A crucial research topic is how successfully infection with one SARS-CoV-2 strain can be prevented by immunization against another (with or without prior infection). The solutions could include measures to keep the COVID pandemic under control even as the coronavirus gains momentum.
David Veesler, an associate professor of biochemistry at the University of Washington in Seattle and a Howard Hughes Medical Institute investigator, and Davide Corti, of Humabs BioMed SA of Vir Biotechnology in Switzerland, have spearheaded recent scientific studies in this field.
This week’s issue of Science has an article called “Imprinted antibody response against SARS-CoV-2 Omiron sublineages” about their most recent research.
Young-Jun Park, Dora Pinto, Alexandra C. Walls, and Zhuoming Liu are the paper’s lead authors. Dora Pinto works in the Corti lab; Young-Jun Park and Lexi Walls are from the Veesler lab; Zhuoming Liu attends Washington University in St. Louis.
The impact of exposure to previous forms of the SARS-CoV-2 spike antigen, or immune-provoking protein, on the immune system’s response to the Omicron variations was examined from a number of angles by the worldwide team.
The SARS-CoV-2 virus’s Omicron versions first surfaced at the end of 2021 and differ significantly genetically from their ancestor. They have been able to avoid antibodies produced by the initial set of vaccines, from a history of infection, or from both of those two immune-system training events thanks to the numerous different mutations in their infection machinery.
Antibodies are immune proteins that can find tiny invaders like viruses and stop them from doing damage by binding to them.
They explained that mutations in two of the main antibody targets in the virus explain why there is markedly reduced antibody neutralizing ability against these variants, especially in people who have not received booster doses. In studies done by the same team before, the BA.1 Omicron variant was called a “major antigenic shift” because of the “unprecedented level of immune evasion” that it caused.
According to the researchers’ article, “as a result, more reinfections are happening, even though these cases tend to be milder than infections in immunologically naive individuals.”
They also pointed out that the majority of monoclonal antibody treatments administered to patients in clinics are less effective against these variants because of the evasive ability conferred by the mutations. However, a pan-variant and extremely strong neutralizing antibody known as S2X324 was found by the researchers to stand out. Neutralizing substances didn’t change much or at all with any of the Omicron variations that were tested.
The authors demonstrate that this monoclonal antibody blocks the pandemic coronavirus’s regular ability to hijack the receptor on host cells. Researchers also thought that mixing this antibody with others in a “cocktail” might make it less likely that the virus will become immune to antibody treatment.
Through their trials, the researchers discovered that Omicron variations BA.1, BA.2, BA.2.12.1, and BA.4/5 neutralizing antibodies are induced in the circulation by both vaccine boosters and hybrid immunity (acquired through a history of infection and vaccination).
Neutralizing antibodies against these variations were also created in the mucus lining the inside of the noses of those who experienced a breakthrough illness following vaccination. The nasal mucosa of those who simply got the vaccine, however, did not produce any antibodies. Since the virus usually gets into the body first through the nose, this finding backs up efforts to make and test next-generation COVID vaccines that could be given through the nose.
The researchers also discovered that the pattern of antibody responses to the pandemic coronavirus is comparable to that of immune system responses to different influenza virus strains. This process is known as immunological imprinting. It means that the immune response prefers to recall previously activated memory B cells that are specific against viral components found in a strain to which a person has been exposed, rather than prime new memory B cells to target differences found in noticeably different strains when an infection occurs. The researchers say that while this can help start a cross-variant attack, being exposed to earlier versions of a virus can sometimes stop a more focused response against a virus that has changed a lot.
