Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92–3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15–2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91–0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94–0.96), and multimorbidity (RR = 0.89, CI = 0.80–1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80–0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity. Full article

The Coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), continues to surge despite the widespread use of vaccination. In Thailand, more than 77% and 39% of the population received two doses and three doses of COVID-19 vaccines as of December 2022, respectively. In addition, during the Omicron predominant period in 2022, more than 70% of Thai individuals have been infected. To gain comprehensive insight into SARS-CoV-2 antibody dynamics following vaccination or following vaccination and infection (hybrid immunity), we performed a cross-sectional analysis of sera samples from individuals who received COVID-19 vaccination and/or have been infected with COVID-19 in Thailand between January 2021 and December 2022. A total of 4126 samples were collected. Humoral immunity was evaluated by quantifying the immunoglobulin (including IgG, IgM, and IgA isotypes) specific to the SARS-CoV-2 receptor-binding domain (RBD) or Ig anti-RBD. The results showed that individuals who received two-dose vaccination alone had lower levels of Ig anti-RBD, which rapidly waned over time. To restore the waning antibody, a third dose vaccination is recommended for uninfected individuals who have only received 2 doses. Full article

This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated individuals without prior SARS-CoV-2 infection, with an exponential increase observed in just six days. In those without a COVID-19 history, similar antibody production was reached 45 days after vaccination. Although total antibodies decline considerably in the first two months, the neutralizing antibodies and their inhibitory capacity (>96%) persist up to 6 months after the first dose. There was a tendency for higher total antibodies in women than men, but not at the inhibition capacity level. We suggest that the decline in total antibodies should not be considered as an indicator of loss of protective immunity because most antibodies decay two months after the second dose, but neutralizing antibodies remain constant for at least six months. Therefore, these latter antibodies could be better indicators for estimating the time-dependent vaccine efficacy. Full article

IgA plays a crucial role in early virus neutralization. To identify the IgA stimulation by COVID-19 vaccine, this study aimed to evaluate the level of anti-S1 IgA in the serum of participants immunized with different COVID-19 vaccination regimens. Sera from 567 eligible participants vaccinated with two, three, or four doses of different types of COVID-19 vaccine were recruited. Post-vaccine anti-S1 IgA responses significantly varied according to vaccine type and regimen. The finding showed that heterologous boosters, especially after priming with an inactivated vaccine, elicited higher IgA levels than homologous boosters. Vaccination with SV/SV/PF produced the highest IgA level among all the immunization regimens after either two, three, or four doses. The different routes and amounts of vaccine used for vaccination showed non-significant differences in IgA levels. After the third dose of immunization for 4 months, the level of IgA decreased significantly from the level found on day 28 in both SV/SV/AZ and SV/SV/PF groups. In conclusion, our study showed that heterologous booster regimens for COVID-19 elicited higher anti-S1 IgA levels in serum, especially after priming with inactivated vaccine. The presented anti-S1 IgA may have advantages in preventing SARS-CoV-2 infection and severe disease. Full article

(1) Background: Children and young adults with cancer are poorly represented in COVID-19 vaccination studies, and long-term protection conferred by vaccination is not known. (2) Objectives: 1. To determine the adverse effects associated with BNT162B2 vaccination in children and young adults with cancer. 2. To assess its efficacy in stimulating immunological response and in preventing severe COVID-19 disease. (3) Methods: Retrospective single-center study evaluating patients aged 8 to 22 years, with cancer, who underwent vaccination from January 2021 to June 2022. ELISA serologies and serum neutralization were collected monthly from the first injection. Serologies below 26 were considered negative, while those above 264 BAU/mL were considered positive and indicative of protection. Antibodies titers were considered positive above 20. Data on adverse events and infections were collected. (4) Results: 38 patients were included (M/F = 1.7, median age 16 years), of whom 63% had a localized tumor and 76% were undergoing treatment at the time of the first vaccination. Two or three vaccine injections were administered in 90% of patients. Adverse events were mainly systemic and not severe, except for seven grade 3 toxicities. Four cancer-related deaths were reported. Median serology was negative the month following the first vaccination and became protective during the third month. At 3 and 12 months, median serology was 1778 and 6437 BAU/mL, respectively. Serum neutralization was positive in 97% of the patients. COVID-19 infection occurred despite vaccination in 18%; all were mild forms. (5) Conclusions: In children and young adults with cancer, vaccination was well tolerated and conferred effective serum neutralization. COVID-19 infections were mild, and vaccine seroconversion persisted after 12 months in most patients. The value of additional vaccination should be further established. Full article

