Efficacy of Different Vaccines in Preventing Covid-19: Retrospective Cross-Sectional Study

Assessment of the Occurrence of Viral Infection after Vaccination

Regarding the possibility of occurrence or not of viral infection after the first dose of the different vaccine protocols, it was possible to classify the participants into 4 initial groups, corresponding to the scheme shown in Table 1.

Then, to verify the possibility of occurrence or not of viral infection after the second dose of the vaccination schedule, the 150 research participants were reclassified and analyzed for the occurrence or not of COVID-19 after this process. For this stage, all participants who received the same immunogen in both doses were selected, and these results are shown in Table 2.

* With no significant difference in the percentage of infected, in the different vaccine protocols. Table 2: Distribution of research participants regarding the type of immunogen received, with no change of type in the first two doses of the vaccine schedule and the occurrence of COVID-19 after this process.

Finally, an evaluation was prepared based on the third dose received, seeking to show what was the vaccination pattern of the 7 remaining patients who, even after receiving the third dose, acquired COVID-19, allowing to observe that of these, 5 (71.43%), regardless of the vaccination schedule of the first 2 doses, received the third dose of the Pfizer vaccine, while 1 (14.28%) had received Coronavac as the third dose and the same amount (14.28%) had received AstraZeneca.

By carrying out a careful analysis of the results presented in tables 1, 2 and in the paragraph above, a ranking of “failure” in inducing protection of vaccines against COVID-19 was created, by compiling the patients who became infected, based on the last dose that was applied to the participants, before they were infected, allowing to expose a lower overall protective efficacy of the Pfizer vaccine, as shown in Table 3.

*With no significant difference in the percentage of infected, in the different vaccine protocols. Table 3: Sum of patients who tested positive for COVID-19 based on the last dose of vaccine received.

The trend of lower efficacy of the AstraZeneca and Pfizer vaccines may be related to the fact that, although the use of a viral vector or messenger RNA allows for the induction of high antibody titers, these are directed exclusively to the S protein, which has been target of most studies with vaccines that use these technologies, given their important role in the invasion process, but flaws or gaps in this process can culminate in possible oscillations of immunogenicity over time. The trend of lower effectiveness of the Pfizer vaccine proposed here corroborates the results of previous studies, including those from a prospective longitudinal study developed by Levin EG, et al. [14]. These authors followed 4686 participants who were immunized exclusively with the aforementioned immunotherapy and showed a large production of antibodies at the beginning of the post-vaccination period, but a substantial drop in the humoral response to protein S over the course of a few months, probably being a base factor for explain that, although vaccination coverage has increased in the country where the research was carried out, there was an increase in the number of incident cases, without, however, negatively influencing protection against hospitalization and death.

Another factor that may explain the possible lower efficacy of the Pfizer vaccine concerns the nature of its composition, which, as already mentioned, is messenger RNA. Such a molecule is capable of inducing host cells to produce the antigen of interest in large quantities, but it is liable to suffer instabilities that can lead to both a decrease in immunogenicity and unpredictable adverse reactions, thus implying the demand for technological investments aimed at to improve the stability and delivery of viral mRNA and thus ensure greater effectiveness of this vaccination method. With regard to AstraZeneca, a complementary factor that may explain the partial loss of efficacy concerns the possibility that some individuals may already have a previous memory immune response against the viral vectors used. According to Li M, et al. [15], although adenoviruses are not easily neutralized by pre-existing immunity, high titers of neutralizing antibodies have already been evidenced in significant portions of populations in Asia, reaching 80% in Kenya and these pre-existing antibodies Existing adenoviruses may reduce the immunogenicity of such vaccines.

However, it should be noted that, if only the borderline dose between immunization and infection is taken into account, the evidence presented in table 4 allows us to hypothesize that the vaccine from the Janssen laboratory, which also uses a viral vector that encodes the production of protein S, was the only one that induced greater protection for participants, since all patients who were at some point immunized with such an immunogen did not test positive for COVID-19. Such evidence may possibly be related to the type of viral vector used to compose this vaccine or to other genetic engineering tools that may have better targeted the delivery of viral genetic material to the host cell. As already mentioned, depending on the adenovirus used to carry the genetic information, some disadvantages may or may not occur, among which the possibility of pre-existing immunity to the vector, which can reduce vaccine efficacy, and, in another way, through tools of genetic engineering, viral vectors can be pseudotyped and genetically modified to maximize and direct the delivery of genetic material preferentially to specific cells, such as antigen-presenting cells, which would provide greater effectiveness in generating a more efficient immune response and lasting [16].

Another important factor that may explain the results presented in the present work is related to several scientific evidence, according to which SARS-Cov-2 does not only use protein S as a way of interacting with the host’s cells to achieve the infection, and such vaccines may not prevent the virus from using other strategies to circumvent the initial blockade of the S protein [15, 17]. In fact, protein S is one of the structural proteins of the virus and is of great importance in protecting the inner RNA and forming the outer particles of SARS-Cov-2, being a transmembrane glycoprotein that literally forms “nails” on the surface of the virus. , some of which extend to and bind to angiotensin-converting enzyme 2 (ACE-2), allowing invasion of the host cell.

However, there are other viral proteins that exert important interactions that are fundamental for the success of viral invasion, such as the N protein and the M protein. According to Peng XL, et al. [18], the N protein is the only protein that forms the nucleocapsid, which has as its main function to maintain the stability of the RNA within the viral particle, being very immunogenic and also considered essential for the invasion of SARS-Cov-2. Otherwise, Zambalde EP, et al. [17], demonstrated that the M protein, which is the most abundant structural protein of SARS- Cov-2, can interact with the N and S proteins, in order to maximize their functions during the invasion process, and interacts with the nuclear antigen. Proliferation in human cells, resulting in a manipulation of cellular metabolism that favors viral replication.

