Study reveals how our immune system reacts to COVID-19 variants

Date:
July 7, 2021
Source:
University of Sydney
Summary:
New research into how our immune system responds to COVID-19
reveals that those infected by early variants in 2020 produced
sustained antibodies, but these antibodies are not as effective
against contemporary variants of the virus.



FULL STORY ========================================================================== Australian scientists researching how our immune system responds to
COVID-19 have revealed that those infected by early variants in 2020
produced sustained antibodies, however, these antibodies are not as
effective against contemporary variants of the virus.


==========================================================================
The research is one of the world's most comprehensive studies of the
immune response against COVID-19 infection. It suggests vaccination
is more effective than the body's natural immune response following
infection and shows the need to invest in new vaccine designs to keep
pace with emerging COVID variants.

Published today in PLOS Medicine, the study was made possible by a
partnership between the University of Sydney, Kids Research, Sydney
Children's Hospitals Network, the Kirby Institute at UNSW Sydney,
Australian Red Cross Lifeblood, St Vincent's Hospital and NSW Health
Pathology, as well as other local and international collaborators.

The team analysed the serum of 233 individuals diagnosed with COVID-19
over 7 months and uncovered that the level of immunity over time is
dependent on disease severity and the viral variant. They show that
antibodies developed during the first wave had reduced effectiveness
against six variants, ranging from those observed in the second wave
in Australia through to three variants of concern that have driven the
global pandemic in the UK, Brazil and South Africa.

How do we study the immune response? The serum of COVID-19 infected individuals was of interest as it is the part of our blood that contains crucial information about our immune system. Analysis of the serum made
it possible to create a detailed timeline of the level of 'neutralising antibodies' produced against COVID-19 infection, and so to see if there
was long-term immunity.



========================================================================== Neutralising antibodies are part of our immune system's frontline arsenal
that is triggered during infection and vaccination. Their job is to shield cells that are usually the target of a pathogen (such as the SARS-CoV-2
virus which causes the COVID-19 disease) from being infected. The level
of neutralising antibody response can be a defining feature of how
effectively our body fights off illness.

Interestingly, a rare group of 'super responders' was also identified
as an exception.

This group of 'super responders' had a stable and robust level of
antibodies across all COVID-19 variants. The researchers say this group
could prove useful for investigating the potential of convalescent plasma (using blood from people who have recovered to treat others) which has
so far proven ineffective against severe COVID-19 illness. In addition,
key donors could be looked at closely and their antibodies cloned for
future therapeutic use.

Why it is important? Co-senior author Associate Professor Fabienne Brilot
of the University of Sydney and Kids Research, Sydney Children's Hospitals Network, and her research team led the analysis branch of the study, using highly sensitive tools they developed to study the antibodies in detail.



==========================================================================
"We can learn a great deal from these people who were infected in the
first wave in Australia as they were infected with the same variant that
our current vaccines are based on," said Associate Professor Brilot.

"While the approved vaccines are showing good responses, our study
highlights the importance of continued vaccine development, especially
taking into account the differences in variants." Co-senior author
Associate Professor Stuart Turville of the Kirby Institute said the
study was conducted to investigate the level, breadth and longevity of
the immunity generated from COVID-19 infection and whether mutation of
the virus compromises immunity.

"What this work has shown us is that current observations about vaccines
show they offer a much broader protection against COVID-19 and its
variants than the body's natural immune response following infection,
which is usually only protective against the variant of the virus that
the person was infected with.

We, therefore, should not rely on the body's natural immune response to
control this pandemic, but rather the broadly protective vaccines that
are available." Key findings
* SARS-CoV-2 antibody responses are sustained for up to seven
months post-
infection.

* The immune response remained stable in some individuals, and
while it
decreased in others, no individual showed a negative response
during the seven-month period.

* Levels of virus-neutralising antibodies were associated with
COVID-19
severity.

* Antibodies generated after early infection displayed a significantly
reduced antibody binding and neutralisation potency to globally
emerging viral variants.

Methods The study analysed the serum from 233 individuals who were
diagnosed with COVID-19 from February to October 2020. There were two
cohorts to the study - - a hospital-based cohort of patients (the ADAPT
study at St Vincent's Hospital, Sydney) recruited during the first and
second wave of infection in Australia and a national cohort of plasma
donors (LIFEBLOOD).

10 COVID-19 strains and variants of concern/ interest were investigated, including:*
* First known classified SARS-CoV-2 strain (Wuhan -1 D614) * Alpha
(B.1.1.7, United Kingdom) * Beta (B.1.351, South Africa) * Gamma
(P1, Brazilian) * Zeta (P2, Brazilian)
*Note naming conventions updated to reflect World Health Organisation classifications The researchers used a comprehensive suite of assays
that measured:
* The longevity and type of antibody response against Spike from
various
variants over time in serum of COVID-19 diagnosed individuals.

* Neutralisation of infectious SARS-CoV-2 over time, by infecting cell
lines that had ACE2 on its surface (which SARS-CoV-2 binds and
targets on the cell to begin infection) with a particle designed
to mimic a version of the SARS-CoV-2 virus particle.

The study of many global viral variants was made possible by the key collaboration between NSW Health Pathology and The Kirby Institute. The
latter team engineered cells to rapid catch virus from swabs that were
acquired and rapidly sequenced by the team at Prince of Wales headed by Professor William Rawlinson.

Co-first author Fiona Tea who completed the research as part of her early postdoctoral fellowship at the University of Sydney and Kids Research at
the Children's Hospital at Westmead said: "What makes this study stand
out is the level and depth of analysis to neutralising antibody levels in people recovering from COVID infection over time, including comparison
of infection recovering from different viral variants." Declaration:
This work was supported by Snow Medical and various grants including
two NSW Health COVID-19 Research Grants and multiple grants from the
Australian Government's Medical Research Future Fund (MRFF), among others.

Refer to the paper for full details. Associate Professor Brilot has
received honoraria from Biogen Idec and Merck Serono as an invited
speaker. All other authors declare no competing interest. Ethics approval
for this study was granted by St Vincent's Hospital (2020/ETH00964)
and Lifeblood (30042020) Research Ethics Committees.

========================================================================== Story Source: Materials provided by University_of_Sydney. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Fiona Tea, Alberto Ospina Stella, Anupriya Aggarwal, David Ross
Darley,
Deepti Pilli, Daniele Vitale, Vera Merheb, Fiona X. Z. Lee, Philip
Cunningham, Gregory J. Walker, Christina Fichter, David A. Brown,
William D. Rawlinson, Sonia R. Isaacs, Vennila Mathivanan, Markus
Hoffmann, Stefan Po"hlman, Ohan Mazigi, Daniel Christ, Rebecca
J. Rockett, Vitali Sintchenko, Veronica C. Hoad, David O. Irving,
Gregory J. Dore, Iain B.

Gosbell, Anthony D. Kelleher, Gail V. Matthews, Fabienne Brilot,
Stuart G. Turville. SARS-CoV-2 neutralizing antibodies: Longevity,
breadth, and evasion by emerging viral variants. PLOS Medicine,
2021; 18 (7): e1003656 DOI: 10.1371/journal.pmed.1003656 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210707112416.htm

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