In a recent study published on the medRxiv * prepress server, researchers evaluated the neutralizing capacity of sera from patients with coronavirus disease 2019 (COVID-19).
Study: Innovative pre-Omicron vaccine infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than the first infection. Image credit: Lightspring / Shutterstock
The causal pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved throughout the pandemic, emerging as mutant variants with improved characteristics. SARS-CoV-2 variants that are highly transmissible or immunoevasive easily outperform previously dominant strains. Vaccines such as Pfizer’s BNT162b2, Moderna’s mRNA-1273, Janssen’s Ad.26COV2.S, and AstraZeneca’s ChAdOx1 are effective in protecting against serious disease.
However, protection against infection is deficient, especially for the Delta and Omicron variants of SARS-CoV-2. The protection conferred by previous infection with pre-Omicron (VOC) concern variants against the Omicron variant is debatable. Some reports indicated that innovative infection with the Omicron BA.1 variant induces neutralizing antibodies (nAbs) against previous BA.1 and VOCs; however, these nAbs exhibit little cross-neutralization activity against Omicron underlines.
Omicron infection in unvaccinated individuals causes nAbs with insufficient neutralization against all VOCs. The widespread spread of SARS-CoV-2 Omicron ensures a better understanding of sensitivity to neutralization by vaccination or infection-induced antibodies.
About the study
In the present study, the researchers compared the neutralization of Omicron BA.1 by serum of unvaccinated convalescents and those who had innovative vaccine infections. Serum samples were obtained from 70 convalescent individuals (hereinafter convalescent sera) infected with the ancestral B.1 strain and from 16 vaccinated subjects (BTI beings) who experienced innovative infection with VOC Gamma or Delta. The severity of COVID-19 was classified into mild / asymptomatic, moderate, and severe disease.
The research team isolated the D614G strain and the Gamma, Delta, or Omicron VOCs from patients ’leftover nasopharyngeal swabs. They added a residual swab preservation medium to Vero E6 cells and visually monitored the cytopathic effect (CPE). The viral supernatant was then used to reinfect Vero E6 cells (step 2) to establish a viral stock. The SARS-CoV-2 variants of the leftover swabs were sequenced by next-generation sequencing (NGS) and the ear gene (S) was sequenced again after step 2 to verify sequence conservation. . Finally, they performed a live virus neutralization test.
Discoveries
Most convalescent serum samples were collected from patients with moderate or severe disease. Maximum mean inhibitory concentration (IC50) values of convalescent sera showed a wide range of neutralizing activity against variants B.1, Gamma, and Delta with comparable geometric means.
All but one of the convalescent samples did not neutralize Omicron at the highest serum concentration tested.
Samples with low / no neutralization activity against one variant often had a higher neutralization against another variant. The convalescent sera of patients with moderate COVID-19 had the highest neutralizing activity against B.1 and VOC. They then measured antibodies targeting the S protein, its receptor-binding (RBD) and N-terminal (NTD) domains, and the nucleocapsid (N) protein. All patients had detected levels of anti-N, anti-S, and anti-RBD antibodies.
Anti-NTD antibodies were inferior / undetectable in some patients with severe disease. The authors observed a moderate correlation between neutralizing activity and antibody levels. Consistently, sera from moderate patients with COVID-19 showed higher antibodies against S, RBD, NTD, and N than in severe cases.
BTI sera were collected from two infected patients with Gamma variant and 14 cases of Delta variant. The mean time from complete vaccination was 3.06 months. BTI sera were stratified into non / slightly neutralizing and highly neutralizing sera (eight samples in each category). Five non-neutralizing or slightly neutralizing serums showed no neutralization against strain B.1 at the highest serum concentration tested.
They observed that BTI serum samples that neutralized strain B.1 at dilutions ≥ 1:80 retained neutralization against the corresponding infectious VOCs or exhibited higher neutralization against VOCs. In contrast, most samples, which were unable to neutralize strain B.1, had no neutralizing activity against the infecting variant. More than half of BTI cases demonstrated nAbs versus Gamma or Delta VOC. Thus, serum samples had better cross-neutralization activity against the Delta variant than strain B.1.
All BTI sera showed a substantial decrease in neutralization against the Omicron BA.1 variant. However, eight samples with high neutralizing activity against B.1. Gamma or Delta retained partial neutralization against BA.1. Anti-S, anti-RBD, and anti-NTD antibody levels were higher except for a BTI sample. Neutralizing activity against strain B.1 correlated well with antibodies against RBD, NTD, and protein S, but less so with anti-N antibodies.
Conclusion
In summary, BTI sera showed a higher neutralizing capacity against the SARS-CoV-2 B.1 strain and VOCs, including Omicron BA.1, than convalescent sera. Of the eight BTI sera that neutralized B.1 and VOC, six samples partially neutralized BA.1. This revealed that innovative infection with a pre-Omicron variant elicited antibodies that could cross-neutralize the Omicron BA.1 variant.
In particular, higher neutralization was achieved with lower antibodies against S, N, RBD, and NTD in BTI sera relative to convalescent sera, implying greater neutralization efficiency with antibody titers. lower, perhaps due to improved antibody affinity. These findings highlighted the qualitative differences in antibodies between unvaccinated convalescent and vaccinated convalescent individuals and suggested that innovative infection could increase the immune response and induce cross-neutralizing antibodies.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.