DURABILITY OF HUMORAL AND CELL-MEDIATED IMMUNE RESPONSE AFTER SARS-CoV-2 mRNA VACCINE ADMINISTRATION.

Vaccination against the SARS-Cov-2 virus is an effective way to protect against the disease and the severe course of COVID-19. Forty-nine fully vaccinated with mRNA vaccines (BNT162b2 or mRNA-1273) SARS-CoV-2 infection-naïve volunteers aged 33-89 were enrolled in the study. Evaluation of the cellular and humoral immune response was performed within 1 to 3 months (T1) and 6-9 months (T2) after the second injection, and within 2-3 months (T3) after a booster dose. Additionally, a comparative analysis of the specific immune status was made between two age groups - below 60 (n=22) and over 60 (n=27) years. SARS-CoV-2-specific T-cell response was evaluated by IFN-γ-producing spot forming cells (SFCs) using a standardized ELISPOT assay. Virus neutralizing antibodies (VNA) against SARS-CoV-2 were measured by a blocking ELISA test and spike protein specific IgG (S-IgG) and IgA (S-IgA) antibodies - by semi-quantitative ELISA. IFN-γ-producing SFCs, S-IgG, S-IgA and VNA significantly decreased 6-9 months after the second dose. After the third injection S-IgG and S-IgA markedly increased compared to T2 and reached the levels at T1. Of note, the highest values of VNA were observed at T3. No differences in the tested immune parameters were found between the two age groups. Data obtained showed that for a long period - 6-9 months after a full course of immunization with mRNA vaccine, immune reactivity is present, but both cellular and humoral immune responses gradually decrease. The administration of a third dose mainly restores the specific humoral immune response against the SARS-CoV-2 virus. This article is protected by copyright. All rights reserved.

Assessment of humoral immune response to two mRNA SARS-CoV-2 vaccines (Moderna and Pfizer) in healthcare workers fully vaccinated with and without a history of previous infection.

AIMS: Presence of anti-S1 region of SARS-CoV-2 spike protein was analysed, at two and eight months, in 477 immunocompetent healthcare workers in Zaragoza, Spain, vaccinated with mRNA-1273 (Moderna) or BNT162b2 (Pfizer). METHODS AND RESULTS: Antibody analysis was performed with Alinity i System (Abbott). At 2 months, 100% of vaccinated had anti-S1 IgG (mean = 13,285 AU ml-1 ). This value was significantly higher with Moderna (18,192 AU ml-1 ) than with Pfizer (10,441 AU ml-1 ). The mean value of anti-S1 IgG after vaccination was significantly higher in patients with than without previous infection (18,539 vs. 7919 AU ml-1 ); in both groups was significantly higher with Moderna than with Pfizer (21,881 vs. 15,733 AU ml-1 and 11,949 vs. 6387 AU ml-1 ), respectively. At 8 months, 100% of patients were IgG positive, with higher levels with Moderna than with Pfizer. Nevertheless, in ensemble of cases, a mean decrease of antibody levels of 11,025 AU ml-1 was observed. CONCLUSION: At 2 and 8 months after vaccination, IgG response persists with both vaccines but with important decrease which suggests the need for revaccination. SIGNIFICANCE AND IMPACT OF STUDY: The study contributes to know the immune status after vaccination with two of more used anti-SARS-CoV-2 vaccines. This knowledge is important for establishing the best vaccination strategy.

Immunosuppressed non-responders to two doses of mRNA SARS-CoV-2 vaccines achieve an immune response comparable to those of immunocompetent individuals after a third dose.

The SARS-CoV-2 vaccines trigger the production of neutralizing antibodies to the SARS-CoV-2 spike (S) protein and induce a T cell-mediated immune response. However, the antibody titers that confer protection against the SARS-CoV-2 virus are currently not well-established. While immunocompetent individuals achieve a high level of immune response after SARS-CoV-2 vaccination, it now appears that a high proportion of immunosuppressed or immunocompromised, patients exhibit low or no response to two doses of the vaccines. Most non-responders are on treatment with either glucocorticoids, mycophenolate-mofetil (MMF), the anti-CD20 monoclonal antibody rituximab, calcineurin inhibitors like cyclosporine and tacrolimus, rapamycin (mTOR) signaling cascade inhibitors (i.e., sirolimus and everolimus), azathioprine, or methotrexate given for a variety of diseases including autoimmune disorders, hematological malignancies, and solid cancers, while recipients of solid organ transplants also fall within this category. Recently, several published reports have suggested that a third dose of these vaccines induces an elevated antibody response against the SARS-CoV-2 S protein.