The early availability of effective vaccines against SARS-CoV-2, the aetiologic cause of COVID-19, has been at the cornerstone of the global recovery from the pandemic. This study aimed to assess the antispike RBD IgG antibody titres and neutralisation potential of COVID-19 convalescent plasma and the sera of Moldovan adults vaccinated with the Sinopharm BBIBP-CorV vaccine. An IgG ELISA with recombinant SARS-CoV-2 spike RBD and two pseudovirus-based neutralisation assays have been developed to evaluate neutralising antibodies against SARS-CoV-2 in biosafety level 2 containment facilities. A significant moderate correlation was observed between IgG titres and the overall neutralising levels for each neutralisation assay (ρ = 0.64, p < 0.001; ρ = 0.52, p < 0.001). A separate analysis of convalescent and vaccinated individuals showed a higher correlation of neutralising and IgG titres in convalescent individuals (ρ = 0.68, p < 0.001, ρ = 0.45, p < 0.001) compared with vaccinated individuals (ρ = 0.58, p < 0.001; ρ = 0.53, p < 0.001). It can be concluded that individuals who recovered from infection developed higher levels of antispike RBD IgG antibodies. In comparison, the Sinopharm-vaccinated individuals produced higher levels of neutralising antibodies than convalescent plasma. Full article

Background: Maternal vaccination is safe and provides protection against COVID-19 in mothers and neonates, and it is necessary to evaluate its effect on the induction of immune responses through the levels of neutralizing antibodies present in maternal and neonatal blood. Methods: An observational study with transversal analysis was carried out. Included in the research were neonates (<1 month) whose mothers had been immunized whilst pregnant with at least one dose of the vaccine BNT16b and had not shown any symptoms of COVID-19. The blood of the mothers and newborns was collected during the Guthrie test and sent to the laboratory for the detection of neutralizing antibodies against SARS-CoV-2. Results: A total of 162 pairs of mothers and neonates were analyzed with an average age of 26.3 ± 5.97 years and 13.4 ± 6.90 days, respectively. All samples collected present neutralizing antibodies with an average percentage of 91% in the mothers and 92% in the neonates. The most satisfactory immune response was observed in neonates and mothers vaccinated during the second trimester of gestation. Conclusions: The vaccination of expectant mothers with the immunizer BNT162b2 has promoted a robust immunological response in both the mothers and the neonates. Full article

Immunogenicity after SARS-CoV-2 vaccination is known to be impaired in liver transplant (LT) recipients, but the results after the application of a third dose show significant improvement in seroconversion rates. In the general population, the antibody response wanes over the course of time after two doses of the vaccination, but seems to be more robust after the application of three doses. Still, the durability of the antibody response in LT recipients who receive a third dose of SARS-CoV-2 vaccination has not been analyzed yet. We therefore assessed antibody responses in a total of 300 LT recipients and observed antibody titers for six months each after patients had received the second and the third doses of the vaccination, explicitly excluding all patients who had suffered from SARS-CoV-2 infection. The initial antibody response was compared to a control group of 122 healthcare workers. After the application of two doses of the vaccination, 74% of LT recipients (158 out of 213) developed antibodies against SARS-CoV-2; this result depended significantly on whether the patients were taking the medication mycophenolate mofetil, and on the age of the patients. Antibody titers declined significantly within six months from 407 BAU/mL (IQR: 0–1865) to 105 BAU/mL (IQR: 0–145) (p ≤ 0.001), but increased after the application of the third vaccine dose in 92% of patients (105 out of 114), showing an antibody response (p ≤ 0.001). After a further six-month period, despite showing a decline from 2055 BAU/mL (IQR: 500 to >2080) to 1805 BAU/mL (IQR: 517 to >2080), the waning of antibody titers was not significant (p = 0.706), and antibody durability appeared to be more robust than that after the second dose. In conclusion, our study confirms the high efficacy of the application of a third dose of SARS-CoV-2 vaccination in LT recipients, and a reasonably sustained humoral response with superior durability in comparison to antibody kinetics after the application of the second dose of the vaccination. Full article

The changes in the severe acute respiratory syndrome coronavirus 2 and the tapering of immunity after vaccination have propelled the need for a booster dose vaccine. We aim to evaluate B and T cell immunogenicity and reactogenicity of mRNA-1273 COVID-19 vaccine (100 µg) as a third booster dose after receiving either two doses of inactivated COVID-19 vaccine (CoronaVac) or two doses of viral vector vaccine (AZD1222) in adults not previously infected with COVID-19. The anti-receptor-binding-domain IgG (anti-RBD IgG), surrogate virus neutralization test (sVNT) against the Delta variant, and Interferon-Gamma (IFN-γ) level were measured at baseline, day (D)14 and D90 after vaccination. In D14 and D90, the geometric means of sVNT were significantly increased to 99.4% and 94.5% inhibition in CoronaVac, respectively, whereas AZD1222 showed inhibition of 99.1% and 93%, respectively. Anti-RBD IgG levels were 61,249 to 9235 AU/mL in CoronaVac and 38,777 to 5877 AU/mL in AZD1222 after D14 and D90 vaccination. Increasing median frequencies of S1-specific T cell response by IFN-γ concentration were also elevated in D14 and were not significantly different between CoronaVac (107.8–2035.4 mIU/mL) and AZD1222 (282.5–2001.2 mIU/mL). This study provides evidence for the high immunogenicity of the mRNA-1273 booster after two doses of CoronaVac or AZD1222 in the Thai population. Full article

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed. Full article

Objectives. Since the outbreak of SARS-CoV-2 in late 2019, nearly 12.2 billion doses of the COVID-19 vaccine have been administered worldwide; however, the humoral immune responses induced by different types of vaccines are yet to be fully validated. Methods. We analyzed antibody levels in 100 serum samples after vaccination with different types of COVID-19 vaccines and their reactivity against the RBD antigen of Delta and Omicron variants using a bead-based microarray. Results. Elevated levels of anti-wild-type (WT)-RBD IgG and anti-WT-NP IgG were detected in participants who received two doses of the inactivated vaccines (CoronaVac or BBIBP-CorV) and three doses of the recombinant spike protein vaccine (ZF2001), indicating that antibody responses to SARS-CoV-2 were generated regardless of the vaccine administered. We found highly correlated levels of serum anti-RBD IgG and anti-NP IgG (r = 0.432, p < 0.001). We observed that the antibodies produced in vivo after COVID-19 vaccination still reacted with variants of SARS-CoV-2 (p < 0.0001). Conclusions. Our results show that high levels of specific antibodies can be produced after completion of COVID-19 vaccination (two doses of the inactivated vaccines or three doses of ZF2001), with some degree of cross-reactivity to the RBD antigen of Delta and Omicron variants, and provide an accessible and practical experimental method for post-vaccination antibody detection. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019. Anti-SARS-CoV-2 spike (S) and neutralizing antibodies (Abs) are measured to evaluate the efficacy of vaccines. Human leukocyte antigen (HLA) may be associated with vaccine efficacy. Here, we investigated the association of HLA polymorphisms with the production of anti-SARS-CoV-2 S or neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Genotyping of DRB1 and DQB1 was conducted in 87 Japanese RA patients vaccinated with BNT162b2. Associations of allele or haplotype carrier frequencies with anti-SARS-CoV-2 S or neutralizing Abs were examined. DRB1*12:01 was significantly positively associated with the production of S Ab (p = 0.0225, odds ratio [OR] 6.08, 95% confidence interval [CI] 1.32–28.03). The DQB1*03:01 allele carrier frequency tended to be higher in high responders of S Ab. Allele carrier frequencies of DRB1*15:01 (p = 0.0102, OR 9.26, 95% CI 1.65–52.01) and DQB1*06:02 (p = 0.0373, OR 7.00, 95% CI 1.18–41.36) were higher in responders of neutralizing Ab. Haplotype and two-locus analyses of DRB1 and DQB1 suggested that DRB1 alleles were the primary drivers of these associations. Logistic regression analysis showed associations of these alleles independent of clinical characteristics. Independent associations were found between HLA alleles and anti-SARS-CoV-2 Ab production by vaccinated RA patients. Full article

Numerous vaccines have been generated to decrease the morbidity and mortality of COVID-19. This study aims to evaluate the immunogenicity of the heterologous boosts by BioNTech against homologous boosts by CoronaVac at three-month intervals in two health care worker (HCW) cohorts, with or without prior COVID-19, for one year post-vaccination. This is a prospective cohort study in which the humoral responses of 386 HCWs were followed-up longitudinally in six main groups according to their previous COVID-19 exposure and vaccination status. Anti-SARS-CoV-2 spike-RBD total antibody levels were measured and SARS-CoV-2 neutralization antibody (NAbs) responses against the ancestral Wuhan and the Omicron variant were evaluated comparatively using international standard serum for Wuhan and Omicron, as well as with the aid of a conversion tool. The anti-SARS-CoV-2 spike-RBD total Ab and Nab difference between with and without prior COVID-19, three months after two-dose primary vaccination with CoronaVac, was statistically significant (p = 0.001). In the subsequent follow-ups, this difference was not observed between the groups. Those previously infected (PI) and non-previously infected (NPI) groups receiving BioNTech as the third dose had higher anti-SARS-CoV-2 spike total Ab levels (14.2-fold and 17.4-fold, respectively, p = 0.001) and Nab responses (against Wuhan and Omicron) than those receiving CoronaVac. Ab responses after booster vaccination decreased significantly in all groups at the ninth-month follow-up (p < 0.05); however, Abs were still higher in all booster received groups than that in the primary vaccination. Abs were above the protective level at the twelfth-month measurement in the entire of the second BioNTech received group as the fourth dose of vaccination. In the one-year follow-up period, the increased incidence of COVID-19 in the groups vaccinated with two or three doses of CoronaVac compared with the groups vaccinated with BioNTech as a booster suggested that continuing the heterologous CoronaVac/BioNTech vaccination, revised according to current SARS-CoV-2 variants and with at least a six-month interval booster would be an effective and safe strategy for protection against COVID-19, particularly in health care workers. Full article

Messenger RNA (mRNA) vaccination was developed to mitigate the coronavirus disease 2019 pandemic. However, data on antibody kinetics and factors influencing these vaccines’ immunogenicity are limited. We conducted a prospective study on healthy young adults who received two doses of the mRNA-1273 vaccine at 28-day intervals. After each dose, adverse events were prospectively evaluated, and blood samples were collected. The correlation between humoral immune response and reactogenicity after vaccination was determined. In 177 participants (19–55 years), the geometric mean titers of anti-S IgG antibody were 178.07 and 4409.61 U/mL, while those of 50% neutralizing titers were 479.95 and 2851.67 U/mL four weeks after the first and second vaccine doses, respectively. Anti-S IgG antibody titers were not associated with local reactogenicity but were higher in participants who experienced systemic adverse events (headache and muscle pain). Antipyretic use was an independent predictive factor of a robust anti-SARS-CoV-2 antibody response after receiving both vaccine doses. Systemic reactogenicity after the first dose influenced antibody response after the second dose. In conclusion, mRNA-1273 induced a robust antibody response in healthy young adults. Antipyretic use did not decrease the anti-SARS-CoV-2 antibody response after mRNA-1273 vaccination. 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

Data on immunogenicity of adenovirus-vectored vaccine in chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, we aimed to determine the humoral and cellular immune responses after homologous ChAdOx-1 vaccination in subjects with COPD. COPD subjects and age- and sex-matched healthy elderly receiving ChAdOx-1 homologous vaccination were included. The levels of neutralizing antibodies (NAb) and specific CD4 and CD8 T-cell responses against SARS-CoV-2 wild-type (WT) and variants of concern (VOCs: Alpha, Beta, Delta, and Omicron) were measured. Eight COPD patients were matched with eight control participants. After vaccination for 4 and 12 weeks, % inhibition of NAb against Alpha, Beta, and Delta in both groups were comparable and significantly higher than baseline. The percentage inhibition of NAb at the 12th week was significantly dropped from the 4th week in each group. The NAb against the Omicron variant, however, were much lower than Alpha, Beta, Delta variants. The increasing trend in the number of CD4 T-cells producing TNF-α, IFN-γ, IL-10, and FasL upon stimulation with spike peptides of WT and VOCs was observed in COPD patients compared to the healthy group. These responses were not observed in CD8 T-cells. Homologous ChAdOx-1 vaccination could induce comparable NAb against the SARS-CoV-2 WT, Alpha, Beta, Delta, and Omicron variants between COPD and healthy elderly. The CD4 T-cell responses did not differ between COPD patients and healthy control. Full article

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have reduced susceptibility to neutralization by vaccines. In response to the constantly updated variants, a global vaccine booster vaccination program has been launched. In this study, we detected neutralizing antibody levels against wild-type (WT), Delta (B1.617.2), and Omicron BA.1 viruses in serum after each dose of CoronaVac vaccination. We found that booster vaccination significantly increased the levels of neutralizing antibodies against WT, Delta, and Omicron BA.1. Compared with only one vaccination, neutralizing antibody levels increased by 19.2–21.6-fold after a booster vaccination, whilst two vaccinations only produced a 1.5–3.4-fold increase. Our results support the conclusion that the CoronaVac vaccine booster can increase neutralizing antibody levels and cross-reactivity and enhance the body’s ability to effectively resist the infection of new coronavirus variants, emphasizing the need for booster vaccination. Full article

We evaluated the immune response against the Omicron variant after mRNA-based COVID-19 booster vaccination in medical students. We prospectively enrolled medical students who received two primary doses of the mRNA-1273 vaccine. The neutralizing response and the SARS-CoV-2-specific T-cell response was evaluated. A total of 56 serum samples were obtained before booster vaccination. Nineteen students (33.9%) developed COVID-19 two months after booster vaccination. Of 56 students, 35 students (12 infected and 23 uninfected) were available for blood sampling four months after booster vaccination. In comparison with uninfected students, infected students showed a significantly higher level of SARS-CoV-2-specific IgG (5.23 AU/mL vs. 5.12 AU/mL, p < 0.001) and rate of neutralizing response (96.22% vs. 27.18%, p < 0.001) four months after booster vaccination. There was no significant difference in the SARS-CoV-2-specific T-cell response. Among 23 infection-naive students, the neutralizing response was significantly higher in those who received the mRNA-1273 booster than in those who received the BNT162b2 booster (69.07% vs. 26.43%, p = 0.02). In our study, booster vaccination with mRNA-1273 instead of BNT162b2 was significantly associated with a higher neutralizing response. Full article

We conducted a prospective study to evaluate immune responses to SARS-CoV-2 in oncology workers in which we collected blood and clinical data every 6 months. Spike-specific CD4⁺ T-cells and immunoglobulin G responses were measured using interferon-gamma enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay, respectively. Sixty (81%) vaccinated and 14 (19%) unvaccinated individuals were enrolled. CD4⁺ T-cell responses of those individuals currently naturally infected were comparable to those who were 6 months from receiving their last dose of the vaccine; both responses were significantly higher than among those who were unvaccinated. Unvaccinated participants who became vaccinated while in the study showed a significant increase in both types of spike-specific immune responses. Previously vaccinated individuals who received a third dose (booster) showed a similar response to the spike protein. However, this response decreases as soon as 3 months but does not dip below the established response following two doses. Response to variants of concern B.1.617.2 (Delta) and B.1.1.529 (Omicron) also increased, with the Omicron variant having a significantly lower response when compared to Delta and the wild type. We conclude that antibody and T-cell responses increase in oncology workers after serial vaccination but can wane over time Full article

