Search Results (25)

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant. Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5. Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant. Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus. Full article

SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies. Full article

SARS-CoV-2 has a relatively high mutation rate, with the frequent emergence of new variants of concern (VOCs). Each subsequent variant is more difficult to neutralize by the sera of vaccinated individuals and convalescents. Some decrease in neutralizing activity against new SARS-CoV-2 variants has also been observed in patients vaccinated with Gam-COVID-Vac. In the present study, we analyzed the interplay between the history of a patient’s repeated exposure to SARS-CoV-2 antigens and the breadth of neutralization activity. Our study includes four cohorts of patients: Gam-COVID-Vac booster vaccinated individuals (revaccinated, RV), twice-infected unvaccinated individuals (reinfected, RI), breakthrough infected (BI), and vaccinated convalescents (VC). We assessed S-protein-specific antibody levels and the ability of sera to neutralize lentiviral particles pseudotyped with Spike protein from the original Wuhan variant, as well as the Omicron variants BA.1 and BA.4/5. Individuals with hybrid immunity (BI and VC cohorts) exhibited significantly higher levels of virus-binding IgG and enhanced breadth of virus-neutralizing activity compared to individuals from either the revaccination or reinfection (RV and RI) cohorts. These findings suggest that a combination of infection and vaccination, regardless of the sequence, results in significantly higher levels of S-protein-specific IgG antibodies and the enhanced neutralization of SARS-CoV-2 variants, thereby underscoring the importance of hybrid immunity in the context of emerging viral variants. Full article

The COVID-19 pandemic continues to pose a threat to global public health. The purpose of this research was to determine the epidemiological characteristics of COVID-19 in the North Bačka district while observing seven pandemic waves. The cross-sectional study was based on data from the COVID-19 surveillance database of the Institute for Public Health of Vojvodina during the period from March 2020 to December 2022. A total of 38,685 primary infections and 4067 reinfections caused by SARS-CoV-2 were notified. Pandemic waves caused by the Delta variant (cumulative incidence rate of 2482.37/100,000) and by the Omicron variant (cumulative incidence rate of 2994.45/100,000) emerged as significant focal points during the surveillance period. Over the course of three consecutive years (2020–2022), women were more affected (50.11%, 54.03%, and 55.68%, respectively). The highest incidence rates in age-specific categories were recorded in 2021 for the age group 40–49 (1345.32 per 10,000 inhabitants), while in 2022, they shifted towards the elderly population. Regarding vaccination status at the time of diagnosis, in 2021, around 15% of patients were vaccinated, while in 2022, the number increased to 37%. The most widely received vaccine was BBIBP-CorV (67.45%), followed by BNT162b2 (19.81%), Gam-COVID-Vac (9.31%), and ChAdOx1 nCoV-19 (3.42%) vaccine. The implementation of stringent public health measures and their mitigation, together with the emergence of new variants, influenced the dynamics of COVID-19 pandemic waves in the North Bačka district. Notably, throughout the study period, the working-age population was the most affected, along with females, with a mild clinical presentation dominating. Reinfections were most frequently recorded during the latter pandemic waves. Dealing with this pandemic has provided some valuable lessons for the development of future strategies in the case of a similar public health crisis. Full article

