The Complex Immune

Reaction of Coronavirus
Infection and Vaccination
Prof. Dr. Asem Shehabi
School of Medicine
University of Jordan
KEMENTERIAN AGAMA REPUBLIK INDONESIA
UNIVERSITAS ISLAM NEGERI MAULANA MALIK
IBRAHIM MALANG FAKULTAS KEDOKTERAN
DAN ILMU ,Saturday 24 April 2021
 Introduction

Currently, 6 types of vaccines are widely

used in vaccination worldwide
Numerous studies have been performed
to understand the immune response
involved in COVID-19 infection and its
prevention by vaccination.
 SARS-CoV-2 antigenic
structures
Coronavirus-2 (SARS-CoV-2) consists of a positive
sense single stranded RNA genome coated by a
nucleocapsid protein (N-protein) enclosed in a lipid
envelope derived from the host membrane.
Its Genes express structural & nonstructural
proteins.
Structural proteins are following: The glycoprotein
spike (S-protein), the envelope protein
(E-protein), and the membrane/matrix protein (M-
protein) are mostly involved in immune response
(Figure 1).
Main Structures of SARS-CoV-2
2/
The other structural N protein is a multifunctional
viral protein involved in the processes such as viral
assembly, budding, RNA replication, and host cellular
response, and it can act as a potent Interferon
antagonist during viral infection.
The SARS-CoV-2 receptor binding domain (RBD),
being part of the S-protein domain, binds to the
angiotensin converting enzyme-2 (ACE 2) receptor in
host cells mainly via the
S1 subunit, allowing virus to entry into the host cell.
 3/
The S protein is the main antigen component
in all structural proteins of this virus.
Unlike other functional proteins of the virus, it is
responsible for inducing the host immune
response, and antibodies targeting the
S protein can induce protective immunity
against viral infection… Many studies found that
neutralizing antibodies were directed against
the S-protein responsible for cell attachment.
 Corona Vaccine Development
Normally, a vaccine takes 10 to 15 years to be
developed safely and efficiently, but in this
coronavirus pandemic, vaccine development
was expected to occur at higher rates, with
rapid human testing.
The first step of designing a vaccine requires
the selection of antigens capable of inducing
an immune response, followed by the
selection of a platform, a route of
administration along with a safe regimen of
doses.
Immunity against COVID-19
COVID-19 is acquired via the respiratory route,
after interaction of the S-protein-RBD with
ACE2 receptor.
Like all other respiratory viruses, the immune
response will initiate mobilization of its different
arms starting with the innate immune system.
COVID-19 plays a major role in the
suppression of dendritic cell activity along
with inhibition the production of interferon
type I and type III responses, and the elevation
of systemic cytokines, mainly interleukin-6.
 2/Immunity

Thus, adaptive immunity, as a second line of

defense, will gear up with its two components:
Th1 cellular immunity and Th2 humoral
immunity.
Antibody-mediated immunity is fundamental
for virus neutralization, mainly via antibodies
directed against the S-protein, which makes
the antigenic epitope the basis for most
serological rapid diagnostic tests targeting IgM
and IgG detection.
 3/Immunity

This fact raises the possibility of designing

vaccines against proteins that mutate
less frequently than spike, and
incorporating targets from multiple proteins
into one vaccine.
Nature 590, 374-375 (2021)
Coronavirus Serological Test
Serologic tests for COVID-19 infection are based
on detection antibodies that measure a
person’s humoral immune response to the
virus. The tests detect IgG, IgM, or both.
Antibodies typically become detectable
approximately 2 or more weeks after the onset
of symptoms.
How long these antibodies stay detectable
and their durability is not yet known.
A positive result suggests that the person has
potentially been exposed to COVID-19 infection.
 2/Serological tests
When immunoglobulins M (IgM) antibodies are
present, they can indicate an active or recent
infection, whereas (IgG) antibodies show up
later in the infection process and can often
indicate a past infection
Both can’t exclude recently infected patients who
can still be contagious, especially when IgM
antibodies are also concurrently detected.
In all viral infections, IgG antibodies usually
persist longer than IgM antibodies and provide
immunity from re-infection, but this process is
not clearly known if that is true for COVID-19.
 3/Serological tests
The Geometric mean titers of
antibodies can range between 1- 2048
Antibody testing is not currently
recommended to assess for immunity
to COVID-19 following COVID-19
vaccination
 Duration of immunity
The exact magnitude and duration of the
protective immunity naturally or after
vaccination is still under investigation.
Many studies have shown that the antibody
response is positively related to disease severity.
That is, the more the severe the COVID-19
infection, the higher antibody titer. So far,
evidence reported from USA study suggests that
the spike-RBD-S2 and neutralizing antibodies
remain detectable for up to 7-8 months post
infection, both in natural infection or using a
vaccine.
 2/Duration Immunity
According to a recent study in India, natural
immunity in form of antibodies against COVID-19
lasts for 6 to 7 months.
The study also stated that between 20-30% of those
infected with the virus loss these antibodies after a
6-month period.
Research on the immunity period of COVID-19
vaccines is still ongoing, but most vaccines
currently in use are expected to protect from severe
coronavirus infection or death for at least a couple
of years since they produced specific antibodies.
 3/Duration Immunity

Specific antibodies are not the only immunity fight

COVID-19 virus.
Another important role is the cellular immunity via
CD8 positive T-cells that will also help in viral
clearance.
Antibody production is a multi-step process that
involves interactions between several cellular types.
Coordination and interaction between CD4 and CD8
positive T-cells, and the memory cells are playing
a major role in the immune defenses against
invading coronavirus.
 Complication of Immunity
Deaths associated with COVID-19 are
principally due to hyperinflammation and
uncontrolled immune response.
The COVID-19 infection triggers a
cytokine storm characterized by
potentially life-threatening manifestations
such as hyper-inflammation, septic shock
complications, coagulation dysfunction,
and impairment of several vital organs.
 Important issues related to immune
response
When 2 persons receive the same
coronavirus vaccine, their side effects
may likely differ. That's because each
person's immune system is unique.
How a person responds to vaccines
depends on many factors like age and sex,
as well as more individual health
characteristics like his genes or history of
exposure to previous infection.
 2/Important issues
In general, women and younger adults tend to
have the most severe side effects after their
vaccination, no matter the dose or source.
For all three US-authorized coronavirus
vaccines – from Pfizer, Moderna, and Johnson &
Johnson.
A recent USA study has shown that younger
adults more commonly reported fatigue,
headache, and pain at the injection site than
older adults did. Side effects are also more
numerous and severe after dose two of Pfizer's
or Moderna's shot.
 3/Important issues
Adults over 65 generally have weaker immune
systems
Our immune systems tend to deteriorate as we age,
so older people's bodies don't work as hard to
defend them against foreign invaders – including
the protein introduced to the body via a vaccine.
As a result, side effects are often milder and less
numerous among the elderly than among younger
adults.
Elderly persons are referring to individuals over
65.
 4/Important Issues
Estrogen plays a role in a woman's
immune response
Women tend to have stronger reactions
to many vaccines, including those for
polio, influenza, measles, and mumps – so
it's no surprise that they have more side
effects after their coronavirus shots, too.
Testosterone tends to be an immune-
suppressive hormone, and estrogen
tends to be an immune stimulant.
 Conclusion

The complex immunologic interaction

in response to COVID-19 infection is
still not well explained.
many hidden facts should be
investigated for future successful
therapeutic approaches and
vaccination