SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes with implications for booster strategies

Abstract

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

mRNA BNT162b Vaccine Elicited Higher Antibody and CD4+ T-Cell Responses than Patients with Mild COVID-19

“…The B-and T-cell responses elicited by the mRNA BNT162b2 vaccine have a crucial role in the protection from SARS-CoV-2 infection and disease and in the establishment of a long-term memory response. In agreement with other studies [18][19][20][21][22], our data confirmed that the antibody levels were higher after the second dose of vaccine, but decreased after six months. We also observed that vaccinated subjects developed antibody levels similar to those of post-COVID-19 patients with pneumonia, but higher than those of mild-COVID-19 patients.…”

“…Although not significant, we also observed a trend towards a higher CD4 + T-cell proliferative response in vaccinated subjects than in mild-COVID-19 patients. However, we observed that the antibody levels decreased six months after vaccination, as reported by other studies [18][19][20][21][22], and required a booster dose to be restored to the initial levels. On the contrary, the CD4 + (but not CD8 + ) T-cell proliferative response did not decline six months after the vaccine, but remained at the same high levels of the post-COVID-19 patients with pneumonia.…”

“…The B-and T-cell responses elicited by the vaccine have a crucial role in the protection from SARS-CoV-2 infection and disease and in the establishment of a long-term memory response. Vaccinated subjects developed Nt Ab and specific T-cell responses after two doses [17], and several studies analysed the persistence of immune response until 6-8 months post-vaccination [18][19][20][21][22]. The immune response post-vaccination and post-infection was compared in IC patients up to 90 days from the vaccine [23], but a comparison of the long-term duration of the specific immune response after vaccination or infection has not been described.…”

IgG Anti-Spike Antibodies and Surrogate Neutralizing Antibody Levels Decline Faster 3 to 10 Months After BNT162b2 Vaccination Than After SARS-CoV-2 Infection in Healthcare Workers

“…Waning of antibody levels after vaccination, with concomitant reductions in protective immunity, have been demonstrated in clinical trials as well as in epidemiological studies ( 4 , 7 , 27 – 29 ). In HCW, IgG anti-S antibody levels peak around 3 weeks after the second dose of BNT162b2, followed by a decline over time ( 19 ).…”

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components

“…In the last two years, many studies on vaccinated subjects or patients who recovered from SARS-CoV-2 infection ( 1 – 3 ) highlighted the formation of high amounts of specific antibodies, a sign of robust protective immune responses and memory. A conspicuous number of studies reported that humoral and cellular immunity to SARS-CoV-2 reaches the peak after one month from vaccination, and then it decreases over time ( 4 – 7 ). Conversely, circulating specific memory B lymphocytes reach the peak after two/three months and remain constant over 8 months ( 1 , 2 ).…”