COVID-19 and other infectious diseases can exacerbate the course of paroxysmal nocturnal hemoglobinuria (PNH). The efficacy and safety of the Gam-COVID-Vac vaccine in patients with PNH has not been adequately studied. A retrospective, observational, cohort, non-comparative study was performed to assess the course of COVID-19 as well as the safety and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study included data from 52 patients with PNH aged 18 to 75 years, 38 of whom received background therapy with eculizumab (Elizaria^®) between March 2020 and January 2022. COVID-19 was diagnosed according to the results of PCR testing. The patients were divided into two groups for comparison of the incidence of COVID-19. Group 1 included non-vaccinated patients with PNH, and Group 2 included patients vaccinated prior to the onset of COVID-19. According to vaccination, patients were subdivided into non-vaccinated and vaccinated groups without signs of previous COVID-19 at the beginning of the analyzed period, and patients vaccinated half a year or more after recovery from COVID-19. Testing for anti-SARS-CoV-2 IgG levels was carried out in patients with PNH in the year after their COVID-19. Tests for anti-SARS-CoV-2 RBD IgG levels were performed on vaccinated patients. In total, 28 (53.8%) of the enrolled patients had COVID-19, including asymptomatic forms in 7 (25%) and mild forms in 16 (57%) patients. A total of 22 (42.3%) patients were fully vaccinated with Gam-COVID-Vac, of which 13 (25%) patients were vaccinated without the signs of previous SARS-CoV-2infection, and 9 (17.3%) patients were vaccinated after COVID-19. The number of patients who had COVID-19 was about two times higher in Group 1 (non-vaccinated; 24) (61.5%), whereas in Group 2 (vaccinated), the number of patients with COVID-19 was only 4 (30.8%). The proportion and number of patients who did not have COVID-19 was higher in the group of vaccinated patients (9; 69.2%) than in the group of non-vaccinated patients (15; 38.5%) (p = 0.054). In patients who had been infected with COVID-19, maximum concentrations of anti-SARS-CoV-2 IgG were observed 2–3 months after the acute infection phase, followed by a gradual decline by month 9–10. The mean RBD IgG concentration was higher in the group of patients who had been infected by COVID-19 than in the group of patients without COVID-19 (p = 0.047). Therapy type, including eculizumab, did not have a significant impact on RBD IgG titers (p > 0.05). Hospitalization was required in five (18%) patients, all of whom had breakthrough hemolysis and severe lung damage on CT scans. After the first dose, adverse events (AEs) were reported in 41% of the patients (body temperature increased in 18%; headache in 13.6%; and pain in joints in 4.5%; colitis exacerbation was observed in 4.5%). After the second dose, no AEs were reported. The performed study suggests the possible efficacy and demonstrates the safety of Gam-COVID-Vac (Sputnik V) for the prophylaxis of COVID-19 in patients with PNH who experience immunosuppression due to target therapy. Full article

Background: Limited data are available on humoral responses determined by automated neutralization tests following the administration of the three different types of COVID-19 vaccinations. Thus, we here evaluated anti-SARS-CoV-2 neutralizing antibody titers via two different neutralization assays in comparison to total spike antibody levels. Methods: Healthy participants (n = 150) were enrolled into three subgroups who were tested 41 (22–65) days after their second dose of mRNA (BNT162b2/mRNA-1273), adenoviral vector (ChAdOx1/Gam-COVID-Vac) and inactivated whole-virus (BBIBP-CorV) vaccines, with no history or serologic evidence of prior SARS-CoV-2 infection. Neutralizing antibody (N-Ab) titers were analyzed on a Snibe Maglumi^® 800 instrument and a Medcaptain Immu F6^® Analyzer in parallel to anti-SARS-CoV-2 S total antibody (S-Ab) levels (Roche Elecsys^® e602). Results: Subjects who were administered mRNA vaccines demonstrated significantly higher SARS-CoV-2 N-Ab and S-Ab levels compared to those who received adenoviral vector and inactivated whole-virus vaccinations (p < 0.0001). N-Ab titers determined by the two methods correlated with each other (r = 0.9608; p < 0.0001) and S-Ab levels (r = 0.9432 and r = 0.9324; p < 0.0001, respectively). Based on N-Ab values, a new optimal threshold of Roche S-Ab was calculated (166 BAU/mL) for discrimination of seropositivity showing an AUC value of 0.975 (p < 0.0001). Low post-vaccination N-Ab levels (median value of 0.25 μg/mL or 7.28 AU/mL) were measured in those participants (n = 8) who were infected by SARS-CoV-2 within 6 months after immunizations. Conclusion: Both SARS-CoV-2 N-Ab automated assays are effective to evaluate humoral responses after various COVID-19 vaccines Full article