Therefore, the considerable effectiveness of Coronavac, which within the sample spectrum of the present study, behaved more promisingly than two of the other three vaccines evaluated (AstraZeneca and Pfizer) may be related to the fact that of the 4 vaccines, only this one has in its composition the whole and inactivated virus, and, thus, its effectiveness can be visualized, in immunological terms, through the induction of antibodies potentially capable of recognizing and inactivating other antigenic targets, in addition to the S protein, such as the N proteins, E and M [15, 17].

Analysis of the Profile of Antibodies Produced After Starting the Different Vaccination Protocols

In order to comparatively evaluate the effectiveness of antibody production of Coronavac (inactivated virus) and other vaccines (viral vector and mRNA), the results were computed only for patients who received the three doses of Coronavac (Coronavac group), which totaled 14 participants (9.33% of a total of 150 participants) of which 13 (92.85%) produced anti-S IgG and 11 (78.57%) produced anti-S IgG and anti-N IgG, attesting that , among this group, Coronavac was significantly efficient in achieving the objective that the vaccine was originally proposed for, since by using the inactivated virus there would be an induction of production of antibodies capable of neutralizing two or more antigenic targets of the virus, which would maximize the possibility of protection of the immunized, it is worth noting, however, that the antibody detection method used in the present work is a rapid immunochromatographic test that does not allow measuring the amount of antibodies produced.

Still in relation to the Coronavac group, regarding the production of anti-S IgG, 10 of the participants (71.42%) who produced such an antibody were not affected by COVID-19, and two possibilities can be inferred: a) Coronavac induced production of sufficient anti-S IgG to provide protection against future infection and b) Coronavac induced moderate or low production of anti-S IgG and the patient had no future contact with the virus. Another important data obtained in the present study concerns the fact that 3 (23.07%) of the 13 participants who took only Coronavac mentioned that before receiving the first dose they had been infected with the virus, and thus had COVID-19 before to be vaccinated, raising the possibility that the production of IgG anti-S and IgG anti-N may have been a consequence of either the previous infection or the immunization after the initial infection.

Still in relation to the Coronavac group, one of the patients showed a totally atypical behavior, since, even having been affected by COVID-19 and receiving 3 doses of the aforementioned vaccine, he was not able to produce either anti-S IgG or anti-N IgG. . It should be noted that this is a patient over 75 years of age who, due to his advanced age, already suffers from a tendency to immunological “lapse”, which characterizes immunosenescence. According to Leal AS, et al. [19] when considering general immunological aspects, senescence has been summarized as the progressive loss of homeostasis, translated by the progressive decrease in the ability of senile individuals to build immune responses in infectious processes. According to Barbosa EL, et al. [20], it can be understood that senescence in the face of COVID-19 leads to a state of greater vulnerability of the immune system, thus weakening the aged organism even more.

With the involvement of several immunological factors in the aged organism, when there is contact with the SARS- CoV-2 virus, due to the immunological fragility resulting from aging, it is possible to potentiate the reduction of the epidemiological heterogeneity for COVID-19, causing low antibody production.

Also by analyzing the results obtained, it was possible to classify a second group of participants (Coronavac Mix), who did not have COVID-19 before the first dose or during treatment, and who, for these, were recommended a vaccination schedule with two doses of Coronavac and a third booster dose composed of vaccines of another composition, regardless of the technology used, as long as it was not similar to the one that uses the exclusively attenuated virus. In this group it was observed that all patients (100%) were able to produce anti-S IgG, a portion that was practically similar to that which was able to produce this antibody in the group that received only Coronavac in the 3 doses (Coronavac group). It is important to highlight that in the present study, a qualitative assessment of the production of antibodies was carried out, not allowing to infer discussions about the magnitude of the humoral response, but based on scientific evidence published by other researchers, among which Vargas L, et al. [21], the importance of administering a third dose of vaccine when using Coronavac exclusively is justified, since, according to these authors, after only two doses of this immunogen, the induced immune response would not be quantitatively significant, resulting in a possible fruitless immunization, despite its ability to induce an immune response capable of neutralizing two or more antigenic targets of the virus.

This Coronavac vaccine bottleneck was confirmed by the aforementioned researchers, since, in their research carried out in Chile, they showed that the third dose of this vaccine induced a 6-fold increase in anti-S IgG titers, this value being significantly lower than that observed when the vaccine was administered. Application of the third booster dose using other immunobiologicals, which, according to these authors, induced about twice the increase in anti-S IgG titers in relation to the titer observed after boosting with Coronavac. Such evidence is explained by Li M, et al. [15] according to which vaccines that use the whole inactivated virus as an immunogen, despite being able to induce a greater range of antibodies against more antigens, may possibly imply a more quantitatively limited spectrum of immunity induction, due to the fact that the virus is killed. , and consequently unable to replicate and proliferate, thus not inducing a memory immune response quantitatively sufficient to quell a future infection.

An explanation for this discrepancy concerns the fact that the other vaccines evaluated in the present work use recombinant material or viral vector technology, which implies that their effectiveness is evaluated only through the production of IgG antibody against protein S, However, with some important advantages, mainly because they are capable of inducing the host cell to produce the antigen of interest (the S protein itself), triggering a specific and amplified response to the target antigen, this amplitude being greater than that induced by the virus. Inactivated, since in this type of vaccine the amount of antigen is limited to that which was inoculated, with no production of greater antigenic load in the organism, which at first could culminate in a greater possibility of risk of successful infection in immunized individuals exclusively with Coronavac. Finally, this is an observational study rather than a clinical trial, and, therefore, the effectiveness of the four types of vaccines cannot be directly compared, being necessary the design of future clinical studies that allows a more precise comparison of the effectiveness of the referred immunogens.