An Overview of Covid-19 Antibodies Using Proteomic Approach For Detection and Neutralization of Sars-Cov-2

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An Overview of COVID-19 Antibodies Using Proteomic Approach for Detection and

Neutralization of SARS-CoV-2

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the


causative agent of coronavirus disease 2019 (COVID-19), was declared a pandemic infection in
March 2020. The SARS-CoV-2 pandemic has endangered global health, the world economy,
and societal values. Despite intensive measures taken around the world, morbidity and mortality
remain high as many countries face new waves of infection and the spread of new variants.
Understanding the humoral antibody response to SARS-CoV-2 proteins may help identify
biomarkers that can be used to detect and neutralize COVID-19 infection. Thus this study
focused on analyzing the proteomics of COVID-19 antibodies and how it contributes to the
detection and neutralization of SARS-CoV-2.

The SARS-CoV-2 Proteome

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)


belongs to the family of betacoronaviruses and contains a single-stranded RNA of
approximately 30 kb in length (Wu et al., 2020a). Generally, a mature SARS-CoV-2
virus has a polyprotein (Orf1ab), four structural proteins (envelope – E; membrane – M;
nucleocapsid – N; spike – S), and five accessary proteins (Orf3a, Orf6, Orf7a, Orf8, Orf10).The
process of SARS-CoV-2 infection begins with the binding of the viral glycoprotein spike S
protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2). After fusion occurs,
the type II transmembrane serine protease (TMPRSS2) present on the cell surface clears
ACE2 and activates the receptor-attached spike-like S protein (Hoffmann et al., 2020),
leading to conformational changes necessary for virus entry. Following entry into the host
cell, the virus releases its genome, which is composed of RNA that undergoes replication and
transcription to produce multiple viruses that exit the cell to infect other cells [2–4]. The binding
of S protein to ACE2 is a crucial process of the infection, hence it is targeted by various
therapies to prevent COVID-19.

COVID-19 Antibody for Detection and Neutralization of SARS-CoV-2 using Proteomic


Analysis

SARS-CoV-2 infection begins when the RBD of the S protein of the virus binds to the ACE-2
receptor site in human cells, the initial step in viral entry into human cells. Preventing SARS-
CoV-2 from binding with ACE-2 receptors in the respiratory tract of humans can prevent
infection and illness. (34) This interaction between the S protein of SARS-CoV-2 and the ACE-2
receptor sites has been the major focus of various therapies to prevent COVID-19. One
therapeutic approach is the use of antibodies that bind specifically to viral S protein and RBD,
leading to the neutralization so that they can no longer interact with ACE2.

COVID-19 Antibody for Detection of SARS-CoV-2

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates a


cell-mediated and humoral immune response that produces antibodies against specific viral
antigens such as the nucleocapsid (N) protein and spike (S) protein. These include anti-S
protein antibodies that target the spike’s S1 protein subunit and receptor binding domain (RBD).
Antibodies—including IgM, IgG, and IgA—against S and its subunits can be detected in serum
within 1-3 weeks after infection (7, 8). IgM and IgG antibodies can arise nearly simultaneously
(7); however, IgM (and IgA) antibodies decay more rapidly than IgG (7, 9). An antibody tests for
SARS-CoV-2 assess IgM and/or IgG to one of two viral proteins: S or N. A positive test for S
IgM and/or IgG could indicate prior infection. To evaluate for evidence of prior infection in a
person with a history of COVID-19 vaccination, a test that specifically evaluates anti-N IgM/IgG
should be used. Testing for antibodies that indicate prior infection could be a useful public
health tool as vaccination programs are implemented, provided the antibody tests are
adequately validated to detect antibodies to specific proteins (or antigens).

COVID-19 Antibody for Neutralization of SARS-CoV-2

Nearly all immunocompetent persons develop an adaptive humoral immune response following
SARS-CoV-2 producing antibodies which offers some level of protection from reinfection
(Centers for Disease Control and Prevention). SARS-CoV-2 reinfection has been documented
(20, 21); however, studies indicate that persons with SARS-CoV-2 antibodies are less likely to
experience subsequent infection or clinical disease than persons without antibodies. With this,
in depth understanding of SARS-CoV-2 specific antibody responses is not only crucial for
development oof diagnostixs but aksi for epidemiological studies and intervention strategies
sych as vaccine development and monitoring.

SARS-CoV-2 reinfection has been documented (20, 21); however, studies indicate that persons
with SARS-CoV-2 antibodies are less likely to experience subsequent infection or clinical
disease than persons without antibodies. Investigations of outbreaks among people on a fishing
vessel and at a summer camp in the United States found that persons with pre-existing SARS-
CoV-2 antibodies were correlated with protection from subsequent infection (22, 23). In
sequential outbreaks among staff and residents of two British nursing homes, persons who
tested antibody-positive following the first outbreak were approximately 96% less likely to
become infected during the second outbreak four months later (24). A large study in the United
States of commercial laboratory results linked to medical claims data and electronic medical
records found a 90% reduction in infection among persons with antibodies compared with
persons without antibodies (25). Another study found that transfer of purified IgG from rhesus
macaques infected with SARS-CoV-2 was effective in protecting naïve rhesus macaques from
infection, and the threshold titers for protection, based upon binding and neutralizing antibodies,
were determined. Analyses of data from two vaccine trials found that higher titers of neutralizing
and anti-S binding antibodies correlated with more effective protection from infection.(28, 29)

Taken together, these findings in humans and non-human primates suggest that SARS-CoV-2
infection and development of antibodies can result in some level of protection against SARS-
CoV-2 reinfection. The extent and duration of protection have yet to be determined. While life-
long immunity has not been observed with endemic seasonal coronaviruses (30), studies of
persons infected with the SARS-CoV-1 and Middle East Respiratory Syndrome (MERS-CoV)
coronaviruses demonstrated measurable antibody for 18–24 months following infection (31, 32),
and neutralizing antibody was present for 34 months in a small study of MERS-CoV-infected
patients (33). It is not known to what extent persons re-infected with SARS-CoV-2 might
transmit SARS-CoV-2 to others or whether the clinical spectrum differs from that of primary
infection.

Considerations for public health and clinical practice

Accumulating evidence suggests that the presence of antibodies following infection offers some
level of protection from reinfection. Evidence includes the following: (1) reduced incidence of
infection among persons with SARS-CoV-2 antibodies followed for 3 months or longer; (2)
findings from outbreak investigations that pre-existing detectable antibody correlates with
reduced incidence of infection (22, 23, 26, 41); (3) challenge experiments in primates passively
immunized with convalescent plasma demonstrating prevention of infection (42); (4) viral
neutralization demonstrated with serum from persons following infection (5, 6); (5) data
demonstrating that vaccination, which also results in antibody production, can reduce the
incidence of illness (36, 37); and (6) decreased disease severity, and even prevention, of
infection associated with administration of monoclonal antibodies (43, 44).

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