In vaccine clinical trials, both binding antibody (bAb) levels and neutralization antibody (nAb) titers have been shown to be correlates of SARS-CoV-2 vaccine efficacy. We report a strong correlation bAb and nAb responses against the SARS-CoV-2 Omicron (BA.1) variant in infection-naïve and previously infected (convalescent) individuals after one and two doses of BNT162b2 vaccination. The vaccine-induced bAb levels against Omicron were significantly lower compared to previous variants of concern in both infection-naive and convalescent individuals, with the convalescent individuals showing significantly higher bAb compared to the naïve individuals at all timepoints. The finding that bAb highly correlated with nAb provides evidence for utilizing binding antibody assays as a surrogate for neutralizing antibody assays. Our data also revealed that after full vaccination, a higher percentage of individuals had undetectable Omicron nAb (58.6% in naive individuals, 7.4% in convalescent individuals) compared to the percentage of individuals who had negative Omicron bAb (0% in naive individuals, 0% in convalescent individuals). The discordance between bAb and nAb activities and the high degree of immune escape by Omicron may explain the high frequency of Omicron infections after vaccination. Full article

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1–2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT₅₀ ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse. Full article

This study aimed to investigate the efficacy of different COVID-19 booster vaccines by measuring the serum antibody titer. SARS-CoV-2 anti-nucleocapsid protein antibody (N-Ab), anti-spike protein antibody (S-Ab), and neutralizing antibody (Neut.Ab) were measured before and 4–6 weeks after booster vaccinations in healthcare personnel with a previous vaccination within 3–6 months. Personnel who previously received two doses of ChAdOx1 vaccine or two doses of BNT162b2 vaccine received the BNT162b2 vaccine (AAP and PPP groups, respectively). Personnel who previously received two doses of mRNA-1273 received the same vaccine as a booster dose (MMM group). Of the 917 participants, the AAP, MMM, and PPP groups comprised 837 (91.3%), 27 (2.9%), and 53 (5.8%) participants, respectively. The pre-booster S-Ab and Neut.Ab titer were significantly lower in the AAP group. After the booster vaccination, all participants were positive for S-Ab and Neut.Ab; furthermore, the S-Ab and Neut.Ab titer significantly increased in all three groups, although the post-booster S-Ab was lower in the AAP group than in the other groups. The post-booster Neut.Ab titer showed no significant difference among the groups. Our study’s results suggest that booster vaccination, after two prior vaccinations, shows a significant effect regardless of the type of vaccine administered. Full article

Most of the current SARS-CoV-2 vaccines are based on parenteral immunization targeting the S protein. Although protective, such vaccines could be optimized by inducing effective immune responses (neutralizing IgA responses) at the mucosal surfaces, allowing them to block the virus at the earliest stage of the infectious cycle. Herein a recombinant chimeric antigen called LTB-RBD is described, which comprises the B subunit of the heat-labile enterotoxin from E. coli and a segment of the RBD from SARS-CoV-2 (aa 439-504, carrying B and T cell epitopes) from the Wuhan sequence and the variant of concern (VOC)—delta. Since LTB is a mucosal adjuvant, targeting the GM1 receptor at the surface and facilitating antigen translocation to the submucosa, this candidate will help in designing mucosal vaccines (i.e., oral or intranasal formulations). LTB-RBD was produced in E. coli and purified to homogeneity by IMAC and IMAC-anionic exchange chromatography. The yields in terms of pure LTB-RBD were 1.2 mg per liter of culture for the Wuhan sequence and 3.5 mg per liter for the delta variant. The E. coli-made LTB-RBD induced seric IgG responses and IgA responses in the mouth and feces of mice when subcutaneously administered and intestinal and mouth IgA responses when administered nasally. The expression and purification protocols developed for LTB-RBD constitute a robust system to produce vaccine candidates against SARS-CoV-2 and its variants, offering a low-cost production system with no tags and with ease of adaptation to new variants. The E. coli-made LTB-RBD will be the basis for developing mucosal vaccine candidates capable of inducing sterilizing immunity against SARS-CoV-2. Full article