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities of induced antibodies have not been fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before and after two immunizations with Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) was studied on a panel of micro-arrayed recombinant folded and unfolded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and 46 peptides spanning the spike protein (S) and by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability of Gam-COVID-Vac-induced antibodies to inhibit binding of the receptor-binding domain (RBD) to its receptor angiotensin converting enzyme 2 (ACE2) was investigated in a molecular interaction assay (MIA). The virus-neutralizing capacity of antibodies was studied by the pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 and Omicron. We found that Gam-COVID-Vac vaccination induced significant increases of IgG₁ but not of other IgG subclasses against folded S, spike protein subunit 1 (S1), spike protein subunit 2 (S2), and RBD in a comparable manner in naïve and convalescent subjects. Virus neutralization was highly correlated with vaccination-induced antibodies specific for folded RBD and a novel peptide (i.e., peptide 12). Peptide 12 was located close to RBD in the N-terminal part of S1 and may potentially be involved in the transition of the pre- to post-fusion conformation of the spike protein. In summary, Gam-COVID-Vac vaccination induced S-specific IgG₁ antibodies in naive and convalescent subjects in a comparable manner. Besides the antibodies specific for RBD, the antibodies induced against a peptide close to the N-terminus of RBD were also associated with virus-neutralization. Full article

The course of the COVID-19 pandemic has been critically altered by the availability of vaccines. To assess the risk of COVID-19 in the vaccinated, as compared to the unvaccinated population, as well as the comparative effectiveness of the BBIBP-CorV (Sinopharm), BNT162b2 (Pfizer/BioNTech), Gam-COVID-Vac (Sputnik V) and ChAdOx1 (AstraZeneca) vaccines in the prevention of clinical infection, we carried out a retrospective study of the incidence of clinical COVID-19 in the Belgrade city municipality of Voždovac among both vaccinated and unvaccinated individuals during a 4-month period between 1 July and 31 October 2021. The study included all individuals with a symptomatic infection confirmed by a positive PCR and/or antigen test. Only those who received two vaccine doses were considered as vaccinated. The results showed that of the Voždovac population of 169,567, a total of 81,447 (48%) individuals were vaccinated by the end of the study. Vaccination coverage increased with age, ranging from 1.06% in those below age 18, to even 78.8% in those above 65 years of age. More than one half (57.5%) of all those vaccinated received BBIBP-CorV, while 25.2% received BNT162b2, 11.7% Gam-COVID-Vac and 5.6% ChAdOx1. The overall risk of infection of the vaccinated vs. the unvaccinated was 0.53 (95% CI 0.45–0.61). Compared to the incidence of COVID-19 of 8.05 per 1000 in the unvaccinated population, the relative risk in the vaccinated was 0.35 (95% CI 0.3–0.41). The overall VE was 65%, differing widely among age groups and by vaccine. VE was 79% for BNT162b2, 62% for BBIBP-CorV, 60% for ChAdOx1 and 54% for Gam-COVID-Vac. The VE for BBIBP-CorV and BNT162b2 increased with age. The obtained results demonstrate a significant overall effectiveness of anti-COVID-19 vaccination, which, however, varied significantly among the analyzed vaccines, and was the highest for BNT162b2. Full article

