Immunogenicity Induced by COVID-19 Vaccines in Mexican Population: mRNA Expression for IgG Anti-spike
Conditions: COVID-19 Vaccine
Sponsor: National Polytechnic Institute, Mexico

 
    NATIONAL POLYTECHNIC INSTITUTE 
 
SUPERIOR SCHOOL OF MEDICINE 
          
GRADUATE STUDIES AND RESEARCH SECTION 
 
 
 
                              
 
 
 
 
Immunogenicity induced by COVID-19 vaccines in Mexican population: 
mRNA expression for IgG anti-spike. 
 
 
 
Principal clinical researcher 
PhD Modesto Gómez López 
PhD Nadia Mabel Pérez Vielma 
 
Clinical sub investigator 
Master’s degree Jennifer Viridiana Sánchez Camacho 
Dr. Claudia Mariana Andrade Torres 
Dr. Miriam Azucena Delgado Hernández 
 
 
Mexico City, CDMX, July 10, 2021 
 
 

 
2 
Immunogenicity induced by COVID-19 vaccines in Mexican population: 
mRNA expression for IgG anti-spike. 
 
Introduction: 
 
In December 2019, health authorities in Wuhan, Hubei province, China issued an 
epidemiological alert for an outbreak of pneumonia of unknown causes, the infected 
patients had in common having visited a local seafood and wild animal market1. 
 
At the beginning of the outbreak, samples from seven patients with severe 
pneumonia in the intensive care unit (ICU) of Wuhan Jin-Yin-Tan Hospital were 
obtained for analysis by the Wuhan Institute of Virology (WIV) to isolate the pathogen 
causing the disease. After studying the samples received, the WIV identified a new 
coronavirus as responsible for the outbreak, which shares 79.6% similarity to the 
genomic sequences of SARS-CoV and 96% similarity to those of a bat 
coronavirus.2,3 Based on the phylogenetic and taxonomic characteristics of the virus, 
the International Committee on Taxonomy of Viruses officially named the newly 
detected virus; severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-
2)4 and the disease caused by this virus has been termed; Coronavirus disease 2019 
(COVID-19), an extremely contagious respiratory infection.5 
 
In an attempt to contain the epidemic, the Chinese government took a series of 
measures to prevent the displacement of millions of people inside and outside the 
country; however, many of them have already left the country to go on vacation to 
other places to celebrate the traditional Chinese New Year.6 On January 30, 2020, 
the World Health Organization (WHO) announced that the SARS-CoV-2 pneumonia 
outbreak was a global health emergency7 and on March 11 declared the disease 
COVID-19 a pandemic.8 As of August 26, 2021, 213,752,662 confirmed cases and 
4,459,381 deaths have been reported worldwide; in Mexico, 3,291,761 total cases 
and 256,287 total deaths due to COVID-19 have been reported.9 For this reason, 
the WHO has created a database containing the results of research on COVID-19 

 
3 
conducted by scientists and health professionals from around the world, which has 
allowed accelerating the processes of diagnosis, treatment and vaccine 
development.10 
 
According to the information provided by WHO, it is vital to continue research to 
answer a number of questions about the vaccines currently in use, which have been 
licensed for emergency use to combat the COVID-19 pandemic. One of the most 
worrisome questions concerns the duration of the immunity conferred by these 
vaccines and, moreover, whether they will protect the population from the new 
SARS-CoV-2 strains that continue to appear. 
 
General description of coronaviruses 
 
Coronaviruses (CoVs) belong to the Coronaviridae family and consist of an envelope 
and a single strand of positive-sense, non-segmented ribonucleic acid (RNA). The 
genomic organization of all CoVs is similar; the non-structural proteins are encoded 
within the two thirds of the 5' end and the structural proteins called; spike (S), 
envelope (E), membrane (M) and nucleocapsid (N) are encoded in the 3' third.5,11 
The name coronavirus is due to the characteristic crown-like appearance of the 
virions, this morphology is given by the spike-shaped proteins embedded in the 
envelope.12 Based on their phylogenetic properties, CoVs are divided into four 
genera; group 1 (alpha-CoV), group 2 (beta-CoV), group 3 (gamma-CoV), group 4 
(delta-CoV).13 
 
This family of viruses has been known since the 1930s, they were identified as 
pathogens responsible for infectious diseases in farm animals, and they are also 
responsible for diseases in a wide variety of animals including humans.14 
 
