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Since the beginning of the pandemic, 12.
7 billion doses of COVID vaccines
have been administered worldwide.
However, the current vaccination is mainly to prevent severe disease and cannot effectively prevent the infection and spread
of the new coronavirus.
The virus continues to circulate
in hundreds of thousands of new infections worldwide every day.
In addition, with the continuous mutation of the new coronavirus and the emergence of immune escape strains, the protection of existing vaccines and antibodies is also declining
.
Therefore, in response to the global epidemic of SARS-CoV-2, there is an urgent need to develop an effective mucosal vaccine to prevent infection and transmission
of the new coronavirus and emerging mutant strains.
On October 11, 2022, the team of Yan Huimin of the Shanghai Public Health Clinical Center (affiliated to Fudan University), the team of Shi Zhengli of the Wuhan Institute of Virology, Chinese Academy of Sciences, and the team of Chen Yaoqing of the School of Public Health of Sun Yat-sen University (Shenzhen) worked together to develop a broad-spectrum and efficient new crown sub-nasal mucosal vaccine
.
"A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern" was published in the internationally renowned academic journal Cellular & Molecular Immunology
。 The researchers used a novel protein skeleton design to integrate multiple novel coronavirus receptor binding domains (RBDs) into a single recombinant protein and screen for a highly efficient eukaryotically expressed and soluble and stable immunogen 3Ro-NC
containing RBD trisomy .
Figure 1.
The 3Ro-NC recombinant protein molecule of the three-part design of RBD contains a Delta strain RBD located in the middle and two Omicron BA.
1 strain RBDs
located at both ends.
3Ro-NC showed superior immunogenicity
in BALB/c mice.
3Ro-NC induces high titers of RBD-specific IgG antibodies in serum by intramuscular injection; And it can effectively neutralize all the current SARS-CoV-2 mutant pseudoviruses, especially the neutralizing activity of the currently circulating Omicron strain
.
Figure 2.
RBD trisomy high immunogenicity Based on the design of RBD trisomy immunogen and efficient protein expression, the research team deeply explored and evaluated the combination dosage form of trisomy RBD (3Ro-NC) and recombinant flagellin protein adjuvant (KFD) and the strategy
of nasal mucosal immunity.
The experimental results showed that 3Ro-NC mixed with KFD triple nasal immunisation (3Ro-NC+KFDi.
n) could induce ACE2 transgenic mice to produce high-titer RBD-specific IgG antibodies against different new crown mutant strains, and the corresponding antibody titer was higher than the antibody titer
induced by 3Ro-NC plus aluminum adjuvant intramuscular injection immunization (3Ro-NC+ALi.
m).
。 Notably, only nasal immunisation (3Ro-NC+KFDi.
n) can induce a potent RBD-specific IgA antibody response
in saliva, nasal cavity, and vaginal lavage fluids.
Further nasal challenge was carried out in the tertiary safety laboratory with the Omicron variant strain in these immunized ACE2 transgenic mice, and the results showed that compared with the non-immunized control mice, the virus copy number in the lung tissue of mice immunized with nasal drip immunization (3Ro-NC+KFDi.
n) was reduced by 85.
7 times, which was comparable
to that of mice immunized with inactivated vaccine.
Of particular note is that only mice immunized by nasal drops (3Ro-NC+KFDi.
n) had a 13.
6-fold
reduction in viral copy number in turbinate bone tissue.
In addition, there were no observable inflammatory pathology
in the lungs in nasal immunized (3Ro-NC+KFDi.
n) mice compared to inducing significant inflammatory cell infiltration in the lungs with inactivated vaccines.
Correlation analysis showed that a decrease in viral copy number in lung tissue was associated
with a specific IgG response in serum.
However, the viral load in nasal tissues was significantly negatively correlated with the response of mucosal secretory IgA antibodies, indicating that the mucosal IgA antibody response played a role
in preventing virus invasion and inhibiting initial infection in the mucosa of the upper respiratory tract.
Figure 3.
The combination of RBD trisomy and flagellin adjuvant can induce a significant specific mucosal immune response, and effectively control the replication and value-added of the virus in the nasal cavityThe overall study shows that the new immunogen of RBD trisomy (3Ro-NC) combined with recombinant flagellin protein adjuvant (KFD) can simultaneously induce a highly effective protective system immune response and mucosal immune response through nasal mucosal inoculation.
At the same time, it provides specific anti-SARS-CoV-2 virus Omicron variant infection and potential transmission for the upper respiratory tract and lower respiratory tract, becoming a broad-spectrum and highly effective anti-new crown submucosal vaccine
with great clinical application prospects.
Yan Huimin, researcher of Shanghai (Fudan University) Public Health Clinical Center, researcher Shi Zhengli of Wuhan Institute of Virology, and Professor Chen Yaoqing, School of Public Health, Sun Yat-sen University (Shenzhen) are the co-corresponding authors of the paper, and Dr.
Yang Jingyi, Dr.
Liu Meiqin and doctoral student Lin Liu are the co-first authors
.
The research has been supported
by the National Natural Science Foundation of China, the National Key R&D Program of the Ministry of Science and Technology, the Shenzhen Peacock Talent Team, and the Shenzhen Outstanding Youth Fund.
Links to papers: style="margin-right: auto;margin-left: auto;outline: 0px;width: 30px;display: inline-block;">
7 billion doses of COVID vaccines
have been administered worldwide.
