New study reveals neutralization of SARS-CoV-2 variants and protection against omicron by new mAbs

In a recent study posted on medrex sib*In a preprint server, researchers will explore the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and the ability of vaccine-induced antibodies and monoclonal antibodies (mAbs) to I appreciate the peace.

Background

The continued emergence of SARS-CoV-2 VOCs around the world has raised health concerns, prompting efforts to immunize against coronavirus disease 2019 (COVID-19) and improved anti-viral drugs. The need to develop SARS-CoV-2 therapeutics is justified. Comparative assessment of humoral immune responses and neutralization to SARS-CoV-2 VOCs may help broaden the therapeutic landscape for COVID-19.

About research

In this study, investigators used previously developed and validated serum samples to evaluate serum samples from individuals vaccinated with COVID-19 vaccines (such as messenger ribonucleic acid (mRNA)-1273, Ad26.COV2.S or BNT162b2). used a live virus neutralization assay. History of SARS-CoV-2 infection with an ancestral strain or Omicron subvariant. In addition, neutralization of SARS-CoV-2 variants by double-dose vaccine-induced antibodies was evaluated.

SARS-CoV-2 VOCs are Nasopharyngeal swab COVID-19 patient samples and all VOC isolates by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis were ancestral to SARS-CoV-2 strains, namely SARS-CoV-2/WA-1 and SARS. Was analyzed developmentally-CoV-2/Wuhan-Hu-1 strain as a reference.

Plaque reduction neutralization titers (PRNT) analyzes were performed and neutralization difference (ND) values ​​were calculated for vaccination from 8 and 7 sera double vaccinated with mRNA-1273 and BNT162b2, respectively. We evaluated SARS-CoV-2 VOC neutralization efficacy and COVID-19 convalescent patients (n=13). Additionally, the effect of booster vaccination on SARS-CoV-2 VOC neutralization was evaluated.

Omicrons detected in Seattle using the SARS-CoV-2 Spike (S) Gene Targeted Disorder (SGTF) PCR assay were sequenced by Whole Genome Sequencing (WGS) analysis. SARS-CoV-2/WA-1 strain.

In addition, we performed mAb screening to identify potential mAbs. Effectiveness Against Omicron, mAbs were evaluated for S RBD-ACE2 binding by an enzyme-linked immunosorbent assay (ELISA). In addition, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2)-expressing-A549 cells.

result

Neutralization analysis across all VOCs showed that the prime-boost regimen provided immunoprotection against Omicron BA.1 (ND between prime and booster vaccination was 20 vs. 3.5), and the booster dose enhanced neutralization of ancestral strains. shown to significantly enhance the neutralization of Omicron BA.1 (ND 54 vs 9.4).

The booster dose increased Omicron BA.1 neutralization by 50-fold compared to the primary vaccination dose. Although recovery >5 months did not effectively protect against Omicron BA.1, SARS-CoV-2 infection and post-recovery COVID-19 vaccination were potent SARS, except for Omicron BA.1. -provided CoV-2 neutralization.

There was no significant difference between BNT162b2 and mRNA-1273 vaccines in neutralizing SARS-CoV-2 VOCs. In contrast, convalescent sera from an unvaccinated individual showed significantly lower cross-variant neutralization titers than the COVID-19 vaccine (compared to her vaccinated COVID-19 convalescent patient). Her ND range was between his 2.8 and 3.5).

The Seattle Omicron VOC was similar to the Omicron BA.1. However, the S1265I mutation and a deletion of amino acids (aa) 105 to 107 of nonstructural proteins 3 and 6, respectively, were detected in the Seattle Omicron variant. In addition, the Seattle Omicron contains the R346K mutation and mutations in SARS-CoV-2 (aa 68-69 sites, aa 142-144 sites, aa 211 sites) and SARS-CoV-nucleocapsid (NP) protein-encoding aa 30-47. deletion. Compared to Seattle Omicron BA.1, Omicron BA.2 exhibited additional S protein mutations, with 20 aa differences between BA.1 S and Omicron BA.2 S.

Infection and viral growth analyzes showed significantly slower growth of BA.1 than the SARS-CoV-2/WA-1 strain, with a significantly smaller peak, but more growth in HSAEC than in HBEC. showed. Four mAbs were identified that neutralized the ancestral strain and Delta VOCs, of which mAb 297 neutralized the ancestral strain and Delta plus BA.1 and BA.1 at levels comparable to ancestral strain neutralization by the REGN10987/10933 mAb cocktail. 2 effectively neutralized.

Overall, the study results suggest that immune-evading Omicron VOCs generate a blunted neutralizing humoral immune response compared to ancestral strains and booster vaccination and administration of mAbs to enhance immune protection against SARS-CoV-2. has shown that it supports

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .