Humanized antibody of novel coronavirus rare broad-spectrum epitope and application thereof

Abstract

The invention relates to a novel human antibody of a coronavirus rare broad-spectrum epitope and application thereof. A model of successive screening of prototype strain RBD and Beta strain RBD antigens is utilized, conservative target sites are rapidly focused, and the fully human antibody IMCAS-364 which is combined with different epitopes of the RBD and can realize broad-spectrum neutralization of VOC is successfully separated. The affinity of the strain to a prototype strain, Alpha, Beta, Delta and Omicron reaches an nM level. A known epitope antibody competition experiment proves that IMCAS-364 is combined with a rare target position on the inner side surface of RBD and does not compete with a receptor, and the antibody combined with the target position has the characteristic that the antibody does not compete with ACE2 but can neutralize a new crown for the first time. The IMCAS-364 has the potential of being paired with an antibody which plays a neutralizing role through receptor blocking, has the capability affinity of being combined with atypical pneumovirus at nM level, and can be used for developing a neutralizing antibody of a general SARS coronavirus.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a human antibody of a rare broad-spectrum epitope of a novel coronavirus and an application thereof. Background technique [0002] Screening broad-spectrum high neutralizing active antibodies against the novel coronavirus is of great practical significance for clinical prevention and treatment. [0003] After the outbreak of the new crown, all human beings have built the largest pre-existing immunity through vaccines. However, as the virus continues to spread in the population, various mutations have brought great pressure to the global vaccine immune defense. At present, the emergence of Omicron not only surpasses the multiple vaccines. As for the immune defense line, only S309 of the 8 antibodies on the world’s market can continue to resist, and Omicron has the possibility of cross-species transmission and infection of rodents such as mice. It is worthy of vigi...

AI Technical Summary

Problems solved by technology

[0004]However, the current research techniques are limited. The 2988 antibody produced by sequencing the peripheral blood cells of recovered patients around the world is mainly aimed at immunodominant epitopes that lack the ability to resist mutations , there is little broad-spectrum neutralization ability for conserved epitopes, and several top-level journal articles have paid attention to this problem

From the perspective of evolutionary selection, only weak immunogenicity of conserved epitopes can adapt to host immune confrontation. In view of the low immunogenicity of conserved sites, in the study of influenza broad-spectrum antibodies, scientists further focused on different antigens through immunofocus, The strategy of continuous immunization improves the "effective mobilization of antibodies" and then obtains broad-spectrum antibodies. For example, the S309 antibody was obtained from a patient who had been infected with atypical pneumonia virus (SARS-CoV) for 10 years in vitro using the SARS2 target protein, but Not only are there very few such volunteers, but there is still no correlation conclusion to achieve broad-spectrum at the level of sarbecoviruses, which must be effective against SARS2 new mutations. Only from the perspective of Omicron, it includes S2H97, 2-36, MW06 and other pan- sarbecovirus star antibody appears to lose efficacy

What's more troublesome is that the SARS2 outbreak was not long, and the probability of the same person being infected with different VOC virus strains successively or the possibility of alternately immunizing the same person with different VOC vaccines is extremely small, which drives researchers to find another way to discover this weak immunogen. Broad-spectrum antibodies against sexually rare targets

Images