The Lancet: Protein subunit vaccine booster after two doses of inactivated vaccine can produce high neutralization protection against new coronavirus and its variants

Title: A protein subunit vaccine booster following two doses of inactivated SARS-CoV-2 vaccine provides high neutralisation of SARS-CoV-2 and its variants in mice
Journal: The Lancet Microbe (impact factor 86.
2)
Author and unit: Institute of Microbiology, Chinese Academy of Sciences Zhao Xin from the Gao Fu team of the Key Laboratory of Pathogenic Microbiology and Immunology is the corresponding author of the paper
.

Zhang Rong, the first author of the Laboratory of Animal Science and Veterinary Animal Infectious Diseases in Nanning, China
.

Vazyme Collaborative Product: 2019-nCoV (SARS-CoV-2) Spike (S) Protein (His-Avi)
Background
of the research CoV-2 vaccination provides good protection against severe illness and death from COVID-19; however, decreased immunity to SARS-CoV-2 in vaccinated individuals occurred 6 months after the last dose of the vaccine
.

Booster vaccinations (third doses) have been proposed and started in many countries
.
Research ideas and results show
that this study selected the inactivated vaccine BBIBP-CorV (Sinopharm) and the receptor binding domain (RBD)-based tandem repeat dimer protein subunit vaccine ZF2001
.

The effects of different combinations of the two vaccines in the two-dose vaccination scheme and the three-dose vaccination scheme on the content of RBD antibodies, S protein antibodies and the activity of neutralizing antibodies in vivo were explored, and the effects of different combined vaccines on mutant viruses were also explored.
effect
.
It provides strong support for the effect of ZF2001 as a booster
.
1.
Two-dose vaccination, primary immunization-second immunization scheme
Figure 1: Time course of vaccine immunization and sampling in two-dose experimental group and control group Figure 2: Changes in indicators of each experimental group in the two-dose scheme group Five groups were evaluated in the experiment : BBIBP-CorV-ZF2001 (one dose of BBIBP-CorV followed by the second dose of ZF2001), ZF2001-BBBP-CorV group (one dose of ZF20011 followed by the second dose of BBIBP-CorV), ZF2001-ZF2001 (one dose of ZF2001 followed by the second dose) ZF2001), BBIBB-CorV-BBIBP-CorV (a second dose of BBIBP-CorV after one dose of BBIBP-CorV), and placebo
.
Figure 1 shows the time course of vaccine immunization and sampling for the two-dose regimen, a and b represent the time course and vaccination for the two-dose regimen (n=10 per group)
.

In this experiment, all groups were pressed b, with an interval of 21 days
.

Blood was collected on day 19 and day 35, respectively
.
Figure 2a and b show serum IgG titers against SARS-CoV-2 RBD (a) and spike (S) protein (b) detected by ELISA in the two-dose regimen group
.

c and d show 50% pseudovirus neutralization (pVNT50) of SARS-CoV-2 virus wild-type (c) and variant (d) spike pseudoviruses in serum collected from the two-dose regimen group
.
2.
Three-dose vaccination, primary immunization-second immunization-boost regimen
Figure 3: Time course of vaccine immunization and sampling in the three-dose experimental and control groupsFigure 4: Changes in indicators in each experimental group in the two-dose regimen Four groups were evaluated: BBIBP-BBIBP-ZF2001 (two doses of BBIBP-CorV , followed by a booster shot of ZF2001), BBIBP-BBIBP-BBIBP (two doses of BBIBP-CorV, followed by a third booster shot of BBIBP-CorV), BBIBP-BBIBP group (two doses of BBIP-CorV, no booster shot) and placebo group
.
Figure 3 is a schematic diagram of the three-dose regimen (placebo group and BBIBP>BBIBP>ZF2001 group; n=8)
.

In this experiment, mice received either 2 doses (BBIBP>BBIBP group) or 3 doses of vaccine or placebo as described in D, separated by 21 days
.

Blood samples were collected on day 19, day 35 or day 40 (day 35 in BBIBP>BBIBP group, day 40 in other groups) and day 49, respectively
.
Figure 4e and f show the IgG titers of serum anti-SARS-CoV-2 RBD (e) and spike (S) protein (f) in the three-dose regimen group detected by ELISA
.

g and h show 50% pseudovirus neutralization (pVNT50) of sera collected from the three-dose regimen group against SARS-CoV-2 wild-type virus wild-type (g) and variant echinoviruses
.
In summary, the research team designed and analyzed the effect of different combinations of vaccines: In the study of different combinations of two doses of vaccines, it was found that BBIBP (first dose)-ZF2001 (second dose) had the best effect, which was better than other two-dose vaccine combinations.
Neutralizing antibody activity is 4-14.
5 times higher
.

The three-dose vaccine was more effective than the two-dose vaccine
.

The BBIBP (first dose)-BBIBP (second dose)-ZF2001 (third dose) method with recombinant protein as a booster can produce stronger levels of RBD protein-binding antibodies, S protein-binding antibodies and neutralizing antibodies than The effect of the BBIBP-BBIBP-BBIBP method with inactivated virus as a booster was 3.
4 times higher; at the same time, the BBIBP-BBIBP-ZF2001 method with recombinant protein as a booster also had a better effect on mutant viruses that are more prone to immune escape.
Strong antibody immune effect
.

These studies provide strong support for the efficacy of ZF2001 as a booster
.
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