Before SARS-CoV-2 appeared, six species of coronaviruses were already known to 
cause disease in humans, four of which cause mild symptoms of the common cold 
in non-immunocompromised individuals. The other two strains are of zoonotic origin; 

 
4 
SARS-CoV, responsible for outbreaks of severe respiratory syndrome in 2002 and 
2003, and MERS-CoV, which caused severe respiratory illness in the Middle East in 
2012.15 
 
Genomic structure of SARS-COV-2 
 
The structural proteins of SARS-CoV-2 play a key role in the interaction of the virus 
with host cells. The S protein consists of two subunits, S1 and S2. The S1 subunit 
contains the receptor binding domain (RBD) that binds to the host cell receptor, while 
the S2 subunit facilitates fusion of the viral envelope with the cell membrane. 
Angiotensin converting enzyme type 2 (ACE-2) has been identified as the main 
receptor for SARS-CoV-2, this receptor is predominantly expressed on type II 
pneumocytes, airway epithelium, digestive tract, endothelium, kidney, fibroblasts, 
and various immune cells.16-19 The M protein confers structure to the virus, once 
bound to the nucleocapsid it regulates virus assembly, and also contains T-cell 
epitopes that trigger the production of neutralizing antibodies in infected individuals. 
The E protein is essential for the assembly, release and pathogenesis of the virus. 
The N protein is key in the formation of complexes with the viral genome, enhances 
the functions of the M protein and increases viral replication.20 
 
COVID-19 
 
COVID-19 is defined as the disease caused by the new SARS-CoV-2 coronavirus. 
The main mechanism of transmission is by the airborne route through contact with 
flung droplets and aerosols that are released by an infected person when talking, 
coughing or sneezing, especially in crowded, closed and poorly ventilated places.21-
25 Other means of spreading the virus are: contact with objects or surfaces containing 
the virus, constant touching of the face (eyes, nose or mouth) as well as shaking 
hands with an infected person.26 
 

 
5 
The incubation period varies between 5 and 7 days. The clinical presentation is not 
specific; it can range from asymptomatic to extremely severe. The most common 
symptoms are fever, nonproductive cough, muscle pain, fatigue and dyspnea; some 
patients may also present with headache, nausea and diarrhea, especially early in 
the course of infection, prior to the onset of fever. Recent studies indicate that the 
severity of the disease correlates with age (> 60 years) and with the presence of 
underlying diseases (hypertension, diabetes, heart disease); these groups of 
patients are at higher risk of developing acute respiratory distress, pneumonia and 
even death.22,27,28 Several tests are currently available for the diagnosis of COVID-
19, but the reverse transcriptase polymerase chain reaction (rt-PCR) test is the gold 
standard diagnostic technique.29,30 
 
Vaccines and COVID-19 
 
To date, there is no specific treatment for COVID-19.31 For this reason, efforts have 
focused on preventing the spread of the disease through mitigation measures and 
on seeking herd immunity, also known as flock immunity, through vaccination.32,33 
Research conducted after the SARS-CoV epidemic in 2003 has laid the groundwork 
for the development of vaccines against COVID-19, due to the genetic similarity 
shared by both CoVs.34 
 
Historically, the implementation of vaccination programs, especially during 
childhood, has been the key to controlling and/or eradicating countless infectious 
and contagious diseases. Vaccines prepare the immune system to create 
immunoglobulins that can later recognize the pathogen in question and attack it, thus 
breaking the chain of disease transmission.35,36 
 
As of June 3, 2021, WHO has assessed that the following COVID-19 vaccines meet 
the criteria of safety and efficacy for population use.37 
 
 

 
6 
Based on viral vectors 
 
- Oxford/AstraZeneca (ChAdOx1 nCoV-19) 
It is a vaccine that uses the chimpanzee adenovirus ChAdOx1 as a vector, 
expressing the S protein of SARS-CoV-2. According to data provided by the WHO 
and other studies, the vaccine has an efficacy of 63.09% against symptomatic 
SARS-CoV-2 infection. It is recommended to apply two doses of 0.5 ml each by 
intramuscular route with an interval of 8 to 12 weeks. It was authorized by the Federal 
Commission for Protection against Sanitary Risks (COFEPRIS) on January 4, 2021 
for use in Mexico.38-41 
 
