Omikeron is the most serious mutation that has emerged to date, with more than 30 mutations in spike proteins, 15 of which occur in the receptor binding domain (RBD). This COVID-19 strain poses new challenges to both scientific research and epidemic prevention decisions. A recent study published in the top academic journal Nature points out that for the country, a key question is whether the inactivated vaccine that has been mass-administered also has a critical protection effect on the Omikejung variant.
On January 28, Nature published a study jointly completed online by researchers from research institutions and units such as the Institute of Biophysics of the Chinese Academy of Sciences, the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences, the Institute of Microbiology and Epidemiology of the Academy of Military Medicine of the Academy of Military Sciences, the China Institute of Food and Drug Control (NIFDC), and Beijing Kexing Biological Products Co., Ltd. The research team conducted a systematic analysis of stock-neutralizing antibody titers and memory B lymphocyte antibody lineages in the serum of CoronaVac-vaccinated volunteers.
The study was led by Researcher Wang Xiangxi, head of the Research Group of the Institute of Biophysics of the Chinese Academy of Sciences and the Key Laboratory of Infection and Immunology of the Chinese Academy of Sciences, and other corresponding authors included Qin Chengfeng, researcher of the Institute of Microbiology and Epidemiology of the Academy of Military Medicine of the Academy of Military Sciences, Wang Youchun, chief expert of vaccine testing of the China Institute of Food and Drug Testing, and Qin Chuan, director of the Institute of Medical Laboratory Animals of the Chinese Academy of Medical Sciences.
The paper mentions that while the currently approved COVID-19 vaccine continues to be effective against serious illness and death caused by the Delta strain, including delta variants, a third dose of vaccine and even the development of a new vaccine is needed due to the decline in immunity caused by viral mutations and large-scale breakthrough infections.
Previously, on December 8, 2021, Pfizer announced that a preliminary laboratory study showed that three doses of the Pfizer/Biontech mRNA covid-19 vaccine BNT162b2 can neutralize the new coronavirus Omiljung variant strain. Administering three doses of the vaccine increased the neutralizing antibody titer by a factor of 25 compared to the two-dose vaccine.
The research team believes that these preliminary data on the neutralization sensitivity of Omiqueron need further independent verification, and the clinical impact of natural immunity and vaccine-induced immunity in preventing infections and serious diseases also needs to be urgently investigated. For the country, large-scale inactivated vaccines have been vaccinated so far, does this also have a critical protective effect on the Omiljung variant? How necessary is the need for three doses?
In this study, Wang Xiangxi et al. collected the serums of 60 volunteers who had received two doses (0 and 1 month procedures) and 60 volunteers who had received three doses (0, 1 and 7 months) of inactivated vaccines, and assessed their neutralizing titer on the original and Omikejong variants through live COVID-19 neutralization experiments. None of the volunteers had contracted THE virus prior to the study, which used blood samples collected 4 weeks after the last vaccination.
Evolution and neutralization characteristics of the Omikejong mutant strain.
The data showed that the geometric mean semi-maximum neutral titers (GMT NT50) of the wild-type (WT) virus, Delta and Omiljunn variants of volunteers receiving three doses of COVID-19 inactivated vaccine were 253.9, 77.8 and 15.4, respectively. Semi-maximum neutralizing titers for Delta and Omikeron were reduced by an average of 3.3-fold and 16.5-fold, respectively, compared to wild-type viruses. Three of the 60 volunteers had less than 8 titers of NT50 on Aomi Kerong. That is, the sero-positive rate of neutralizing antibodies to Omikeron by volunteers receiving three doses of COVID-19 inactivated vaccine was 95%.
However, they mentioned in the study that what is more noteworthy at the moment is the effectiveness of the two-dose vaccination regimen for Omilon infection. In the two-dose inoculation group, the NT50 titer for Delta was 6.6 compared to wild-type (WT) virus, a 5.1-fold reduction. Notably, none of the 60 volunteers had serum samples of NT50 titers greater than 8 for Aumechjong.
