New information on antibody responses to omcron variants

Knowing how vaccination against one SARS-CoV-2 strain (with or without previous infection) counteracts infection with a different strain is an essential research matter. The responses could guide strategies to keep the COVID pandemic under control, even as the coronavirus picks up ground.

Recent scientific studies in this field 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 journal Science in the article “Imprinted Antibody Response Against SARS-CoV-2 Omiron Underlines.”

The lead authors of this 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 looked at several aspects of the effects of exposure to earlier forms of the SARS-CoV-2 spinal antigen – or immune system stimulating protein – on the immune system’s response to Omicron variants.

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

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

Previous studies by the same team found that the Omicron BA.1 variant emerged as a “major antigenic shift due to the unprecedented scale of immune evasion associated with this disturbing variant.” They explained that mutations in two of the virus’s main antibody targets explain why the neutralizing ability of antibodies against these variants is greatly 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, “although these cases tend to be milder than infections of immunologically naive individuals.”

The evasiveness conferred by the mutations, they note, also helps explain why most monoclonal antibody treatments given to patients in the clinic are less effective against these variants. However, the researchers identified an ultra-potent pan-variant neutralizing antibody, called 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 host cell receptor that the pandemic coronavirus usually commits. Scientists have 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 the 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 lining the inside of the nose. In contrast, people who only received the vaccine did not produce antibodies in the nasal mucosa. These findings support efforts to develop and evaluate next-generation COVID vaccines that could be administered intranasally, with the nose typically being the site where the virus first enters the body.

The scientist also determined that antibody responses to the pandemic coronavirus follow a similar pattern to how the immune system responds to changes in the flu virus. This phenomenon is called immune fingerprinting. This phenomenon is called immune fingerprinting, i.e. the immune response prefers to recall existing B lymphocytes from memory, specific to the parts of the virus present in a strain to which an individual has been previously exposed, rather than triggering new memory B lymphocytes targeting the differences. present in very different strains at the time of infection. While this can be useful in spurring a cross-attack, scientists explain, having been exposed to earlier versions of a virus can sometimes hinder a more specific response against a virus that has mutated significantly.