However, the current vaccination is mainly to prevent severe disease and cannot effectively prevent the infection and spread
of the new coronavirus.
The virus continues to circulate
in hundreds of thousands of new infections worldwide every day.
In addition, with the continuous mutation of the new coronavirus and the emergence of immune escape strains, the protection of existing vaccines and antibodies is also declining
.
Therefore, in response to the global epidemic of SARS-CoV-2, there is an urgent need to develop an effective mucosal vaccine to prevent infection and transmission
of the new coronavirus and emerging mutant strains.
On October 11, 2022, the team of Yan Huimin of the Shanghai Public Health Clinical Center (affiliated to Fudan University), the team of Shi Zhengli of the Wuhan Institute of Virology, Chinese Academy of Sciences, and the team of Chen Yaoqing of the School of Public Health of Sun Yat-sen University (Shenzhen) worked together to develop a broad-spectrum and efficient new crown sub-nasal mucosal vaccine
.
"A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern" was published in the internationally renowned academic journal Cellular & Molecular Immunology
。 The researchers used a novel protein skeleton design to integrate multiple novel coronavirus receptor binding domains (RBDs) into a single recombinant protein and screen for a highly efficient eukaryotically expressed and soluble and stable immunogen 3Ro-NC
containing RBD trisomy .
Figure 1.
The 3Ro-NC recombinant protein molecule of the three-part design of RBD contains a Delta strain RBD located in the middle and two Omicron BA.
1 strain RBDs
located at both ends.
3Ro-NC showed superior immunogenicity
in BALB/c mice.
3Ro-NC induces high titers of RBD-specific IgG antibodies in serum by intramuscular injection; And it can effectively neutralize all the current SARS-CoV-2 mutant pseudoviruses, especially the neutralizing activity of the currently circulating Omicron strain
.
Figure 2.
RBD trisomy high immunogenicity Based on the design of RBD trisomy immunogen and efficient protein expression, the research team deeply explored and evaluated the combination dosage form of trisomy RBD (3Ro-NC) and recombinant flagellin protein adjuvant (KFD) and the strategy
of nasal mucosal immunity.
The experimental results showed that 3Ro-NC mixed with KFD triple nasal immunisation (3Ro-NC+KFDi.
n) could induce ACE2 transgenic mice to produce high-titer RBD-specific IgG antibodies against different new crown mutant strains, and the corresponding antibody titer was higher than the antibody titer
induced by 3Ro-NC plus aluminum adjuvant intramuscular injection immunization (3Ro-NC+ALi.
m).
。 Notably, only nasal immunisation (3Ro-NC+KFDi.
n) can induce a potent RBD-specific IgA antibody response
in saliva, nasal cavity, and vaginal lavage fluids.
Further nasal challenge was carried out in the tertiary safety laboratory with the Omicron variant strain in these immunized ACE2 transgenic mice, and the results showed that compared with the non-immunized control mice, the virus copy number in the lung tissue of mice immunized with nasal drip immunization (3Ro-NC+KFDi.
n) was reduced by 85.
7 times, which was comparable
to that of mice immunized with inactivated vaccine.
Of particular note is that only mice immunized by nasal drops (3Ro-NC+KFDi.
n) had a 13.
6-fold
reduction in viral copy number in turbinate bone tissue.
In addition, there were no observable inflammatory pathology
in the lungs in nasal immunized (3Ro-NC+KFDi.
n) mice compared to inducing significant inflammatory cell infiltration in the lungs with inactivated vaccines.
Correlation analysis showed that a decrease in viral copy number in lung tissue was associated
with a specific IgG response in serum.
However, the viral load in nasal tissues was significantly negatively correlated with the response of mucosal secretory IgA antibodies, indicating that the mucosal IgA antibody response played a role
in preventing virus invasion and inhibiting initial infection in the mucosa of the upper respiratory tract.
Figure 3.
The combination of RBD trisomy and flagellin adjuvant can induce a significant specific mucosal immune response, and effectively control the replication and value-added of the virus in the nasal cavityThe overall study shows that the new immunogen of RBD trisomy (3Ro-NC) combined with recombinant flagellin protein adjuvant (KFD) can simultaneously induce a highly effective protective system immune response and mucosal immune response through nasal mucosal inoculation.
At the same time, it provides specific anti-SARS-CoV-2 virus Omicron variant infection and potential transmission for the upper respiratory tract and lower respiratory tract, becoming a broad-spectrum and highly effective anti-new crown submucosal vaccine
with great clinical application prospects.
Yan Huimin, researcher of Shanghai (Fudan University) Public Health Clinical Center, researcher Shi Zhengli of Wuhan Institute of Virology, and Professor Chen Yaoqing, School of Public Health, Sun Yat-sen University (Shenzhen) are the co-corresponding authors of the paper, and Dr.
Yang Jingyi, Dr.
Liu Meiqin and doctoral student Lin Liu are the co-first authors
.
The research has been supported
by the National Natural Science Foundation of China, the National Key R&D Program of the Ministry of Science and Technology, the Shenzhen Peacock Talent Team, and the Shenzhen Outstanding Youth Fund.
Links to papers: style="margin-right: auto;margin-left: auto;outline: 0px;width: 30px;display: inline-block;">
—END—
The content is 【iNature】
