In a recent study published in Science, researchers evaluated a panel of seven vaccines of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently available worldwide and in the United States (US) and acquired immunity to through the previous infection against all Omicron subvariants. .
Study: Omicron ear function and neutralizing activity caused by a complete panel of vaccines. Image credit: BaLL LunLa / Shutterstock
Fund
The latest variant of concern (VOC) of the SARS-CoV-2 Omicron, with its potential to evade host infection control strategies, is more apt and transmissible than its predecessors. It has evolved into several underlinings, and the most dangerous Omicron BA.5 subvariant will soon dominate globally replacing other variants. Due to the increase in innovative infections and improved transmissibility of Omicron BA.5., The U.S. government is considering recommending a second dose of booster vaccination for adults under 50 years of age.
SARS-CoV-2 vaccines use tip (S) glycoprotein (sometimes just the receptor-binding domain (RBD)) or virus (inactivated) and a number of delivery technologies. Although Omicron subvariants have severely decreased the protective immunity induced by the primary vaccine series or previous infection, preliminary studies have pointed to the potential of booster vaccination to obtain neutralizing antibodies against Omicron subvariants.
About the study
In the present study, the researchers first examined the functional impact of mutations on S proteins in Omicron subvariants, which give it a crown-like appearance and allow fusion with crucial host cells. to establish an infection. They then evaluated the neutralizing activity caused by vaccines or previous infection against all Omicron subvariants. They created the vesicular stomatitis virus (VSV) pseudotyped with the SARS-CoV-2 Wuhan-Hu-1 S that harbors the mutations D614G, BA.2.12.1, BA.1, BA.2 or BA.4 / 5.
In addition, the researchers used VeroE6 cells expressing serine transmembrane protease 2 (TMPRSS2) to propagate VSV in the presence of vaccinated or convalescent plasma, obtained early in the pandemic. They determined a geometric mean plasma neutralizing titer (GMT) of neutralizing activity against any of the four Omicron sublinings tested. The researchers also evaluated neutralizing antibodies to the Omicron subvariant caused by the mRNA-1273, BNT162b2, Ad26.COV2, AZD1222, NVX-CoV2373, Sputnik V, and BBIBP-CorV vaccines. The primary vaccine series of six vaccines consisted of two doses, except Ad26.COV2.
They measured and compared the benefits of vaccine enhancements on plasma neutralizing activity against the ancestral SARS-CoV-2 virus and Omicron subvariants. In addition, they evaluated and compared the benefits of homologous or heterologous vaccine enhancements.
Study results
The results of biolayer interferometry (BLI) and surface plasmon resonance (SPR) showed that the binding affinity to the angiotensin converting enzyme 2 (ACE2) of Omicron BA.4 / 5 RBD it was the largest of all tested RBDs. It bound ACE2 more than six times stronger than the ancestral strain SARS-CoV-2 Wuhan-Hu1. In contrast, all Omicron subvariants were slower than Wuhan-Hu-1 and Delta VOC when fused to the host cell membrane, a phenomenon called fusogenicity. The researchers hypothesized that a more robust ACE2 binding capacity compensated for the weaker fusogenicity of Omicron.
Only five serum samples from the 24 early pandemic samples had detectable neutralizing activity against any of the Omicron underlinings tested, and even their response was weak. Based on the magnitude of evasion of polyclonal serum neutralizing antibody responses for Omicron underlinings in vaccinated individuals, the authors confirmed that the Omicron BA.5 subvariant would be the elusive variant of SARS-CoV-2. more immune so far. In addition, the type of vaccine had little effect on the neutralizing antibody responses elicited against Omicron subvariants. Compared with BA.2 and BA.2.12.1, the authors observed a consistently higher magnitude of neutralizing antibody responses for the BA.1 and BA.4 subvariants.
After primary vaccination, three subjects had detectable neutralizing activity against Omicron underlinings on HEK293T / ACE2 target cells. However, all but one participant had weak but detectable neutralizing activity against Omicron VSV pseudotypes in VeroE6 / TMPRSS2 cells. The finding confirmed the role of target cell lines or viral entry pathways in the neutralization assays of observed GMT values.
Conclusions
Overall, the four Omicron subvariants examined in the current study had increased ACE2-binding affinity and decreased fusogenicity, but exceptional neutralizing antibody evasion potential compared to Wuhan-Hu- ancestors. 1 and Delta VOC. Taken together, the study data justify the rapid transmission of Omicron underlines worldwide and the reasons for the continued increase in the prevalence of Omicron BA.4 and BA.5 subvariants.
In addition, the current study highlighted that, despite the exceptional immune evasion potential of Omicron subvariants, additional booster doses with currently available vaccines could provide strong protection against serious disease due to infections. innovative. The study authors emphasized the importance of evaluating the time interval between vaccination doses to increase the amplitude and strength of neutralizing antibody responses against new SARS-CoV-2 VOCs and not yet emerged. They also stressed the importance of continuous surveillance to detect new variants of SARS-CoV-2 early. Most importantly, the authors recommended frequent evaluations of current COVID-19 vaccines and sustained efforts to develop and test new vaccines as a measure of preparedness against all sarbecovirus contingencies.