The COVID-19 pandemic has required extensive research on the new coronavirus SARS-CoV-2 and the creation of new highly effective vaccines. The presence of T-cells in the body that respond to virus antigens suggests adequate antiviral immunity. We investigated T-cell immunity in individuals who recovered from mild and moderate COVID-19 and in individuals vaccinated with the Gam-COVID-Vac combined vector vaccine. The ELISPOT method was used to determine the number of T-cells responding with IFN-γ synthesis to stimulation by peptides containing epitopes of the S-protein or N-, M-, ORF3, and ORF7 proteins, using peripheral blood mononuclear cells (PBMCs). At the same time, the multiplex method was used to determine the accumulation of IFN-γ and other cytokines in the culture medium. According to the data obtained, the proportion of positive conclusions about the T-cell immune response to SARS-CoV-2 antigens in control, recovered, and vaccinated individuals was 12%, 70%, and 52%, respectively. At the same time, more than half of the vaccinated individuals with a T-cell response were sensitized to the antigens of N-, M-, ORF3, and ORF7 proteins not produced by Gam-COVID-Vac, indicating a high likelihood of asymptomatic SARS-CoV-2 infection. Increased IFN-γ release by single sensitized T-cells in response to specific stimulation in recovered and vaccinated individuals did not result in the accumulation of this and other cytokines in the culture medium. These findings suggest a balance between cytokine production and utilization by immunocompetent cells as a prerequisite for providing a controlled cytokine signal and avoiding a “cytokine storm”. Full article

Vaccination against COVID-19 has occurred in Russia for more than two years. According to the Russian official clinical guidelines to maintain tense immunity in the conditions of the ongoing COVID-19 pandemic, it is necessary to use booster immunization six months after primary vaccination or a previous COVID-19 contraction. It is especially important to ensure the maintenance of protective immunity in the elderly, who are at risk of severe courses of COVID-19. Meanwhile, the immunological effectiveness of the booster doses has not been sufficiently substantiated. To investigate the immunogenicity of Sputnik V within the recommended revaccination regimen and evaluate the effectiveness of booster doses, we conducted this study on 3983 samples obtained from individuals previously vaccinated with Sputnik V in Moscow. We analyzed the level of antibodies in BAU/mL three times: (i) six months after primary immunization immediately before the booster (RV), (ii) 3 weeks after the introduction of the first component of the booster (RV1), and (iii) 3 weeks after the introduction of the second component of the booster (RV2). Six months after the primary vaccination with Sputnik V, 95.5% of patients maintained a positive level of IgG antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. The degree of increase in the specific virus-neutralizing antibodies level after revaccination increased with a decrease in their initial level just before the booster dose application. In the group of people with the level of antibodies up to 100 BAU/mL six months after the vaccination, a more than eightfold increase (p < 0.001, Wilcoxon criterion with Bonferroni adjustment) in the level of specific antibodies was observed (Me = 8.84 (IQR: 3.63–30.61)). A significant increase in the IgG level after receiving both the first and the second booster doses occurred at the initial titer level up to 300 BAU/ mL (p < 0.001) in those who did not contract COVID-19 in the past and up to 100 BAU/mL (p < 0.001) in those who were previously infected with SARS-CoV-2. A significant increase in the antibody level after the first dose of the booster was noted for people who had up to 500 BAU/mL (p < 0.05), regardless of the previous COVID-19 infection. Thus, revaccination is most effective in individuals with an antibody level below 500 BAU/mL, regardless of the vaccinee age and COVID-19 contraction. For the first time, it has been shown that a single booster dose of the Sputnik vaccine is sufficient to form a protective immunity in most vaccinees regardless of age and preexisting antibody level. Full article

