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

Abstract

BackgroundIgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection.MethodsWe measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection (“infection”, n=83) or vaccination (2 doses of BNT162b2) with (“hybrid immunity”, n=17) or without prior SARS-CoV-2 infection (“vaccination”, n=97).ResultsThe humoral immune response in the “vaccination” cohort was higher at 3 months, but lower at 10 months, compared to the “infection” cohort due to a faster decline. The “hybrid immunity” cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the “vaccination” cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples.ConclusionsHybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.

Development of hybrid immunity during a period of high incidence of infections with Omicron subvariants: A prospective population based multi-region cohort study

“…These findings are in line with previous studies, conducted in small and non-population-based samples, showing that hybrid immunity can confer to antibodies a better neutralisation capacity. [24][25][26][27][28][29][30] This study is the first to demonstrate the extent of hybrid immunity and neutralisation capacity in the general population in 2022. It is likely that we underestimated hybrid immunity and that its prevalence is higher than 51%, as anti-nucleocapsid antibodies wane quickly and we likely missed some infections that occurred before 2022.…”

“…These findings are in line with previous studies, conducted in small and non-population-based samples, showing that hybrid immunity can confer to antibodies a better neutralisation capacity. 24–30…”

Comparative IgG responses to SARS-CoV-2 after natural infection or vaccination

“…However, whether a vaccine-induced NAb response provides an advantage over the longer term remains unclear. For example, in a previous evaluation of purely vaccine-induced NAb activity in 62 healthcare workers, which excluded cases of prior exposures or breakthrough infections, Decru et al found significant waning of neutralization activity 10 months after receiving a second dose of BNT162b2 (12). In contrast, here we observed an apparent rise in NAb titer over time (for up to 12 months since last reported dose) that was driven predominantly by samples in the vaccinated group.…”

“…However, vaccination campaigns were met with varying degrees of hesitancy in portions of the population (3)(4)(5). In the intervening months, researchers documented Immunoglobulin G (IgG) seroconversion and fluctuating levels of sustained immunity resulting from natural infection and/or vaccination (6)(7)(8)(9)(10)(11)(12)(13)(14)(15), and established a positive relationship between anti-spike antibodies and clinical protection from SARS-CoV-2 (16)(17)(18). However, the current literature does not provide a clear difference in antibody profiles acquired through vaccination and natural infection.…”

“…Prospective evaluations tend to be limited in sample size (12,14,(20)(21)(22), have short serological monitoring periods, (9,20,22) or analyses were completed retrospectively (23,24). Many studies utilize populations of healthcare workers who may encounter infectious agents -including SARS-CoV-2 -more frequently than other members of the community, limiting generalizability of results due to potential repeated exposures and subclinical infections (9,12,20,25). Several quality studies have evaluated the effectiveness of vaccination-and/or infection-acquired immunity over time, but have lacked a serological component (24)(25)(26).…”