- Janssen (Ad26.COV2-S) 
This is a single-dose vaccine using a non-replicating adenoviral vector of serotype 
26 containing the S protein of SARS-CoV-2. Phase 3 results published by 
Johnson&Johnson Pharmaceuticals indicate that the efficacy of the Janssen vaccine 
against moderate to severe COVID-19 infection was 72% in the United States of 
America, 66% in Latin America and 57% in South Africa 28 days after inoculation. 
The WHO Strategic Advisory Group of Experts (SAGE) recommends a dose of 0.5 
ml administered intramuscularly. COFEPRIS authorized its use in Mexico on May 
27, 2021.41-44 
 
Based on nucleic acids 
 
- Pfizer BioNTech (BNT162b2) 
This vaccine contains the mRNA coding for the S protein of SARS-CoV-2. According 
to the results of a multinational trial to assess the efficacy and safety of BNT162b2, 
it was concluded that after administration of two doses of 0.3 ml respectively 21 days 
apart, the efficacy was 95% against symptomatic infection caused by SARS-CoV-2 
in persons older than 16 years of age. WHO recommends administering two doses 
21 to 28 days apart, COFEPRIS authorized its use in Mexico on December 11, 
2020.41, 45, 46 

 
7 
 
- Modern (mRNA-1273) 
Like the previous one, it contains the mRNA encoding the S protein of SARS-COV-
2 encapsulated in lipid nanoparticles. Phase 3 trials for the mRNA-1273 vaccine 
showed 94.1% efficacy in preventing severe COVID-19 infection that can be 
observed after day 14 of the first application. WHO recommends the use of two 
doses of 0.5 ml each with an interval of 28 days. In Mexico, its use was authorized 
by COFEPRIS on August 17, 2021.41,47,48 
 
Based on inactivated viruses 
 
- Sinovac (CoronaVac) 
It is a vaccine formulated based on incubation of SARS-CoV-2 (CN02 strain) in Vero 
cells. A Phase 3 trial conducted in Turkey tested the efficacy and safety of this 
vaccine in volunteers between 18 and 59 years of age. The double-blind, 
randomized, placebo-controlled study concluded that the vaccine confers good 
humoral response against SARS-CoV-2, as well as high efficacy against 
symptomatic COVID-19 confirmed by PCR. It reports 51% efficacy against SARS-
CoV-2 infection, 100% efficacy against severe infection and 100% efficacy against 
hospitalization from day 14 after receiving the second dose. The SAGE recommends 
applying two doses of 0.5 ml intramuscularly with a separation of 2 to 4 weeks 
between the first and second dose. In Mexico, COFEPRIS authorized its use as of 
February 9, 2021.41,49,50 
 
- Sinopharm (COVID-19 inactivated vaccine, Vero cells) 
It uses the same inactivation process as Sinovac but using the HB02 strain of SARS-
CoV-2. A multi-country Phase 3 trial demonstrated 79% efficacy against symptomatic 
SARS-CoV-2 infection 14 days after the second dose. WHO recommends the 
application of 2 doses of 0.5 ml respectively, with a separation of 3 to 4 weeks 
between the first and second dose. It was recently approved by COFEPRIS on 
August 25, 2021 for use in Mexico.41, 51, 52 

 
8 
 
Justification 
 
Currently, the pandemic originated by COVID-19 continues to be a serious public 
health problem in our country (Mexico) that implies a great investment by the federal 
government to combat the ravages caused by it, so it is of vital importance to 
determine the explicit mechanisms by which the different vaccines administered in 
our population have their protective effects on the virus infection. Therefore, this 
study focuses on identifying the molecular mechanisms by which inhibitions of virus 
recognition by the human host cell are carried out. 
 
Problem Statement 
 
The precise mechanism by which a vaccinated patient has a high probability of being 
infected with a different strain of SARS-CoV-2 is currently unknown. Assuming this, 
recontagion and further increases in the rates of active cases of COVID-19 in the 
vaccinated population are not prevented. Therefore, by determining the molecular 
mechanisms of infection, therapeutic targets can be identified, and specific 
treatments can be offered to prevent infection in both first-contact subjects and those 
with a history of COVID-19 infection. 
 
Hypothesis 
Gene expression for IgG anti-spike in subjects with a complete vaccination schedule 
against COVID-19 does not develop the necessary immunogenicity in the Mexican 
population to prevent re-contagion. 
 
General Objective 
To characterize the immunogenicity induced by COVID-19 vaccines in Mexican 
population: mRNA expression for IgG anti-spike. 
 
 

 
9 
Specific objectives 
1. Determine the mechanisms of virus transmission on the cell. 
2. To identify the study population. 
3.To identify the anti-spike IgG genes in vaccinated population. 
 