Background: There is debate on the necessity of booster doses of COVID-19 vaccination, especially in countries with limited resources. Methods: This cross-sectional study was conducted in a referral laboratory in Tehran, Iran. The level of COVID-19 antibodies was measured and compared between individuals regarding the number of COVID-19 vaccine shots. Results: In this study, 176 individuals with a mean age of 36.3 (±11.7) years participated. A total of 112 individuals received two doses of the COVID-19 vaccine, and 64 individuals received three doses. Level of all antibodies was higher in those who received three doses than in those who received two doses of the COVID-19 vaccine. Considering the SARS-CoV-2 Spike IgG, the difference was not statistically significant but for the SARS-CoV-2 RBD IgG and SARS-CoV-2 NAB the difference was statistically significant. Regarding to the background variables, receiving influenza vaccine in the past year, history of autoimmune diseases and past medical history of chicken pox showed a significant association with the number of vaccine doses received. Their effects on the outcome variables assessed with multivariate logistic regression analysis. Conclusion: The results of our study show that a booster dose of the COVID-19 vaccine enhances the antibody response. Full article

This study aimed to determine the anti-S (receptor binding protein) RBD IgG antibody titers formed against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the neutralizing antibody inhibition percentages (nAb IH%) in blood samples taken after two doses of inactive or mRNA-based vaccine and a booster dose. Volunteers with two doses of inactivated CoronaVac (heterologous group; n = 75) and BioNTech (BNT)162b2 mRNA vaccine (homologous group; n = 75) were included in this study. All participants preferred the BNT162b2 vaccine as a booster dose. First, peripheral blood samples were taken 3 months after the second vaccine dose. Second, peripheral blood samples were taken 1 month after the booster dose. Anti-S-RBD IgG titers were determined by CMIA (SARS-CoV-2 IgG II Quant). Neutralizing antibodies were detected by a surrogate neutralization assay (SARS-CoV-2 NeutraLISA, Euroimmun, Lübeck, Germany). The median age of the volunteers was 40 (IQR 29–47) years old. After the heterologous booster dose, anti-S-RBD IgG levels and neutralizing antibodies increased approximately 50-fold and 9-fold, respectively. Anti-S-RBD IgG titers increased by 9 and 57 times, respectively, while nAb IH% increased by 1.5 and 16 times, respectively, among those with heterologous reminder doses and those with and without a prior history of coronavirus disease (COVID-19). This study showed that after the administration of a heterologous booster dose with BNT162b2 to those whose primary vaccination was with inactivated CoronaVac, the binding and neutralizing antibody levels were similar to those who received a homologous BNT162b2 booster dose. It was observed that the administration of heterologous and homologous booster doses resulted in the development of similar levels of neutralizing antibodies, independently from a prior history of COVID-19. Full article

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2–10.4), shorter interval between vaccine doses (aOR 1.6, 1.2–2.1, 6–10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4–7.0), immunodeficiency (aOR 6.5, 2.5–16.6) and immunosuppressant use (aOR 3.7, 2.4–5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0–0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5–0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8–44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2–16.9, for 9–16 weeks vs. 2–4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7–16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October–December vs. April–June (47.7% lower, 11.4–69.1), older age (3.3% lower per 10-year increase in age, 2.1–4.6), and hypertension (4.1% lower, 1.1–6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0–31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9–21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2–5.7, for BMI 25–30 vs. <25 kg/m²) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1–116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable. Full article

This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5–7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark. Full article

The COVID-19 wave is being recently propelled by BA.2 and, particularly, BA.5 lineages, showing clear transmission advantages over the previously circulating strains. In this study, neutralizing antibody responses against SARS-CoV-2 Wild-Type, BA.2 and BA.5 Omicron sublineages were evaluated among vaccinees, uninfected or infected with Omicron BA.1 strain, 8 months after the third dose of SARS-CoV-2 vaccine. The aim of this study was to compare the cross-protective humoral response to the currently circulating variant strains induced by vaccination, followed by Omicron infection in some subjects. Results showed a low antibody titer against all three variants in uninfected vaccinated subjects. On the other hand, vaccinated subjects, infected with BA.1 variant after receiving the third dose (about 40 days later), showed a strong response against both BA.2 and BA.5 strains, albeit with lower titers. This reinforces the concept that vaccination is fundamental to induce an adequate and protective immune response against SARS-CoV-2, but needs to be updated, in order to also widen the range of action towards emerging variants, phylogenetically distant from the Wuhan strain, against which the current formulation is targeted. Full article

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020–August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (β = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings. Full article

