Ab&B Bio-Tech CO.,LTD.JS has developed the world's first broad-spectrum mRNA vaccine against smallpox virus
- Time of issue:2023-05-08
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[概述]Since May 2022, the global epidemic of monkeypox virus has drawn public attention to the threat of human-to-human transmission of zoonotic diseases1, and the World Health Organization urgently declare
Ab&B Bio-Tech CO.,LTD.JS has developed the world's first broad-spectrum mRNA vaccine against smallpox virus
[概述]Since May 2022, the global epidemic of monkeypox virus has drawn public attention to the threat of human-to-human transmission of zoonotic diseases1, and the World Health Organization urgently declare
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- Time of issue:2023-05-08
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Since May 2022, the global epidemic of monkeypox virus has drawn public attention to the threat of human-to-human transmission of zoonotic diseases1, and the World Health Organization urgently declared the monkeypox epidemic as a public health event of international concern in July 2022. Academia and pharmaceutical companies are also actively proposing various prevention and control strategies, including the rapid development of vaccines.
On April 26, 2023, Dr. Xiong Yelin (Vice President) and Dr. Liu Zhihua (Project Director) of Yither biotech (Shanghai) Co., Ltd (Yither Bio), a wholly-owned subsidiary of Ab&B Bio-Tech Co.,Ltd（Ab&B Bio）, announced their proposal on bioRxiv. The company's research progress on Orthopox virus broad-spectrum mRNA vaccine "A Quadrivalent mRNA immunization elicits potent immune responses against vaccine and monkeypox viral antigens – a step closer to a broad orthopoxvirus vaccine" 2.
The company's R&D team found through preliminary research that, in addition to monkeypox virus, other poxviruses including vaccinia and camelpox virus are also contagious and pathogenic to humans, and there is smallpox as a biological terrorist or accidental escape from the laboratory. risk of recurrence.
Vaccinia virus, smallpox virus, monkeypox virus, camelpox virus, sheeppox virus and vaccinia virus are similar in morphology and have a certain antigenic correlation3. Among them, A27, A33, B5 and L1 and their related homologous proteins involved in the adsorption, binding and cell-to-cell transmission of virus-infected cells are highly conserved in related orthopoxviruses, which is also the great achievement of live attenuated poxvirus vaccines in preventing smallpox in the last century. Basics of Successful Immunology 4-7. Antibody studies have shown that A27, A33, B5 and L1 have a large number of broad-spectrum neutralizing epitopes8, suggesting that these antigens can be candidate antigens for broad-spectrum vaccines.
Based on the above basic understanding of pathogenic biology and vaccinology, the team chose to design vaccinia virus surface antigens A27, A33, B5, and L1 in series to form a single mRNA molecule, and developed the first in the world through the mRNA-LNP delivery platform A 4-valent broad-spectrum mRNA vaccine candidate (mRNA-ALAB) against Orthopoxvirus spp.
Figure 1, mRNA-ALAB design and in vitro expression verification
The 4-valent mRNA transfected HEK293T cells can specifically express four antigen molecules (Figure 1); mRNA-ALAB can induce strong antigen-specific binding antibody and neutralizing antibody responses in mice through intramuscular injection (Figure 1). 2), and excellent cellular immune response (Figure 3).
Figure 2. Humoral immune response induced by mRNA-ALAB vaccine
Figure 3. Cellular immune response induced by mRNA-ALAB vaccine
At the same time, the antibodies induced by the vaccine can strongly cross-link with homologous antigens of monkeypox virus (A29, M1, A35 and B6) (Figure 4), which indicates that the mRNA-ALAB vaccine can be used as a vaccine against pox including monkeypox virus Potential vaccine candidates for viral infections.
Figure 4. Cross-reaction of mRNA-ALAB vaccine immune sera with monkeypox antigen
While inducing a strong immune response, the mRNA vaccine did not cause any safety concerns in animal experiments, avoiding the severe side effects often caused by traditional attenuated poxvirus vaccines; in terms of molecular design, compared with multiple mRNA molecules The company has developed an original design for the delivery of multiple antigens by a single mRNA molecule, which greatly simplifies the process, shortens the development cycle, and has a high production cost advantage; in order to deal with large-scale outbreaks, it provides a feasible vaccine design ideas.
In the future, the company's R&D team will conduct more research on the broad-spectrum and functionality of the vaccine.
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