Covid vaccines produced by Pfizer/BioNTech use mRNA technology. According to the characteristics of vaccine, the minimum time needed to obtain full immunity after the second dose for the Comirnaty vaccine is 7 days. Onset of protection observed approx. 14 days after vaccination. Clinical trials have shown almost 95% of effective in preventing COVID-19 in people without prior infection. After the first dose, the effectiveness of the preparation was estimated at approx. 52%15. How long immunity induced by SARS-CoV-2 infection remains unclear at this stage, but antibodies are expected to last for least six months (as in the case of a COVID-19) to potentially several years. There is also insufficient information on protection against the emerging new variants of coronaviruses.
In this study, we analysed the elements of the immune response primarily in vaccinated (seropositive and seronegative) individuals and compared them with determinants of immunity in convalescents (vaccinated and unvaccinated). The basic determinant of immunization as a result of disease or vaccination in our study was the analysis of the humoral response expressed by the concentration of IgG antibodies against the S protein of the SARS-CoV-2 virus. The purpose of this analysis was to screen the primary immune response and thus cross-sectional analysis of the dynamics of B cell responses in each of the 16 compared patients groups. In the second stage, the activation of T lymphocytes was analysed in selected people (in 3 representative groups). Based on the obtained results, a high degree of heterogeneity of immune responses was found. After vaccination, the parameters of the humoral response were measurable in all probands, which confirmed the effectiveness of the mRNA vaccine in activating B lymphocytes to produce antibodies and T lymphocytes to secrete gamma interferon. Additional assessment of the cellular immune response (detection of interferon gamma, including the determination of pathogen-responsive T-cell activity), confirmed post-vaccination and post-covid immunization at the cellular level in all subjects. The response was variable, but we did not observe such wide differences as in the case of neutralizing antibodies.
Primary humoral immunity, one of the indicators of which is the presence of IgG antibodies, appeared 2 weeks after receiving the mRNA vaccine in 66.8% of people vaccinated with the first dose of Comirnaty, and after 3 weeks in all 11 people in our study group. Researchers working on the clinical trials for the Comirnaty vaccine observed a vaccine effectiveness of 52% between the time of the first and second doses, which is a 21-day period. Based on independent UK studies, it is estimated that the Pfizer/BioNTech vaccine may be more effective after the first dose than previously thought. In this study, it was observed that the effectiveness of the first dose of the vaccine 15 days after receiving it was actually closer to 89 to 91 percent16. Researchers University of Sheffield and University of Oxford, in cooperation with the UK Coronavirus Immunology Consortium (UK-CIC), tentatively conclude, based on observational studies conducted in the UK, in which healthcare workers were vaccinated against COVID-19, that the first dose of the vaccine may provide immune protection against a severe course of COVID-19. The study was conducted on a group of 237 people, some of whom had previously been infected with SARS-CoV-2, and some had never suffered from COVID-19. Above mentioned researchers, similar to our observations, obtained the strongest immune response in those who had have been infected SARS-CoV-2 before vaccination. After one dose of the Pfizer/BioNTech vaccine, the levels of T-cells in the plasma clearly increased compared to the levels seen in people who had been vaccinated but previously uninfected to coronavirus17.
Based on the concentration of anti-SARS-CoV-2 antibodies, it was found that patients who experienced symptomatic SARS-CoV-2 infection, both after receiving the first and second doses, regardless of the week of vaccination, have significantly higher antibody titer compared to seronegative people. Our observations are consistent with studies Angyal et al.17, who published data showing that in people who got vaccinated after contracting COVID-19, antibody responses after the first dose of Pfizer/BioNTech vaccine were 6.8 times higher, and T cell responses 5.9 times higher than in people who had never had the disease before. In contrast, among those who did not get sick but received a single dose of mRNA vaccine, the level of protection was similar or higher than that observed after natural infection. These researchers also did not find any correlation between age and the intensity of the humoral or cellular response. Our observations are consistent also with the results published by Krammer et al.18 and Saadat et al.19. Both our and available studies show that the titre of antibodies in seropositive people after the first dose of the vaccine is about ten times higher than in vaccinated people who have never had the disease. Based on these results, one can assumed that a prior SARS-CoV-2/COVID-19 infection triggers the immune system to a very strong response to a single dose of COVID-19 vaccine. The first dose of the vaccine, given in to people whose immune systems are already stimulated by the natural infection, has a similar effect as when given as a second 'booster' dose. Moreover, administration of the second dose of the vaccine in seropositive persons does not significantly increase the antibody concentration in these individuals. Confirmation of these observations could constitute a premise for the optimization of the vaccination program, in which decisions about taking vaccine doses should be based on the analysis of primary indicators of immune immunity. Another important aspect pointed out by Krammer et al.18 is that taking first dose of mRNA vaccines by seropositive people could protect people formerly suffering from COVID-19 from the negative effects of taking the second dose of the preparation (these people suffer the most from the second dose). It appears that the added benefit of delaying or eliminating the second dose in highly immunized individuals would also be to increase the distribution of vaccine stocks among multiple individuals. Nevertheless, this approach requires further research including the analysis of factors influencing overall immunity or vaccine efficacy. Current FDA recommendations recommend adherence to a dosing schedule that has been tested in clinical trials20.
