Complement System Response of Vaccinated Individuals With The Pfizer - Biontech and BBIBP-CorV (Sinopharm) Vaccines

CENTRAL ASIAN JOURNAL OF MEDICAL AND NATURAL SCIENCES
Volume: 04 Issue: 04 | Jul-Aug 2023 ISSN: 2660-4159

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Complement System Response of Vaccinated Individuals with

the Pfizer- Biontech and BBIBP-CorV (Sinopharm) Vaccines
1. Muna Neamah Salih Abstract:
2. Syoof Khoman Al-Ramahi Background: Coronavirus disease 2019 (COVID-19)
caused by SARS-CoV-2 is an contagious illness that
emerged in December 2019, remains a serious threat it
Received 2nd Jun 2023, has caused millions of deaths around the world,
Accepted 3rd Jul 2023, resulting in a global pandemic. COVID-19 vaccines
Online 5th Aug 2023 protect against this severe illness through different
approaches. Sinopharm and Pfizer-BioNTech COVID-
1, 2
19 vaccines were the greatest used vaccines in Iraq.
Department of Biology, College of Both vaccines have a specific mechanism to activate the
sciences / University of Al-Qadisiyah , Al- immune system in human body.
Qadisiyah, Iraq
[email protected] This research aims to assessment the complement
system C3 and C4 responses in vaccinated individuals
with each the Pfizer-BioNTech COVID-19 vaccine or
Key words: SARS-CoV-2, COVID-19 the Sinopharm vaccine.
vaccines, Complement system C3,
Methods
Complement C4.
The study included 180 Iraqi adults vaccinated with two
doses, 1 week apart, using either the Sinopharm or
Pfizer-BioNTech vaccine sixty person received the
Pfizer vaccine, sixty person received the Sinopharm
vaccine, and the other sixty subjects were un-vaccinated.
After one week, the second dose was administered, and
the blood samples were collected.
Results
study findings shown that Complement system 3 (C3)
and (C4) levels were significantly increased (P-value=<
P<0. 05) in total vaccinated groups when compared with
healthy control. also . the table was indicated C3
concentration was significantly high increased in first
dose compared to second dose on vaccinated group ,
while the C4 concentration was non-significantly
between two dose groups.
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CAJMNS Volume: 04 Issue: 04 | Jul-Aug 2023
The study concluded that the Pfizer-BioNTech and Sinopharm vaccine boosted the immune system
by high activation complement may also have a protective role and could function to enhance virus
neutralization by antibodies, promote virus phagocytosis by immune cells, and lysis of coronavirus.
1. Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is caused COVID-19 was first
recognized on Wuhan, China in December 2019 it is an infectious dangerous illness and spreads
speedily, World Health Organization (WHO) has been classified as a global health problem [1].
Coronavirus virus causing severe pneumonia , multi-organ dysfunction, or may death in extreme cases
of infection[2]. COVID-19 was spread by respiratory droplets when individuals sneeze ,cough or
exhale as well as may be spread by fomites [3]. There are many cases of asymptomatic carriers that
made it difficult to control the epidemic in many countries around the world , Urgent need for a way to
effectively stop the spread of the COVID-19 virus . Recently, many pharmaceutical companies have
produced numerous vaccines [4,5].
The Pfizer/BioNTech is a lipid nanoparticle-based BNT162b2 COVID-19 , It’s the first United States
Food and Drug Administration (FDA)-approved mRNA vaccine on December 2, 2020 is given in 2
doses three - weeks apart [6]. The demonstrated 95% efficacy of vaccine against symptomatic
COVID-19 disease [7]. Pfizer–BioNTech Vaccine doesn’t cause any serious side effects but often
causes short-lived symptoms for example fatigue, mild fever, muscle aches and pain at the injection
site [8].
The Sinopharm is attenuated or an inactivated COVID-19 vaccine, which is presently accepted by 65
countries [10] , which are developed by destroying the virus’ genetic material by chemicals, heating,
or radiation while preserving all viral proteins intact Thus, the whole virus vaccines are not infective
but can still activation the immune system response [11].
The systemic and local signs of the covid-19 vaccine are different attributable to the immune response
to the vaccination depends on various factors such as characteristics of the host age, sex, type of
vaccine, composition, method of administration and many other factors[9].
1.1. Role of Complement in COVID-19
The complement system is a structured system consisting of more than 30 whey proteins; Many of
them contain protease activity that enables one complement protein to activate another protein in a
cascade [21],Which consider the “first line of defense” against entering viruses and as a bridge
between innate and adaptive immune responses[23],
The adaptive immune response activated by classical pathway when happened interactions between
complement protein C1q and antibodies bound to antigens immunoglobulin IgG or IgM, as well as ,
The classical pathway can also occur as an innate response activated by natural IgM or preformed
auto-antibodies [14,15]. The remaining 2 pathways are innate immune responses that rapidly activate
against pathogens in an antibody-in-dependent way cause include the mannose-binding lectin (MBL)
pathway whereby directly binds to sugar particles attach to surface of pathogen, also , the alternative
pathway that occurs by spontaneous activation of C3 on target cells [16]. The complement system
supports immune body’ ability to fighting COVID-19 infection and preserve homeostasis[17]. All
three pathways leads to C3 protein activation and sub-sequent C5 activation cause cleavage of protein
into the C3a and C5a subunits, which play a major role in pro-inflammatory responses and recruitment
of immune cells( figure .1)[18].
Figure -1- Complement activation with COVID-19 patients.