Many available SARS-CoV-2 vaccines demonstrated good humoral response, but studies directly comparing their immunogenicity in the general population are lacking. We evaluated the medium–term kinetics of anti-S SARS-CoV-2 antibodies (Abs) at one and six months after the second dose of BNT162b2, BBIBP-CorV, and Gam-COVID-Vac. Immunogenicity at six months was directly compared between BNT162b2, BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 nCoV-19. Participants ≥ 20 years old from Novi Sad, Serbia, without prior SARS-CoV-2 infection, were included. Anti S1/S2 IgG antibodies were measured using quantitative LIAISON SARS-CoV-2 assay. A total of 368 participants were included: 231 (62.77%) had sera collected at two time points. Two doses of BNT162b2 were received by 37.50% of participants, followed by BBIBP-CorV (22.01%), Gam-COVID-Vac (21.47%), and ChAdOx1 nCoV-19 (19.02%). Mean Ab levels at the 28th day and 6 months were 216.55 (SD = 105.73) AU/mL and 75.68 (SD = 57.30) for BNT162b2, 194.38 (SD = 140.24) and 90.53 (SD = 111.30) for Gam-COVID-Vac, and 72.74 (SD = 80.04) and 24.43 (SD = 38.43) for BBIBP-CorV group (p < 0.01, between two time points across all three groups), with a significant difference between women and men (p < 0.01, for both sexes). At the sixth month post-vaccination, the highest mean Ab level was detected in Gam-COVID-Vac group (91.28 AU/mL, SD = 95.96), followed by BNT162b2 (85.25 AU/mL, SD = 60.02), ChAdOx1 nCoV-19 (64.22 AU/mL, SD = 65.30), and BBIBP-CorV (25.26 AU/mL, SD = 36.92) (p < 0.01). Anti-spike IgG persistence was demonstrated six months post-vaccination with a significant decline in Ab levels. These results suggest a lower protection against SARS-CoV-2 over time. Our findings support the introduction of additional (booster) doses. Full article

This article provides a systematic assessment of the efficacy, risks, and methodological quality of evidence from five major publicly available vaccine trials. Results from Pfizer-BioNTech mRNA, Moderna-US NIH mRN-1273, AstraZeneca-Oxford ChAdOx1 nCov-19, Gamaleya GamCovidVac (Sputnik V), and Ad26.COV2.S Johnson & Johnson vaccines were included. Extracted benefits and risks data from each trial were summarized using the GRADE approach denoting the overall certainty of evidence along with relative and absolute effects. Relative risk reduction across all five vaccine trials ranged from 45% to 96%. Absolute risk reduction in symptomatic COVID-19 ranged from 6 to 17 per 1000 across trials. None of the vaccines were associated with a significant increase in serious adverse events compared to placebo. The overall certainty of evidence varied from low to moderate. All five vaccines are effective and safe, but suggest room for improvement in the conduct of large-scale vaccine trials. Certainty of evidence was downrated due to risk of bias, which can be mitigated by improving transparency and thoroughness in conduct and reporting of outcomes. Full article

COVID-19 booster vaccines have been adopted in almost all countries to enhance the immune response and combat the emergence of new variants. Algeria adopted this strategy in November 2021. This study was conducted to consider the self-reported side effects of COVID-19 booster vaccines by Algerians who were vaccinated with a booster dose of one of the approved inactivated-virus vaccines, such as BBIBP-CorV and CoronaVac, or one of the adenoviral-vector-based vaccines, such as Gam-COVID-Vac, AZD1222 and Ad26.COV2.S, and to determine the eventual risk factors. A cross-sectional study using an online self-administered questionnaire (SAQ) was conducted in Algeria between 28 April 2022, and 20 July 2022. A descriptive analysis of the 196 individuals who were included showed a nearly equal distribution of adenoviral- (52%) and inactivated-virus vaccines (48%) and of males (49.5%) and females (50.5%). The results showed that 74.7% of the studied population reported at least one local or systemic side effect. These side effects were more frequent among adenoviral-vector vaccinees (87.3%) than inactivated-virus vaccinees (60.6%) (sig. < 0.001). Injection site pain (40.3%), heat at the injection site (21.4%), and arm pain (16.3%) were the most common local side effects. These signs generally appeared in the first 12 h (73.3%) and generally lasted less than 24 h (32.8%). More interestingly, these signs differed from those that followed the administration of primer doses (48.5%) and were generally more severe (37%). The same observation was reported for systemic side effects, where the signs were especially most severe in the adenoviral-vaccinated group (49.4% vs. 20.8%; sig. = 0.001). These signs generally appeared within the first day (63.6%) and mostly disappeared before two days (50.8%), with fatigue (41.8%), fever (41.3%), and headache (30.1%) being the most common. Adenoviral-vector vaccinees (62.7%) were more likely to use medications to manage these side effects than were inactivated-virus vaccinees (45.7%) (sig. = 0.035) and paracetamol (48.5%) was the most used medication. Adenoviral-based vaccines were the types of vaccines that were most likely to cause side effects. In addition, being female increased the risk of developing side effects; regular medication was associated with local side effects among inactivated-virus vaccinees; and previous infection with COVID-19 was associated with systemic and local side effects among adenovirus-based vaccinees. These results support the short-term safety of booster vaccines, as has been reported for primer doses. Full article

