New insights into antibody responses to omicron variants

New insights into antibody responses to omicron variants

Science (2022). DOI: 10.1126/science.adc9127″ width=”800″ height=”530″/>
Structural characterization of the pan-variant mAb S2X324. (A) Cryo-EM structure seen along two orthogonal orientations of the SARS-CoV-2 Omicron BA.1 S prefusion ectodomain trimer with three linked S2X324 Fab fragments. SARS-CoV-2 S protomers are colored light blue, pink and gold. The S2X324 heavy chain and light chain variable domains are colored purple and magenta, respectively. Glycans are rendered as blue spheres. (B) Ribbon diagram of SARS-CoV-2 RBD bound to S2X324. The N343 glycan is rendered as blue spheres. (C) Magnified view of contacts formed between S2X324 and SARS-CoV-2 BA.1 RBD. Selected epitope residues are labeled and electrostatic interactions are indicated by dotted lines. A few of the identified escape mutants are turquoise in color. (D) Overlay of S2X324 bond (purple and magenta) and ACE2 bond [dark gray, PDB 6M0J (94)] SARS-CoV-2 RBD structures (light blue) showing steric overlap. The N343 glycan is rendered as blue spheres. Credit: Science (2022). DOI: 10.1126/science.adc9127

Knowing how well vaccination against one strain of SARS-Co-V2 (with or without previous infection) neutralizes infection with a different strain is a key research question. The answers could guide strategies to keep the COVID pandemic under control, even as the coronavirus regains ground.

Recent scientific studies in this area have been conducted by the laboratories of David Veesler, associate professor of biochemistry at the University of Washington in Seattle and researcher at the Howard Hughes Medical Institute, and Davide Corti of Humabs BioMed SA of Vir Biotechnology in Switzerland.

Their latest findings appear in this week’s issue Science in the article “Printed antibody response against SARS-CoV-2 Omicron sublines”.

The main authors of the article are Young-Jun-Park, Dora Pinto, Alexandra C. Walls and Zhuoming Liu. Young-Jun-Park and Lexi Walls are from the Veesler lab, Dora Pinto is from the Corti lab, and Zhuoming Liu is at Washington University in St. Louis.

The international team examined several aspects of the effects of exposure to earlier forms of the SARS-CoV-2 spike antigen – or immune-provoking protein – on the immune system’s response to omicron variants.

The omicron variants of the SARS-CoV-2 virus emerged in late 2021 and show marked genetic differences from the ancestral SARS-CoV-2. The many distinct mutations in their infection machinery allowed them to evade antibodies from the original series of vaccines, history of infection, or both of these immune system training events.

Antibodies are immune proteins that recognize tiny foreign entities, like viruses, and then neutralize them by latching onto the invader.

Previous studies by the same team noted that the BA.1 omicron variant emerged as a “major antigenic shift due to the unprecedented scale of immune evasion associated with this worrying variant.” They explained that mutations in two of the main antibody targets of the virus explain why the neutralizing capacity of antibodies against these variants is markedly reduced, especially in people who have not received booster doses.

“As a result, an increasing number of reinfections are occurring,” the scientists wrote in their paper, “even though these cases tend to be milder than in infections of immunologically naïve individuals.”

The evasiveness conferred by the mutations, they noted, also helps explain why most monoclonal antibody therapies given to patients in the clinic are less effective against these variants. However, the researchers identified a pan-variant, ultra-potent neutralizing antibody, named S2X324, that stood out. Its neutralizing power was largely unaffected by any of the omicron variants tested.

The authors show that this monoclonal antibody prevents binding to the receptor on host cells that the pandemic coronavirus usually commandeers. The scientists also suggested that combining this antibody with others in a cocktail could reduce the chances of the virus becoming resistant to antibody treatment.

Through their experiments, the scientists learned that vaccine boosters and hybrid immunity (acquired through history of infection and vaccination) both induce neutralizing antibodies in the blood against omicron BA.1, BA.2, BA.2.12.1 and BA.4 /5.

People who had a breakthrough infection after vaccination also produced neutralizing antibodies against these variants in the mucus that lines the inside of their nose. However, people who only received the vaccine did not generate antibodies in their nasal mucosa. This finding supports efforts to develop and evaluate next-generation COVID vaccines that could be administered intranasally, as the nose is typically the site where the virus first enters the body.

The scientist also determined that antibody responses to the pandemic coronavirus follow a pattern similar to how the immune system responds to flu virus variations. This phenomenon is called immune fingerprinting. This means that the immune response shows a preference for recalling existing memory B cells specific against parts of the virus present in a strain to which an individual has been previously exposed, rather than priming new memory B cells targeting the differences present. in distinctly different strains upon infection.

While this can be useful in stimulating a cross-attack, the scientists explain, previous exposure to earlier versions of a virus can sometimes hamper a more specific response against a virus that has mutated significantly.

COVID-19 boosters provide better immunity against SARS-CoV-2 variants in older Singaporeans

More information:
Young-Jun Park et al, Printed Antibody Responses Against SARS-CoV-2 Omicron Sublines, Science (2022). DOI: 10.1126/science.adc9127

Provided by University of Washington School of Medicine

Quote: New Insights on Antibody Responses to Omicron Variants (2022, October 24) Retrieved October 24, 2022 from

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