These results indicate that 2 doses of inactivated vaccine have a poor ability to neutralize the mutant strain of COVID-19, and that 3rd dose of inactivated vaccine can improve the titer of neutralizing antibodies in the body. However, neutralizing antibody titers against the Omikejung mutant strain remain low. The team believes their data is consistent with previous observations that three doses of inactivated vaccination enhance the neutralization breadth of the SARS-CoV-2 variant.
Strengthens broad-spectrum neutralizing antibody signatures in needle volunteers.
It is worth noting that after existing vaccinations, the level of neutralizing antibodies in the serum stock is not enough to adequately contain breakthrough infections, so why is it effective to provide critical illness protection?
The research team isolated immunoglobulin (IgG+) memory B cells from the peripheral blood mononuclear cells (PBMCs) of 4 3-dose vaccinators, obtained the sequence of the heavy and light chain variable regions of the antibody and recombined to express 323 antibodies in vitro. They found that 163 antibodies recognized the virus RBD, 100 antibodies recognized NTD, and 51 antibodies recognized S2. The test results also showed that almost all RBD-binding antibodies could bind to wild-type strains, of which 127 antibodies were neutralizing activity against both wild-type strains of real and pseudoviruses, and they selected these antibodies for further study.
Of these 127 antibodies, more than 93% exhibited extensive binding activity against most of the variants of interest and interest. Notably, 85% of these antibodies cross-react with Omikejong RBD.
In contrast, about 80 percent of the NTD-binding antibodies lost their cross-reactivity with Omikeron. In addition, due to the large diversity of NTDs, the cross-reactivity of NTD antibodies to the other four strains of concern is also relatively poor.
Their study also found that 31 strains of antibodies binding to the RBD region were able to potently neutralize wild-type and all strains of concerned variants of pseudoviruses and true viruses, with semi-inhibitory concentrations of IC50 between 0.002 and 0.800 μg/ml. Of these, 30 antibodies are able to directly block the binding of RBD to ACE2.
Of the 31 broad-spectrum potent antibodies isolated in the study, 13 antibodies were less than 0.02 ug/ml against the IC50 of Omikron, which was 10-40 times the neutralization activity of Vir-7831 of GlaxoSmithKline and Vir Biotechnology (GSK/Vir) and DXP-604, which was still in clinical trials in China.
Representative antibodies are broad and effective in the structural basis of neutralizing action.
The research team also selected four antibodies for further structural biology analysis, of which XGv347 (class II antibody) and XGv289 (class IV antibody) were extremely neutralizing to all the strains of concern, including Omilon.
They also identified the interaction of these antibodies with the Omiljung spike protein and identified a mutation in the spike protein, G446S, which is more resistant to a class of antibodies that bind to the receptor-binding domain and is a key escape site.
Structural comparisons show that XGv347 is similar to a neutralizing antibody (A23-58.1) that is effective against several strains of the new coronavirus variant and similar to the epitope (antibody binding site) targeted by another neutralizing antibody (S2K146). Notably, S2K146 is effective against other B coronavirus tributary B (i.e., the subgenus Sarbecovirus, a group of viral clades to which the coronavirus belongs).
Further experiments in this study also showed that representative broad-spectrum neutralizing antibody treatments were highly protective of beta and Omiljunn variants of mice.
Protective effect of neutral antibody therapy on infection of beta variants and Omiljung variants in mice.
The research team believes that the study proves that the three-dose vaccination regimen is justified in the current pandemic. At the same time, antibodies that identify and identify the same regional epitope are classified, and different types of antibodies can form cocktail therapies for the prevention and treatment of current epidemic strains and possible new strains in the future, or to help develop a universal vaccine strategy against branch B of the novel coronavirus.
Original link: https://www.nature.com/articles/s41586-022-04466-x