Neutralizing antibody activity against the B.1.617.2 (delta) variant 8 months after two-dose vaccination with BNT162b2 in health care workers

Abstract

Objectives Humoral immunity wanes over time after two-dose BNT162b2 vaccination. Emerging variants of concern, such as the B.1.617.2 (delta) variant, are increasingly responsible for breakthrough infections due to their higher transmissibility and partial immune escape. Longitudinal data on neutralization against the B.1.617.2 (delta) variant are urgently needed to guide vaccination strategies. Methods In this prospective longitudinal observational study, anti-S1 IgG and neutralizing surrogate antibodies were measured in 234 collected samples from 60 health care workers after two-dose vaccination with BNT162b2 at five different time points over an 8-month period. In addition, antibodies against various SARS-CoV-2 epitopes, neutralization against wild-type, and cross-neutralization against the B.1.617.2 (delta) variant using a live virus assay were measured 6 weeks (second time point) and 8 months (last time point) after first vaccine dose. Results Median (IQR) anti-S1 IgG, surrogate neutralizing, and receptor-binding domain antibodies decreased significantly from a maximum level of 147 (102–298), 97 (96–98), and 20,159 (19,023–21,628) to 8 (4–13), 92 (80–96), and 15,324 (13,055–17,288) at the 8-month follow-up, respectively ( P <0.001 for all). Neutralization against the B.1.617.2 (delta) variant was detectable in 36/36 (100%) participants 6 weeks and in 50/53 (94%) participants 8 months after first vaccine dose. Median (IQR) ID 50 as determined by a live virus assay decreased from 160 (80–320) to 40 (20–40) ( P <0.001). Conclusions Although humoral immunity wanes over time after two-dose BNT162b2 vaccination in healthy individuals, most individuals still had detectable neutralizing activity against the B.1.617.2 (delta) variant after 8 months.

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium

“…At time of infection, individuals affected with the alpha VoC showed diminished but clearly detectable pseudovirus neutralization against D614G, while only two of the eight subjects with a BTI caused by the delta VoC had minimal residual activity against delta (Figure 7f,g). This was in contrast with the study performed by Benning et al [87], who showed detectable live virus neutralization against the delta VoC up to 8 months after vaccination in 94% of the participants. Additionally, Evans et al [88] showed detectable but diminishing neutralization capacity against D614G, alpha, beta, delta and omicron VoCs up to 6 months BNT162b2 vaccination.…”

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

“…The waning of vaccine-induced immunity has been attributed to declining anti-S antibody levels and the emergence of variants of concern (VOC). Anti-S antibody levels start to decline 2-3 months after vaccination, declining continuously up to 8 months after vaccination ( 6 – 8 ). A similar continuous decline has been observed for anti-S and anti-N antibodies after natural infection ( 9 , 10 ).…”

Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients

“…A strong correlation between commercially available tests and live‐virus neutralization has been described previously by us and others in different cohorts. 20 , 26 , 27 , 58 , 59 , 60 …”

“… 63 These data provide cause for optimism at a time of rising incidence and waning humoral immunity at least for the general population. 58 , 63 Regarding kidney transplant recipients, Schrezenmeier et al found significantly increased spike‐reactive CD4 + T helper cells with higher portions of IL‐2 and IL‐4 secreting and polyfunctional (IFN y + TNFα + IL‐2 + ) T cells in seroconverted kidney transplant recipients after a third vaccine dose, however, non‐responders showed only marginal improvements in antigen‐specific B and T cells. 65 …”

“…Humoral immune response was assessed in 49 kidney transplant recipients and 25 age-matched healthy controls. Median (IQR) age was 55 (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65) for kidney transplant recipients and 53 (39-59) years for healthy controls. With 20/49 (41%) kidney transplant recipients and 17/25 (68%) healthy female controls, the healthy controls cohort consisted of more females (p = .048).…”