Vaccines have been recognized as having a central role in controlling the COVID-19 pandemic; however, most vaccine development research is focused on IgG-induced antibodies. Here, we analyzed the generation of IgGs related to SARS-CoV-2 and the changes in B- and T-lymphocyte proportions following vaccination against COVID-19. We included samples from 69 volunteers inoculated with the Pfizer-BioNTech (BNT162b2), Astra Zeneca (AZD1222 Covishield), or Sputnik V (Gam-COVID-Vac) vaccines. IgGs related to SARS-CoV-2 increased after the first vaccine dose compared with the nonvaccinated group (Pfizer, p = 0.0001; Astra Zeneca, p < 0.0001; Sputnik V, p = 0.0089). The results of the flow cytometry analysis of B- and T-lymphocytes showed a higher proportion of effector-memory B-lymphocytes in both first and second doses when compared with the nonvaccinated subjects. FcRL4+ cells were increased in second-dose-vaccinated COVID-19(−) and recovered COVID-19(+) participants when compared with the nonvaccinated participants. COVID-19(−) participants showed a lower proportion of follicular helper T-lymphocytes (TFH) in the second dose when compared with the first-vaccine-dose and nonvaccinated subjects. In conclusion, after the first vaccine dose, immunization against SARS-CoV-2 induces IgG production, and this could be mediated by TFH and effector-memory B-lymphocytes. Our data can be used in the design of vaccine schedules to evaluate immuno-bridging from a cellular point of view. Full article

In this study involving a cohort of employees of the National Airline company in Lebanon, we assessed humoral immunity levels and the effectiveness of two COVID-19 vaccines, Gam-COVID-Vac versus BNT162b2, after two doses and after a homologous and heterologous BNT162b2 booster, in addition to the impact of hybrid immunity. Vaccine effectiveness (VE) was retrospectively determined against laboratory-confirmed SARS-CoV-2 infection during the periods of Delta and Omicron variants’ predominance, separately, and was calculated based on a case–control study design. The humoral immune response, measured by a SARS-CoV-2 anti-spike receptor-binding domain (RBD) IgG titer, was prospectively assessed after the aforementioned vaccination schemes at different time points. This study showed higher effectiveness of BNT162b2 after two doses (81%) compared to two doses of Gam-COVID-Vac (41.8%) against the Delta variant of SARS-CoV-2, which correlated with anti-spike antibody levels. Regarding the Omicron variant, protection against infection and antibody levels were severely compromised and the correlation between an anti-spike IgG titer and effectiveness was lost, unlike the situation during the Delta wave. Considering the booster vaccination schemes, a homologous BNT162b2 booster after a BNT162b2 primary vaccination induced a higher humoral immune response when compared to that induced by a heterologous BNT162b2 booster after a Gam-COVID-Vac primary vaccination. However, the VE of both booster regimens against the Omicron variant was almost equal (64% in the homologous regimen and 57% in heterologous regimen). Hybrid immunity evidenced a better humoral response and a greater and longer protection against Delta and Omicron infections compared to vaccination-induced immunity in COVID-19-naïve individuals. Finally, the findings show that VE waned with time during the same wave, highlighting the importance of reinforcing primary and booster COVID-19 vaccination mainly at the beginning of each wave during the surge of a new variant of concern. Full article