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This article is the original of Translational Medicine Network, please indicate the source for reprinting
Written by Jevin
Summary: The new coronavirus SARS-CoV-2 continues to accumulate mutations, and the immune escape ability is getting stronger and stronger, resulting in breakthrough infections
that people still have after vaccination.
How to predict the evolutionary trajectory of the virus in advance has become a difficult problem
that researchers need to overcome in the design of the next generation of vaccines.
On January 4, 2023, Lanke and Xu Ke of Wuhan University jointly published a research paper online in the journal Science Translational Medicine, which defined the infectivity and immune evasion ability of 54 SARS-CoV-2 pseudoviruses (including 45 single mutations, 8 variants and WT strains), and analyzed the evolutionary route
of SARS-CoV-2 S protein 。 Through phylogenetic analysis of 2675 S proteins, the study resulted in a universal Span vaccine with the most frequent mutations that can have a broadly effective neutralizing effect on all variants of concern and variants of concern to date
.
style="box-sizing: border-box;" _msthash="251139" _msttexthash="1376349">The evolutionary path of the new coronavirus
01
The study reported for the first time the evolutionary path of the new coronavirus, finding that mutations in the virus spike (S) protein in virus isolates that survived in the human population were not completely random, but evolved
along three directional pathways.
One path is where mutations lead to high cellular infectivity while maintaining weak immune evasion (e.
g.
, Delta and Lambda strains), the second path is mutation leading to low cellular infectivity while acquiring strong immune evasion (e.
g.
, gamma strains), and the third pathway has a relatively small number of variants that increase both cellular infectivity and immune evasion (e.
g.
, beta strains) (Figure 2).
This shows that in most cases, the regulation of function by mutations in S protein needs to be coordinated, rather than simply enhanced or weakened
.
Research process
02
Because the new coronavirus has different evolutionary paths, vaccines with a single strain cannot effectively protect populations against other variants on different evolutionary paths
.
In order to cope with the multiple evolutionary paths of the new crown strain and avoid antigen drift and mutation of the evolutionary strain, the Wuhan University research team adopted a new design strategy to complete the sequence design
of the broad-spectrum vaccine immunogen Span.
The researchers analyzed the homology of 2675 protein sequences in the NCBI database to design the Span immunogen
.
Mouse experiments demonstrated that mice vaccinated with a booster shot of the Span vaccine had complete protection
against fatal infection with the Omicron variant.
It further proves the importance and feasibility of
broad-spectrum vaccines against new coronavirus antigen drift.
Through the clustering algorithm, the Wuhan team screened out the most common mutations in five different clades, namely D614G, del69-70, del144, N501Y and P681H
.
And complete the full coverage
of Span protein antigen to high-frequency mutation points.
By including high-frequency mutation sites, the Span vaccine protects vaccinated populations from highly contagious variants
.
In contrast, the high immune escape variant is completely covered
by Span.
Research significance
03
Span antigen not only improves protection against covered mutations, but also improves neutralization activity
against uncovered mutations.
Compared to the SWT vaccine, the Span vaccine showed a wider range of neutralizing activity
for all 10 variants.
Therefore, the pan-novel coronavirus S protein immunogen (Span) designed based on the common evolutionary mutation of the new crown is expected to become a broad-spectrum vaccine
candidate for the prevention of existing and potential future epidemic strains of the new coronavirus.
This work conducted a proof-of-concept of this innovative broad-spectrum vaccine design concept with excellent results
.
Resources:
style="white-space: normal;box-sizing: border-box;">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.
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