The group of SARS-recovered patients included both those with high serum levels of antibodies and those whose IgG titre may suggest a loss of immunity acquired after COVID-19, and thus indicate the need for vaccination. Antibody levels below < 35.2 BAU/ml (negative or uncertain result) were detected in symptomatic convalescents (10 patients) who had been ill 5–6 months prior to serological examination. This observation in accordance with the reports contained in ECDC Technical Report21. The currently available results of cohort studies confirm that the protective effect of natural SARS-CoV-2 infection ranges from 81–100%, begins on day 14 after infection, and lasts for a period of five to eight months21, 22. Unfortunately, relatively low titers of IgG antibodies were also determined in 5 asymptomatic survivors after a period of several weeks after the positive test results, which may indicate a high risk of viral reinfection. People who have had COVID-19 should be vaccinated to ensure long-term and strong immunity. Chia et al. 23, noted that in convalescents group it is possible to distinguish five different patterns of the dynamics of neutralizing antibodies, and their modelling may influence the prediction of individual immunity longevity in convalescents, and thus the decision to vaccinate within this group of patients. Persistence of neutralizing antibodies in SARS-recovered related to the severity of the disease (we also observed this relationship in our study) and the sustained levels of proinflammatory cytokines, chemokines and growth factors. Chia et al.23 also observed that despite the different dynamics of neutralizing antibodies in the different groups, the T-cell responses were similar. Therefore, it seems likely that analogous dynamics of the humoral and cellular responses may also apply to the post-vaccination immune response.
Our research results shows that in convalescents the humoral immune response induced by natural infection is significantly enhanced by a single dose of vaccine, and vaccination significantly improves the extent of the immune cell responses that appear after infection. Moreover, studies by Angyal et al.17 show that the first administration of the vaccine strengthens the cellular response, as well as in vitro it strengthens the neutralizing properties in relation to the variant B.1.351 (South African). This aspect is pointed out by Skelly et al.24, who tested the neutralization strength of antibodies resulting from natural SARS-CoV-2 infection and immunization with the Pfizer/BioNTech vaccine. They noted that there is a difference in the humoral (decreased neuralization) and, to a lesser extent, cellular responses to variants of the B1.1.7 (UK) and B1.351 lines. The authors attribute these differences to the strength of the homotypic antibody responses. Thus, it is speculated that the new SARS-CoV-2 variants may avoid the protective neutralizing responses resulting from natural infection, and to a lesser extent immunization. Hence, as the authors emphasize, there is a need to induce a vaccine immune response.
In the serological test, 3 people patients had significantly lower IgG anti-SARS-CoV-2 antibodies compared to the other vaccinated persons, the level of IgG antibodies (78-106.02 BAU/ml). Based on these results, it can be concluded that these people have not acquired significant humoral immunity and may still be at risk of coronavirus infection despite vaccination. Hence the need to conduct special serological surveillance in people aged 65 + and/or people with coexisting chronic diseases, and perhaps to consider the need to take further doses of the preparation ensuring protective properties. Worrying is also the fact of confirmed cases in 3 despite vaccination, high rates of cellular and humoral responses. However, no variant of the virus has been identified that overcame the immune response mechanisms in these individuals. SARS-CoV-2 infections and vaccine infections have been reported sporadically25, 26, but raise important issues regarding the duration of immunity after natural infection and the extent of protection after vaccination, as well as the transmission of the virus by these individuals.
Testing the concentration of antibodies to S protein in both convalescents and vaccinated patients enables the analysis of the course of the humoral immune response in COVID-19. Quantitative testing of anti-SARS-CoV-2 IgG antibodies allows to determine whether the patient has responded to vaccination, and if so how intensely. It also enables the assessment of the humoral immunity acquired after undergoing SARS-CoV-2 infection. By testing anti-SARS-CoV-2 antibodies, it is possible to determine the concentration of antibodies that provide protection against infection, as well as to make rational decisions about booster doses of COVID-19 vaccines. The greatest benefit of the research is the ability to quantify the acquisition of humoral immunity to SARS-CoV-2 as a result of coronavirus infection and/or vaccination. Antibody testing is not required in the context of vaccination, but knowledge of the immune status before and several weeks after the last dose of vaccination may nevertheless allow inferring the immune response to immunization and provide an indication of the degree of immunity obtained against COVID-19. Due to the lack of data on the persistence of immunity acquired as a result of a vaccine reaction, it is also important to monitor the level of antibodies over time (especially among healthcare professionals, people over 65 years and chronically ill), as the future may also indicate the need (or lack thereof) taking a booster dose. The results of the conducted research could be useful in the future for the development of new recommendations of the vaccination program, hence the need to continue them on a larger scale. The diversity of immune responses shows the need for research, the inherent element of which will be immunological monitoring of the durability of disease resistance or protection against its severe course in vaccinated people and/or susceptibility to reinfection in COVID-19 convalescents. By analysing the level of antibodies, it is possible to identify people who are already immunized as well as people who have not acquired immunity as a result of vaccination, and those who may have lost the acquired immunity after contacting SARS-CoV-2. It seems that such a test should be an integral part of the assessment of immunological parameters, especially before making an informed decision about vaccination or its delay in convalescents, as well as the assessment of the durability of immune protection, important from the perspective of making a decision to take booster doses a few months after the initial administration of the vaccine against COVID-19.