccine) was 0.84 (95% CI 0.82 -0.86), coronavac (Kexing vaccine) was 2.37 (95% CI 2.29 - 2.46), and bbibp CorV (National Drug vaccine) was 1.62 (95% CI 1.43 -1.85).
In terms of prevention (95-3.95% CI, 25.0-0.3) of coronavirus, the effectiveness of coronavirus was - 59.3 (95-3.95% CI, 95-0.48). It can be seen that the inactivated vaccine is significantly weaker than the mRNA vaccine in the prevention of neocoronavirus infection and severe infection.
Heterogeneous enhancement is the best option
Through a large number of studies and real-world data, we have seen the protective power of inactivated vaccine and mRNA vaccine in different situations. In the face of more and more toxic variants, the top priority is to find the most suitable and reliable vaccination scheme. In other words, targeted adjustments should be made to the existing vaccination plan.
The comparison of the effectiveness data of mRNA vaccine and inactivated vaccine in the previous report has actually provided a scientific and feasible vaccine optimization scheme, that is, heterologous vaccine, or stronger vaccine.
There are also large-scale research data in the real world to strengthen the anti infection ability of needles after heterologous vaccination. Recently, Chile published a research report in the journal Lancet global health, which disclosed the effectiveness data of homologous booster vaccine and heterologous booster vaccine.
The study is based on about 11.17 million individuals, of which about 4.12 million have completed two doses of inactivated vaccine and one dose of booster vaccine. Among the people vaccinated with the third dose, about 1.92 million have been vaccinated with AstraZeneca, about 2.02 million have been vaccinated with mRNA, and about 190000 are still vaccinated with inactivation.
The final effectiveness data were that in the prevention of symptomatic covid-19 infection, the effectiveness of inactivation, mRNA and AstraZeneca as reinforcing needles were 78.8% (95% CI 76.8 – 80.6), 96.5% (95% CI 96.2 – 96.7) and 93.2% (95% CI 92.9 – 93.6), respectively.
Therefore, the use of more protective heterologous vaccine as booster vaccination is a more reliable vaccination scheme in the face of variant virus at present and in the future.
Not long ago, experts related to central disease control also pointed out that research data show that the increase of antibody titer of heterologous vaccination is higher than that of homologous vaccination.
What is more worth pondering is that according to the vaccine combination efficiency data released by the University of Hong Kong, according to the current domestic approximate rate of vaccination, the effective rate of two injections of Kexing and three injections of Kexing vaccine combination is only 1% for Omicron mutant strain 180 days after vaccination, while the effective rate of three injections of Kexing is only 8%.
Real world data from Brazil also showed that the effectiveness of two doses of coronavac in preventing Omicron was significantly reduced. After 180 days of inoculation with two doses of Kexing, the effectiveness of preventing symptomatic infection of Omicron was only 8.1%, and the effectiveness of preventing severe / death of Omicron was 57.0%.
According to the latest data at the end of April, the coverage rate of vaccination in China is about 53%, and there is still much room for improvement. In the face of Omicron and unknown virus variants in the future, the current relevant research progress continues. The research of Xie Xiaoliang group of Peking University mentioned at the beginning of the article found that breakthrough infection of Ba occurred after vaccination with inactivated virus vaccine 1. It is mainly induced for primitive wild type and ba 1, while the neutralizing antibodies produced were mainly aimed at the original wild-type and ba 1。 Vaccination and ba The sera of infected persons could not neutralize some strains effectively, and lacked neutralizing activity to the original wild-type and other mutant strains. Perhaps, this also proves from another dimension that the three shot inactivated vaccine is no longer the optimal solution.