The C3b protein cleavage product can adhere to virus, tagging them for uptake and degradation
(phagocytosis) by C3b receptors on immune cells [19].Furthermore Pathogen clearance can mediated
by the C5b part, which forms part of the (MAC) membrane attack complex that attachments with
membrane of target cell causing pore formation and lysis [19]. However, sub-lytic amounts of
membrane attack complex on the surface of nucleated cells can instead play a role in pro-liferation and
activation, as observed for Schwann cells and oligo-dendro-cytes [20]. Another important role of
complement is improvement of antibody neutralization ( n Ab )activity causing from C1q binding to
Ab even in the non-existence of other complement proteins [21].
This study aims to determine the effectiveness of Complement system 3 (C3) and (C4) after first and
second Pfizer-BioNTech and Sinopharm COVID-19 vaccines.
2. Materials and Methods
2.1. Study Design
In this research, a study was performed between December 2021 through September 2022. 180 male
and female Iraqi nationals from a Al-Diwaniyah city in Iraq .were conducted in this study. Their age
ranged from 20 to 60 years old divided to 60 individuals received the Pfizer vaccine , 60 received the
Sinopharm vaccine and 60 unvaccinated individuals formed the control group . Information about the
Iraqi people was collected using a standardized questionnaire platform. The form was divided into
three main sections, which were listed in the following order: demographic information, such as age,
gender, and place of residence; clinical information, such as prior COVID-19 infection ; chronic
disorders, drug utilization history, and vaccine details, such as the type of vaccine, number of dose
(first or second) severity and duration of any side effects.
The study was approved by the Senior Ethics Committee Public Health Department in the province
Written consent was taken from each vaccine recipient after explaining the purpose of the study.
2.2. Sampling Collection
The specimens were taken one week after the first and second vaccination injection. 5mL of whole
blood was drawn from each individual and placed in gel tubes and centrifuged for 15 min at 4000 rpm.
The serum was then split into three parts, placed in Eppendorf tubes, and stored at 20°C until use.
2.3. Inclusion and Exclusion Criteria
The adults Iraqi from Al Diwaniyah Governorate, who received two doses of the COVID-19 vaccine
(Pfizer-BioNTech and Sinopharm) and who agreed to participate were included in this study with
involved the Individual have pre-existing COVID-19 infection, who received only the first or second
dose of the above-mentioned COVID-19 vaccines, and those who did not receive the second dose
during the proposed period .
2.4. Immunological Biomarkers Measurement
The direct ELISA technology was Used to Measurement human Complement system 3 (C3) and (C4) .
It is suitable for in vitro semi-quantitative detection of human serum, A 5 μL was added to the ELISA
plate then added 495 μL of the dilute solution( DS), followed by 2 stages of washing then drying. The
reaction was stopped by adding a stop solution. Lastly, use the ELISA reader at a wavelength of 450
nm to read plate ,The results were then calibrated with the standard curve and final values were
extracted.
2.5. Statistical Analysis
The data were subjected to ANOVA analysis at a probability level of 0.05, and then using Graph
Prism 7 program for knowing the significant differences of the studied criteria included.
Figure.3.3. Standard curve for human C3 by ELISA
Figure.3.2. Standard curve for human C4 by ELISA