The aim of our study was to determine whether local and systemic reactions following SARS-CoV-2 vaccination are predictive of immunogenicity in patients undergoing hemodialysis. We used an established questionnaire to survey 206 hemodialysis patients without prior SARS-CoV-2 infection regarding solicited local (pain, redness, and swelling) and systemic reactions (fatigue, headache, muscle and joint pain, nausea or vomiting, abdominal pain, diarrhea, and fever) within 7 days after receiving 1 dose of the ChAdOx1 nCoV-19 vaccine for SARS-CoV-2. The primary outcome was seroconversion of anti-SARS-CoV-2 IgG (≥50 AU/mL) at 28 days after vaccination. Local and systemic reactions were reported by 80 (38.8%) and 119 (57.8%) patients, respectively. A total of 138 (67.0%) patients developed an antibody response. Responders were younger, had a lower prevalence of coronary artery disease and use of immunosuppressants, and had a higher body mass index and lymphocyte count. In addition, a greater percentage of responders than non-responders reported reactogenicity. In multivariate logistic regression analyses, fever (OR 2.70 [95% CI 1.12–6.50]) and total symptom score (OR 1.33 [95% CI, 1.05–1.68], per one increase) remained strongly associated with a greater humoral response. In conclusion, higher reactogenicity may identify hemodialysis patients who are more responsive to SARS-CoV-2 vaccination. Full article

With the development of SARS-CoV-2 vaccines, many authors started evaluating the immunization efficacy of the available vaccines mainly through sero-positivity tests or by a quantitative assessment of the IgG against the spike protein of SARS-CoV-2 virus in vaccinated subjects. In this work, we compared the titers resulting from vaccination and tried to understand the potential factors affecting the immune response to the available SARS-CoV-2 vaccines. This study was conducted on 670 volunteers employed at the University of Pisa and undergoing a health surveillance program at the University Hospital of Pisa. For each participant, 10 mL of blood, information about contacts with confirmed cases of COVID-19, age, sex, SARS-CoV-2 vaccination status, previous SARS-CoV-2 infection and symptoms, type of vaccine and the date of administration were collected. In the multivariate analysis, the type of vaccine, the presence of symptoms in SARS-CoV-2 positive individuals, and the distance from the second dose significantly affected the antibody titer; the combined vaccination resulted in a faster decay over time compared with the other types of vaccination. No significant differences were observed between Spikevax and Comirnaty (p > 0.05), while the antibody levels remain more stable in subjects undergoing Vaxzevria vaccination (p < 0.01) compared with mRNA-based ones. Full article

Recombinant trimeric SARS-CoV-2 Spike protein with PIKA (polyI:C) adjuvant induces potent and durable neutralizing antibodies that protect against multiple SARS-CoV-2 variants. The immunoglobulin subclasses of viral-specific antibodies remain unknown, as do their glycosylation status on Fc regions. In this study, we analyzed immunoglobulins adsorbed by plate-bound recombinant trimeric SARS-CoV-2 Spike protein from serum of Cynomolgus monkey immunized by recombinant trimeric SARS-CoV-2 Spike protein with PIKA (polyI:C) adjuvant. The results showed that IgG1 was the dominant IgG subclass as revealed by ion mobility mass spectrometry. The average percentage of Spike protein-specific IgG1 increased to 88.3% as compared to pre-immunization. Core fucosylation for Fc glycopeptide of Spike protein-specific IgG1 was found to be higher than 98%. These results indicate that a unique Th1-biased, IgG1-dominant antibody response was responsible for the effectiveness of PIKA (polyI:C) adjuvant. Vaccine-induced core-fucosylation of IgG1 Fc region may reduce incidence of severe COVID-19 disease associated with overstimulation of FCGR3A by afucosylated IgG1. Full article

Serum sickness-like reaction from serum sickness is critical. Serum sickness-like reaction has comparable symptoms to serum sickness, but their underlying pathophysiology is distinct. This delayed hypersensitivity response was first characterized as a drug-induced reaction and is uncommon in adults; it is more common in children. COVID-19 vaccinations are now being routinely given in the COVID-19 period, and adverse reactions to immunization have been recorded. We present a case of COVID-19 vaccination-induced serum sickness-like reaction which developed after receiving the first dose of AstraZeneca COVID-19 vaccine. Full article