Prior exposure to common cold coronaviruses enhances immune response to SARS-CoV-2

Date:
September 2, 2021
Source:
Charite' - Universita"tsmedizin Berlin
Summary:
Researchers have shown that certain immune cells, which are found in
people previously exposed to common cold coronaviruses, enhance the
body's immune response to SARS-CoV-2, both during natural infection
and following vaccination. The researchers also report that this
'cross- reactive immunity' decreases with age. This phenomenon may
help to explain why older people are more susceptible to severe
disease and why their vaccine-induced immunity is often weaker
than that of young people.



FULL STORY ========================================================================== Researchers from Charite' -- Universita"tsmedizin Berlin, the Berlin
Institute of Health at Charite' (BIH) and the Max Planck Institute for Molecular Genetics (MPIMG) have shown that certain immune cells, which
are found in people previously exposed to common cold coronaviruses,
enhance the body's immune response to SARS-CoV-2, both during natural
infection and following vaccination. The researchers, whose work has been published in Science, also report that this 'cross-reactive immunity'
decreases with age. This phenomenon may help to explain why older people
are more susceptible to severe disease and why their vaccine-induced
immunity is often weaker than that of young people.


==========================================================================
Last year, researchers from Charite' and the MPIMG made a surprising
discovery.

They were the first to report that individuals with no prior exposure
to SARS- CoV-2 nonetheless had immunological memory cells capable of recognizing this novel virus. The researchers concluded that these
'T helper cells' must have been generated to deal with mostly harmless
common cold coronaviruses and that, thanks to the structural similarities between coronaviruses (in particular the characteristic spike protein
found on their outer surface), these T helper cells will also attack
the novel coronavirus. This 'cross reactivity' hypothesis has since been confirmed by a range of studies.

Still unclear, however -- and the object of intense debate --
is the question of whether these immune cells affect the course of
subsequent SARS-CoV- 2 infections. "Our assumption at the time was that cross-reactive T helper cells have a protective effect, and that prior
exposure to endemic (i.e. long- established and widely circulating) coronaviruses therefore reduces the severity of COVID-19 symptoms," says
the study's (and the previous study's) first author, Dr. Lucie Loyal,
a researcher based at both the Si-M ('Der Simulierte Mensch -- literally
'The Simulated Human', a joint research space of Charite' and Technische Universita"t Berlin) and the BIH Center for Regenerative Therapies
(BCRT). She adds: "However, the opposite could have been true. With
some viruses, a second infection involving a similar strain can lead
to a misdirected immune response and a negative impact on clinical
course." In the current study, the Berlin-based research team presents
evidence to support their previous assumptions regarding the existence
of a protective effect.

According to their data, cross-reactive immunity could be one of several reasons for the variability in disease severity seen with COVID-19 but
might also explain differences in vaccine efficacy seen in different
age groups.

For the current study, the researchers recruited individuals with no
prior exposure to SARS-CoV-2, testing them at regular intervals to
establish whether they had contracted the infection. Out of a total
of nearly 800 participants who were recruited from mid-2020 onwards, 17
persons tested positive. The researchers studied the affected individuals' immune systems in detail. Their analyses showed that the immune response against SARS-CoV-2 also included the mobilization of T helper cells
which had been generated in response to endemic common cold viruses. The researchers also showed that the quality of the immune response against SARS-CoV-2 was linked to the quantity of cross-reactive cells which had
been present in the body prior to infection. These cells were particularly effective at recognizing a certain area of the spike protein. In both the endemic viruses and the new coronavirus, this site was characterized by sequence similarities which were particularly well 'preserved'. "During infections with the more harmless coronaviruses, the immune system builds
up a kind of protective 'universal coronavirus' memory," explains the
study's corresponding author, Dr. Claudia Giesecke-Thiel, Head of the
Flow Cytometry Service Group at the MPIMG. "Once exposed to SARS-CoV-2,
these memory cells are reactivated and kick-start the response against
the new pathogen. This could help accelerate the initial immune response
to SARS-CoV-2 and limit viral propagation during the early stages of
the infection and is therefore likely to have a positive effect on the
course of the disease." Taking a more cautionary tone, the researcher
adds: "This does not mean that prior exposure to common cold viruses
will definitely protect an individual against SARS-CoV-2, nor does it
change the course of the pandemic as of now because these underlying
mechanisms have been operating all along. It in no way diminishes the importance of getting vaccinated. Our study provides one of several explanations for an observation made since the beginning of the
pandemic, namely that the symptoms of SARS-CoV-2 infection can vary
greatly between individuals." The researchers' findings furthermore
confirmed that the immunity-enhancing effects of cross-reactive T
cells also occur following vaccination with the BioNTech COVID-19
vaccine. Just like natural infection, the vaccine prompts the body
to produce the SARS-CoV-2 spike protein (including the well-preserved
section of it) and present it to the immune system. An analysis of the
immune responses of 31 healthy individuals before and after vaccination revealed that, while the activation of normal T helper cells took place gradually over the course of two weeks, the activation of cross-reactive
T helper cells was extremely rapid, taking place within one week of vaccination. Naturally, this also had a positive effect on the generation
of antibodies. Even after the first dose of the vaccine, the body was
able to produce antibodies against the preserved section of the spike
protein at a rate normally only seen after booster vaccinations. "Even following vaccination, the body is able to utilize at least some of its immunological memory -- provided it has had previous exposure to endemic coronaviruses," says co-corresponding author Prof. Dr.