3. Results
The present study showed that serum Complement system 3 C3 and C4 levels were significantly
increased (P-value=< P<0. 05) in total vaccinated groups when compared with healthy control as
shown in table (3.1) . Also, the table was indicated C3 concentration was significantly high
increased in first dose compared to second dose vaccinated group , while the C4 concentration was
non-significantly between two dose groups as shown in table (3.2).
Table (3.1 ) Descriptive analysis of serum Complement C3 and C4 .
Parameters Control patients
Calculated
Mean ±Standard error
P value
range
3.19±0.29 13.51±1.74
C3 0(S)
(1.078-7.302) (2.53-52.12)
23.07±2.48 53.99±2.17
C4 0(S)
(3.5-60.64) (7.33-118)
S: Significant difference at P<0.05
Table (3.2 ) Descriptive analysis of serum Complement C3 and C4 levels two dose of vaccines
Parameter Control Dose (1) Dose (2 ) P value
C3 Mean± 3.19±0.29 21.38±2.8 5.64±0.41 0(S)
SE
Range 1.078-7.302 4.03-52.12 2.53-13.78
C4 Mean± 23.07±2.48 56.18±1.9 51.79±3.89 0(S)
SE 4
Range 3.5-60.64 28.77- 7.33-118
92.64
S: Significant difference at P<0.05
4. Discussion
The complement system is soluble glycoproteins, a part of the innate immune system was discovered
by Jules Bordet (1895) as a heat-labile component mainly produced by produced by hepato-cytes and
circulating in the extracellular fluid and blood [22] which play as anti-inflammatory roles for rapidly
recognizing and clearing pathogens, apoptotic cells and cellular debris also a dominant participant in
antibody-mediated pathogen killing , clearance and contributes to directing activation the adaptive
response[23]
The result of present study is nearly similar to Mellors et al.,(2020) [24] they proved vaccination by
the inactivated virus (Sinopharm ) vaccine ability to induce the complement component C3 and C4 in
human vaccinated compared with non-vaccinated ,specially C3 activation were observed high level in
the lung as early as 1 day after covid-19 infection or first vaccination .Furthermore, Aschenbrenner et
al.,(2021) [25] who they proved that the complement protein C3 and C4 are significantly increased in
total vaccinated groups when compared with healthy control after covid-19 Vaccine dose ,
particularly high concentrations of C3 in plasma the highest level of all complement factors in first
dose compare to C4 concentration [26] . Also , study of Pisanic et al.,(2020) has demonstrated that all
vaccinated and recovering people had significantly increased spike-specific Abs of diverse Ig isotypes
with complement component C3 and C4 in human after mRNA (Pfizer) COVID-19 vaccine [27].
On the other hand the result of present study is in agreement with Zinellu et al., (2021) [28] who
indicated that C3, C4 complement levels were significantly lower in COVID-19 patients compare with
control group similar to Dheir et al., (2020)in his study showed there is no significant difference to
complement levels of C3 and C4 protein in COVID-19 patients[29]. .
Alternative pathway that occurs by spontaneous activation of C3 activation during the first week of
COVID-19 infection where C3 attaches to the surface of viruses and may be carried intra-cellularly ;
however, the ability of viruses to cleave C3 may affect host antiviral responses [30]. This may explain
the findings of our results of the study, as it confirmed that the increase in the concentration of C3
because it is one of the direct activity of Alternative pathway of after entering the COVID-19 vaccine,
which leads to an increase in the level in the first dose , and the increase in activity may lead to the
consumption and lower levels of C3 in the second dose, which facilitates the activity of other
complement methods that depend on the concentration of C4 levels (involved in classical and MBL
pathways) as the response of complement system activity after infection and vaccine varies from one
person to another. all three pathways leads to C3 protein activation and subsequent C5 activation, This
involves protein cleavage into the activated C3a and C5a subunits, which play a major role in pro-
inflammatory responses and recruitment of immune cells. The C3b cleavage product can adhere to
pathogens, tagging them for uptake and degradation (phagocytosis) by C3b receptors on immune
cells[31,32].
The complement system is part of the innate immune system that enhances the clearance of antibodies
(Ab) , phagocytes, stimulates inflammation, and attacks the cell membranes of pathogens[33] . Also,
can neutralize non-enveloped or enveloped viruses in situation of virus infection , Following Covid-19
infection, macrophages are induced by the complement system to produce pro-inflammatory cytokines
like IL6 and IL-1b [34].
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CENTRAL ASIAN JOURNAL OF MEDICAL AND NATURAL SCIENCES

Volume: 04 Issue: 04 | Jul-Aug 2023 ISSN: 2660-4159

Complement System Response of Vaccinated Individuals with

273 Published by “ CENTRAL ASIAN STUDIES" http://www.centralasianstudies.org

274 Published by “ CENTRAL ASIAN STUDIES" http://www.centralasianstudies.org

Figure -1- Complement activation with COVID-19 patients.

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Figure.3.3. Standard curve for human C3 by ELISA

Figure.3.2. Standard curve for human C4 by ELISA

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