Methodology 
 
Type of study, general design and population 
A quasi-experimental, longitudinal, retrolective, comparative, quasi-experimental 
study will be carried out in a Mexican population older than 18 years with a complete 
vaccination schedule against COVID-19, to determine the immunogenicity induced 
by the vaccines. 
 
Four study groups will be formed. 
• Group 1: 20 persons who have received the Oxford/AstraZeneca vaccine 
(ChAdOx1 nCoV-19). 
• Group 2: 20 persons who received the Gamaleya National Center vaccine 
(Sputnik V). 
• Group 3: 20 people who have received the Pfizer/BioNTech vaccine (BNT162b2) 
• Group 4: 20 persons who have received Sinovac vaccine (CoronaVac) 
 
Inclusion criteria: 
1.- Persons of Mexican origin. 
2.- Over 18 years of age. 
3.- With complete vaccination schedule against COVID-19. 
4.- Allowing peripheral blood samples to be taken. 
5.- To sign an informed consent form. 
6.-Who agree to participate in the protocol. 
 
Exclusion criteria: 
1.- Persons with incomplete vaccination schedule against COVID-19. 

 
10 
Persons who have 30 +/- 5 days after having completed the COVID-19 vaccination 
schedule. 
3.- People under treatment with any immunosuppressive drug. 
4.- Persons who refuse to sign the informed consent. 
 
Elimination criteria: 
1.- Subjects who during the study develop COVID-19. 
2.- Subjects who decide to leave the study before the stipulated time for the 
collection of the required blood samples. 
 
Procedure: 
(a) Participants were selected by clinical history to assess current health status, 
obtain demographic data, as well as personal pathological history of importance for 
the study (chronic degenerative diseases, history of COVID-19 disease). 
b) Peripheral venous blood samples (3 ml per occasion) will be taken from all 
participants. They will be carried out on days 30,60 and 120 after completion of the 
COVID-19 vaccination schedule. 
c) Sample processing:  
tRNA extraction from all samples. 
cDNA synthesis 
Real time PCR performance. 
 
Ethical Aspects 
The present study will strictly follow the ethical norms for research established in the 
Declaration of Helsinki, at the international level. This Declaration suggests that the 
sole purpose of research in humans should be the improvement of diagnostic, 
therapeutic and prophylactic methods, as well as the understanding of the etiology 
and pathogenesis of diseases.  At the national level, according to article 17 of the 
Regulations of the General Health Law on Health Research, this study is considered 
of minimal risk for the participants, since 3mL of blood will be taken by venous 

 
11 
puncture. Individuals who wish to participate will be asked to sign the specific 
informed consent form, after a thorough explanation of the procedure. 
The data obtained from the individuals participating in the study will be protected by 
the “Federal Law for the protection of personal data”, so the anonymity of the 
samples and the participants is guaranteed. The results of the study will be under 
the custody and responsibility of the principal investigator for subsequent analysis 
and publication in scientific journals. 
 
 
Statistical analysis 
Descriptive phase: The results were presented in tables for continuous variables with 
normal distribution in measurements ± standard deviation and for free distribution in 
medians and percentiles. While the categorical variables were presented in 
percentages and total figures. 
 
Bivariate phase: To look for differences in the quantitative variables according to the 
Kolmogorov-Smirnov normality test, the student t test or the Mann-Whitney U test 
were used or for the related ordinal variables the Wilcoxon test. The dichotomous or 
ordinal related qualitative variables were analyzed with the McNemar test, for the 
dichotomous or ordinal variables not related they were analyzed with the chi square 
test or Fisher's exact test. 
Schedule 
Stage 1 
Stage 2  
Stage 3 
Sample collection 
Experimental 
Analysis of results and re
writing. 
Duration: 4 months (Septemb
December 2021) 
Duration: 4 months (January-A
2022) 
Duration: 
3 months 
(May-J
2022) 
Collection and transport of bl
samples 
from 
all 
selec
participants. 
✓ Extraction of tRNA from bl
samples. 
✓ cDNA synthesis. 
✓ Real-time PCR. 
 

 
12 
 
Multivariate phase: To compare and find the differences in more than two groups in 
the quantitative variables with free distribution the Kruskall-Wallis test; for the related 
samples with free distribution the Friedman test was used. All calculations were 
performed using the current version of the SPSS statistical package for Windows 
and the Jamovi program version 4.1 of R. Statistical significance was considered to 
be a P value <0.05 and a confidence interval of 95%. 
 
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