New insights into antibody responses to Omicron variants

Understanding how vaccination against one strain of SARS-CoV-2 (whether previously infected) can effectively counteract infection with different strains is a key research question
.
These answers can guide strategies to continue to contain the COVID pandemic, even as it returns
.

Recent scientific research in this area was led by David Veesler, associate professor of biochemistry at the University of Washington in Seattle, and Howard Hughes Medical Institute Fellow, and Davide Corti of Humabs BioMed SA, a Swiss vir biotechnology company
.
Their latest findings are published this week in the journal
Science.

The paper's lead authors are Young-Jun-Park, Dora Pinto, Alexandra C.
Walls, and Zhuoming Liu
.
Young-Jun-Park and Lexi Walls are from Veesler's lab, Dora Pinto is from Corti's lab, and Zhuoming Liu works at Washington University
in St.
Louis.
The international team investigated several aspects
of the effects of exposure to the early form of SARS-CoV-2 spike antigen (or immunoprovocative protein) on the immune system's response to the Omicron variant.

The Omicron variant of the SARS-CoV-2 virus appeared at the end of 2021 and has significant genetic differences
from the ancestral SARS-CoV-2 virus.
They have many different mutations in their infection mechanisms, which allow them to escape antibodies caused by the initial series of vaccines, escape the history of infection, or escape both immune system training events
.

Antibodies are immune proteins that recognize tiny, foreign entities, such as viruses, and then neutralize them
by adsorbing invaders.
Past studies from the same team noted that the Omicron variant of BA.
1 showed "significant antigenic metastasis due to the unprecedented scale of immune evasion associated with the variant of concern.
"
They explain that mutations in the two main antibody targets in the virus explain why antibodies are significantly less able to neutralize these variants, especially in
people who did not receive a booster dose.
"The result is an increasing number of reinfections, although these cases tend to be milder
than unimmunized people," the scientists wrote in their paper.
They note that the evasive power of mutations also helps explain why most monoclonal antibody therapies given to patients clinically are less
effective against these variants.
However, the researchers did find a panvariant and super-neutralizing antibody
called S2X324.
Its neutralizing potency is largely unaffected by
the Omicron variant.

The authors show that this monoclonal antibody blocks binding to receptors on host cells, which pandemic coronaviruses normally occupy
.
The scientists also suggested that mixing this antibody with other antibodies to make a cocktail might reduce the chances of
the virus developing antibody resistance.

Through their experiments, the scientists learned that both vaccine boosters and mixed immunity (acquired through a history of infection and vaccination) induce neutralizing antibodies in the blood against Omicron BA.
1, BA.
2, BA.
2.
12.
1 and BA.
4/5
.

People who develop a breakthrough infection after vaccination also develop neutralizing antibodies in the mucus inside their nose to fight these variants
.
However, people who were only vaccinated did not develop antibodies
in the nasal mucosa.
This finding provides support for the development and evaluation of the next generation of COVID vaccines, which can be injected intranasally, as the nose is often where the virus first enters the
body.

The scientist also determined that the antibody's response to the pandemic coronavirus follows a pattern, similar to the immune system's response
to the mutation of the flu virus.
This phenomenon is called immunoblotting
.
This means that the immune response is more inclined to recall existing memory B cells, targeting the portion of the virus present in the virus strain that an individual has been previously exposed to, rather than activating new memory B cells at the time of infection, targeting differences
in significantly different virus strains.
The scientists explain that while this helps stimulate cross-variant attacks, previous exposure to earlier versions of the virus can sometimes hinder more specific responses
against viruses that are significantly mutated.

Imprinted antibody responses against SARS-CoV-2 Omicron subvariants