The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of two doses BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19 recovered) compared to naïve subjects, we evaluated SARS-CoV-2 Spike-specific T and B cell responses, as well as specific IgA, IgG, IgM and neutralizing antibodies titers in 22 individuals who received BNT162b2 mRNA COVID-19 vaccine, 11 of which had a previous history of SARS-CoV-2 infection.Evaluations were performed before vaccination and then weekly until 7 days post second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19 recovered subjects without any additional improvement after the second dose. On the contrary, the second dose is proved mandatory in naïve ones to further enhance the immune response. These findings were further confirmed at serological level in a larger cohort of naïve (68) and COVID-19 recovered (29) subjects, tested up to 50 days post vaccination. These results question whether a second vaccine injection in COVID-19 recovered subjects is required and indicate that millions of vaccine doses may be redirected to naïve individuals, thus shortening the time to reach herd immunity.

The characterization of cell-mediated and humoral adaptive immune responses to SARS-CoV-2 is fundamental to understand COVID-19 progression and the development of immunological memory to the virus. In this study, we detected T-cells reactive to SARS-CoV-2 proteins M, S, and N, as well as serum virus-specific IgM, IgA, IgG, in nearly all SARS-CoV-2 infected individuals, but not in healthy donors. Virus-reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immunecheckpoint molecules PD1 and TIGIT. Of note, we detected antigen-specific adaptive immune response both in asymptomatic and symptomatic SARS-CoV-2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell-mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life-threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies.

The development of effective COVID-19 vaccines has been essential in slowing the spread of SARS-CoV-2. However, unvaccinated populations as well as those who do not respond to vaccination still remain at risk. Very few cancer patients were included in the COVID-19 mRNA vaccine trials and any individuals receiving chemotherapy or immunotherapy within 6 months were excluded. 1 Consequently, we have an inadequate knowledge of how well these vaccines work in the cancer patient population.However, by extrapolation from other vaccines, we hypothesized that patients with hematologic malignancies, especially those on E410 CORRESPONDENCE

BACKGROUND. Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 occurs via natural infection or vaccination. However, it is currently unknown how long infection-or vaccination-induced immunological memory will last. METHODS.We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to one year post infection and following mRNA vaccination in naïve and COVID-19 recovered individuals. RESULTS.We found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly especially in naïve subjects. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naïve subjects, while it results ineffective in previously SARS-CoV-2 infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to one year following natural infection in a cohort of unvaccinated individuals.CONCLUSION. Short-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4+ T cells may protect from severe disease development. A booster dose restores optimal anti-spike immunity in naïve subjects, while the need for vaccinated COVID-19 recovered subjects has yet to be defined. TRIAL REGISTRATION. na

Characterizing the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of two doses BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (ex COVID-19) compared to naive subjects we evaluated SARS-CoV-2 spike-specific T and B cell responses, as well as specific IgG, IgM and neutralizing antibodies titres in 22 individuals who received BNT162b2 mRNA COVID-19 vaccine, 11 of which had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days post second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in ex COVID-19 subjects without any additional improvement after the second dose. On the contrary, the second dose is mandatory in naive ones to further enhance the response. These results question whether a second vaccine jab in ex COVID-19 subjects is required and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.