Project description:Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg mRNA) and mRNA-1273 (100 μg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 μg mRNA) than BNT162b2 (30 μg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.
Project description:SARS-CoV-2 proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. 11 of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day one after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of IgG and IgA.
Project description:Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, obtained the Emergency Use Listing by WHO for preventing COVID-19. However, little is known about the difference in antibody responses induced by these two mRNA vaccines in naïve and previously infected (PI) individuals. We investigated the levels of anti-S-RBD (total, IgG and IgA) levels in naïve and PI individuals, 1-13 (median = 6) weeks following the second dose of either vaccine. Results in the naïve-vaccinated group, the mRNA-1273 vaccine induced significantly higher levels of anti-S-RBD total antibodies (3.5-fold; P < 0.001), IgG (2-fold, P < 0.01) and IgA (2.1-fold, P < 0.001) as compared with the BNT162b2 vaccine. In addition, both vaccines produced significantly higher anti-S-RBD total antibody levels in the PI-group compared with naïve-vaccinated group. The PI group elicited a higher level of anti-S-RBD IgG than the naïve-BNT162b2 (P = 0.05), but not more than the naïve-mRNA-1273 (P = 0.9) group. Interestingly, the PI vaccinated group elicited a comparable level of IgA ratio to the naïve-mRNA-1273 group but significantly higher than the naïve-BNT162b2 group (1.6-fold, P < 0.001). Our results showed that the PI-vaccinated group produces a higher level of antibodies than the naïve vaccinated group, particularly for those vaccinated with BNT162b2.
Project description:ObjectivesThere are limited comparative immunologic durability data post COVID-19 vaccinations.MethodsApproximately 8.4 months after primary COVID-19 vaccination, 647 healthcare workers completed surveys about COVID-19 vaccinations/infections and blood draws. The groups included participants vaccinated with mRNA-1273 (n = 387), BNT162b2 (n = 212), or Ad26.COV2.S (n = 10) vaccines; unvaccinated participants (n = 10); and participants who received a booster dose (n = 28). The primary outcome was immunoglobin anti-spike titer. Secondary/tertiary outcomes included neutralizing antibodies (enzyme-linked immunosorbent assay-based pseudoneutralization) and vaccine effectiveness (VE). Antibody levels were compared using analysis of variance and linear regression.ResultsMean age was 49.7 and 75.3% of the participants were female. Baseline variables were balanced except for immunosuppression, previous COVID-19 infection, and post-primary vaccination time. Unadjusted median (interquartile range [IQR]) anti-spike titers (AU/ml) were 1539.5 (876.7-2626.7) for mRNA-1273, 751.2 (422.0-1381.5) for BNT162b2, 451.6 (103.0-2396.7) for Ad26.COV2.S, 113.4 (3.7-194.0) for unvaccinated participants, and 31898.8 (21347.1-45820.1) for participants administered with booster dose (mRNA-1273 vs BNT162b2, P <.001; mRNA-1273, BNT162b2, or boosted vs unvaccinated, P <.006; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs boosted, P <.001). Unadjusted median (IQR) pseudoneutralization was as follows: 90.9% (80.1-95.0) for mRNA-1273, 77.2% (59.1-89.9) for BNT162b2, 57.9% (36.6-95.8) for Ad26.COV2.S, 40.1% (21.7-60.6) for unvaccinated, and 96.4% (96.1-96.6) for participants administered with booster dose (mRNA-1273 vs BNT162b2, P <.001; mRNA-1273, BNT162b2, or boosted vs unvaccinated, P <.028; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs boosted, P <.001). VE was 87-89% for participants administered mRNA-1273 vaccine, BNT162b2 vaccine, and booster dose, and 33% for Ad26.COV2.S (none significantly different).ConclusionAntibody responses 8.4 months after primary vaccination were significantly higher with mRNA-1273 than those observed with BNT162b2.
Project description:Coronavirus disease 2019 (COVID-19) vaccination in immunocompromised, especially transplant recipients, may induce a weaker immune response. But there are limited data on the immune response after COVID-19 vaccination in liver transplant (LT) recipients, especially on the comparison of Ab responses after different vaccine platforms between mRNA and adenoviral vector vaccines. Thus, we conducted a prospective study on LT recipients who received two doses of the ChAdOx1 nCoV-19 (ChAdOx1), mRNA-1273, or BNT162b2 vaccines compared with healthy healthcare workers (HCWs). SARS-CoV-2 S1-specific IgG Ab titers were measured using ELISA. Overall, 89 LT recipients (ChAdOx1, n=16 [18%]) or mRNA vaccines (mRNA-1273 vaccine, n=23 [26%]; BNT162b2 vaccine, n=50 [56%]) received 3 different vaccines. Of them, 16 (18%) had a positive Ab response after one dose of COVID-19 vaccine and 62 (73%) after 2 doses. However, the median Ab titer after two doses of mRNA vaccines was significantly higher (44.6 IU/ml) than after two doses of ChAdOx1 (19.2 IU/ml, p=0.04). The longer time interval from transplantation was significantly associated with high Ab titers after two doses of vaccine (p=0.003). However, mycophenolic acid use was not associated with Ab titers (p=0.53). In conclusion, about 3-quarters of LT recipients had a positive Ab response after 2 doses of vaccine, and the mRNA vaccines induced higher Ab responses than the ChAdOx1 vaccine.
Project description:According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.
Project description:Severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized.MethodsWe included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine.ResultsPositive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman's rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded.ConclusionsTwo-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.