Andreas Thiel, a Charite' researcher based at both the Si-M and the
BCRT. He adds: "This might explain the surprisingly rapid and extremely
strong protective effect we see after the initial dose of the COVID-19
vaccine, at least in younger individuals." In a second part of the
study, the researchers analyzed T helper cells in approximately 570
healthy individuals. They were able to show that cross- reactive immunity declines in older adults. In fact, both the number of cross- reactive
T cells and the strength of their binding interactions was shown to be
lower in older participants than in younger participants. According to
the authors, this decline in cross-reactive immunity is caused by normal,
age- related changes. "Infection with an endemic coronavirus represents
a benefit in younger people, helping them fight off SARS-CoV-2 or develop immunity following vaccination. Sadly, this benefit is less pronounced in
older adults," says Prof. Thiel. He adds: "It is likely that a third (or booster) dose would be able to compensate for this weaker immune response, ensuring that members of this high-risk group have adequate immunity."
Common cold coronaviruses The four endemic coronaviruses which have been circulating in humans for some time are generally referred to as human
endemic coronaviruses (HCoV). The four viruses, all of which usually
cause symptoms of the common cold, are known as HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63. Estimates suggest they are responsible for up
to 30 percent of all seasonal colds.

T helper cells T helper cells are responsible for regulating and
coordinating the body's immune response. Once a pathogen invades
the body, cells known as macrophages and dendritic cells engulf the
pathogen, break it up and present fragments of it ('antigens') on their
cell surface. T helper cells scour these fragments. If the T helper
cell carries a receptor which recognizes these activating fragments,
the T helper cell is activated. Activated T helper cells then prompt
other immune cells to mount a direct response against the pathogen and
produce precisely fitting antibodies. Most immune responses will also
generate memory T cells, which can persist in the body for many years
and are responsible for the body's ability to mount a faster and more
effective immune response upon re- exposure to the same pathogen. One characteristic feature of T helper cells is that their activation is
not dependent on pathogens which are a perfect match.

Rather, they can be activated by pathogens with 'sufficient similarity'.

On this study This research is based on the 'Charite' Corona Cross'
study, which was launched in 2020, and is being led by Charite' and
conducted in cooperation with Technische Universita"t Berlin and the
MPIMG. Funded by the Federal Ministry of Health (BMG), the 'Charite'
Corona Cross' study investigates the impact of cross-reactive T helper
cells on the course of COVID-19. Elements of this research formed part
of a collaborative project known as 'COVIM -- Determining and using
immunity to SARS-CoV-2'. The aim of the COVIM consortium is to study
who has protective immunity to SARS-CoV-2, how this is achieved and how
long it lasts. A further aim is to study how to transfer the protective immunity of a few individuals to a large number of people without such immunity. The project is being coordinated by Charite' and University
Hospital Cologne. COVIM is one of 13 large collaborative research
projects conducted under the auspices of the NUM academic research
network. Initiated and coordinated by Charite', the NUM is funded by
the Federal Ministry of Education and Research (BMBF). The NUM brings
together the combined strength of Germany's 36 university hospitals.

========================================================================== Story Source: Materials provided by
Charite'_-_Universita"tsmedizin_Berlin. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Lucie Loyal, Julian Braun, Larissa Henze, Beate Kruse, Manuela
Dingeldey,
Ulf Reimer, Florian Kern, Tatjana Schwarz, Maike Mangold, Clara
Unger, Friederike Do"rfler, Shirin Kadler, Jennifer Rosowski,
Ku"brah Gu"rcan, Zehra Uyar-Aydin, Marco Frentsch, Florian Kurth,
Karsten Schnatbaum, Maren Eckey, Stefan Hippenstiel, Andreas Hocke,
Marcel A. Mu"ller, Birgit Sawitzki, Stefan Miltenyi, Friedemann
Paul, Marcus A. Mall, Holger Wenschuh, Sebastian Voigt, Christian
Drosten, Roland Lauster, Nils Lachman, Leif-Erik Sander, Victor
M. Corman, Jobst Ro"hmel, Lil Meyer- Arndt, Andreas Thiel, Claudia
Giesecke-Thiel. Cross-reactive CD4+ T cells enhance SARS-CoV-2
immune responses upon infection and vaccination.

Science, 2021; eabh1823 DOI: 10.1126/science.abh1823 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210902174754.htm

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