Different decay of antibody response and VOC sensitivity in naïve and previously infected subjects at 15 weeks following vaccination with BNT162b2

Abstract

Background COVID-19 vaccines have demonstrated effectiveness in reducing SARS-CoV-2 mild and severe outcomes. In vaccinated subjects with SARS-CoV-2 history, RBD-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single BTN162b2 vaccine dose to higher levels than those in naïve recipients after the second dose, irrespective of waning immunity. In this study, we inspected the long-term kinetic and neutralizing responses of S-specific IgG induced by two administrations of BTN162b2 vaccine in infection-naïve subjects and in subjects previously infected with SARS-CoV-2. Methods Twenty-six naïve and 9 previously SARS-CoV-2 infected subjects during the second wave of the pandemic in Italy were enrolled for this study. The two groups had comparable demographic and clinical characteristics. By means of ELISA and pseudotyped-neutralization assays, we investigated the kinetics of developed IgG-RBD and their neutralizing activity against both the ancestral D614G and the SARS-CoV-2 variants of concern emerged later, respectively. The Wilcoxon matched pair signed rank test and the Kruskal–Wallis test with Dunn’s correction for multiple comparison were applied when needed. Results Although after 15 weeks from vaccination IgG-RBD dropped in all participants, naïve subjects experienced a more dramatic decline than those with previous SARS-CoV-2 infection. Neutralizing antibodies remained higher in subjects with SARS-CoV-2 history and conferred broad-spectrum protection. Conclusions These data suggest that hybrid immunity to SARS-CoV-2 has a relevant impact on the development of IgG-RBD upon vaccination. However, the rapid decay of vaccination-elicited antibodies highlights that the administration of a third dose is expected to boost the response and acquire high levels of cross-neutralizing antibodies.

Hybrid Immunity Shifts the Fc-Effector Quality of SARS-CoV-2 mRNA Vaccine-Induced Immunity

“…Real-world vaccine efficacy revealed rapidly waning immunity following vaccination ( 16 – 18 ), prompting recommendations for booster vaccine doses 4 to 6 months following the primary vaccine series ( 19 , 20 ). However, anecdotal studies have suggested fewer vaccine breakthroughs ( 21 – 24 ) and a slower decay in the antibody response ( 25 ) among individuals who had previously experienced COVID-19 prior to vaccination. Moreover, deeper immunological profiling indicated increased breadth and magnitude of the neutralizing antibody response in individuals with hybrid (infection + vaccination) compared to vaccine-only induced immunity ( 26 – 31 ).…”

Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity

“…Real world vaccine efficacy revealed rapidly waning immunity following vaccination [16][17][18] prompting recommendations for booster vaccine doses 4 to 6 months following the primary vaccine series 19,20 . However, anecdotal studies suggested fewer vaccine breakthroughs [21][22][23][24] and a slower decay in the antibody response 25 among individuals who had previously experienced COVID-19 prior to vaccination. Moreover, deeper immunological profiling pointed to increased breadth and magnitude of the neutralizing antibody response in individuals with hybrid (infection + vaccination) compared to vaccine-only induced immunity [26][27][28][29][30][31] .…”

Strong neutralizing antibody responses to SARS-CoV-2 variants following a single vaccine dose in subjects with previous SARS-CoV-2 infection

“…Previous studies have shown no increase in circulating antibodies, neutralizing titers or antigen-specific memory B cells after more than one dose of vaccine in those with previous infection [8, 15, 16]. Hybrid immunity-induced antibody concentrations and NAbs have been shown to decline with time but remain at a higher level than in uninfected vaccinated individuals for at least three months [8, 11, 17]. Furthermore, hybrid immunity has been associated with a somewhat lower risk of reinfection and hospitalization compared to immunity induced solely by previous infection [18-20].…”

“…The Omicron variant carries several mutations in the RBD [5,6] and has rapidly given rise to major epidemic waves worldwide since late 2021, also causing breakthrough infections in vaccinated individuals. COVID-19 vaccination after recovery from SARS-CoV-2 infection (hybrid immunity) has been reported to induce comparable or higher S-specific antibody levels and NAb titers than in twice vaccinated SARS-CoV-2 naïve individuals [7][8][9][10][11][12]. In addition, vaccination has been shown to elicit immunity with broader specificity and increase the neutralization potency against SARS-CoV-2 variants in previously infected individuals [13,14].…”