NRI Pengfei Wang and Shibo Jiang, Fudan University: Broad-spectrum neutralizing antibodies against SARS-CoV-2 and other HCoV

Recently, Pengfei Wang, a young researcher (corresponding author) at the School of Life Sciences of Fudan University and Professor Jiang Shibo (corresponding author) of the School of Basic Medicine of Fudan University, published a review article on broad-spectrum neutralizing antibodies (bnAbs) against SARS-CoV-2 and others infected with coronavirus (HCoV) in Nature Reviews Immunology (IF: 108.
555), an authoritative journal of immunology antibodies to SARS-CoV-2 and other human coronaviruses” （doi: 10.
1038/s41577-022-00784-3）
。

This review systematically sorts out the various neutralizing antibodies developed by researchers against the new crown virus (SARS-CoV-2), and by comparing the differences between neutralizing antibodies in different binding epitopes, the authors give some evaluation indicators for the selection of neutralizing antibodies as the prevention or treatment of COVID-19, and make suggestions for follow-up research directions such as antibody combination and modification of antibodies; In addition, by analyzing the neutralizing antibody characteristics and using reverse vaccine methods, the authors also propose research and development strategies
for the next generation of broad-spectrum anti-coronavirus vaccines.

Since the emergence of COVID-19 in 2019, multiple variants have led a wave of outbreaks in parts of the world, causing millions of deaths
.
And new variants carry specific mutations that are more likely to escape the original immune barrier, leading to breakthrough infections; Some neutralizing antibodies (nAbs) that have been approved for clinical practice or are ready for clinical trials have also been shown to have their neutralizing effects resisted by some mutant strains, causing these neutralizing antibodies to lose their original protective effects
.

The spike(S) protein is a characteristic protein of coronaviruses that is primarily responsible for recognizing and binding to the corresponding receptors on the surface of the host cell, helping the virus enter the host cell
.
The neutralizing antibodies against the new crown virus are basically targeting the S protein, especially the RBD (receptor-binding domain) region
in the S protein.

In this article, the authors selected the four most common antibody epitopes on the S protein: NTD (N-terminal domain), RBD (receptor binding domain), SH (stem helix), FP (fusion peptide), by looking for neutralizing antibody data in published articles, sorting according to antibody binding epitopes, in the body and supplementary material table, Detailed information on more than 60 monoclonal antibodies (mAbs) was summarized (including: identification sites, neutralization mechanisms, broad-spectrum degree and neutralization efficiency)

By comparing the neutralizing antibody features of different epitopes, the authors found that those antibodies against class 1 & class 2 in NTD and RBD were prone to immune evasion of new viruses due to the high frequency of identified sequence mutations; Antibodies that recognize SH and FP, due to their highly conserved sequence, tend to have excellent broad-spectrum anti-coronavirus profile
.
However, the authors also point out that when screening neutralizing antibodies for use as drugs to prevent or treat COVID-19, it is necessary to balance the neutralization efficiency and broad-spectrum of antibodies; Either neutralizing antibodies with different epitopes/using bispecific antibodies or multispecific antibodies in the hope of creating synergistic effects
.
In addition, the authors also mention that for existing antibodies, new antibodies with better performance can be produced by sequence optimization or structural optimization
.

Finally, for vaccine design, the author gives two guidance suggestions for the next generation of anti-coronavirus vaccine design from the perspective of protecting the broad spectrum: First, vaccines containing S protein (complete or partial) antigens of a variety of coronaviruses can be designed and immunized, due to the sequential differences in the S protein (complete or partial) antigens contained in different coronaviruses, mixing these S proteins will increase the probability that the body's immune system produces / enhances immune responses to those conservative epitopes, and obtains the corresponding memory cells, Plays a broad-spectrum protective role; The second is to select conservative immune epitopes in viral surface proteins to design vaccines, and use high-efficiency adjuvants, such as CF501, a new adjuvant based on STING agonists, to induce efficient and broad-spectrum neutralizing antibodies and T cell immune response and anti-infection protection in
the immune host.

Yanjia Chen and Dr.
Xiaoyu Zhao from the School of Life Sciences of Fudan University, Dr.
Zhou Hao from the School of Medicine of New York University (now Chengdu University of Traditional Chinese Medicine) are the co-first authors of the paper, and Professor Huanzhang Zhu of the School of Life Sciences of Fudan University participated in the writing
of this review.

For original text/project cooperation, please contact Pengfei Wang Young Researcher, Email: pengfei_wang@fudan.
edu.
cn