Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity

Abstract

Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m2) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight controls, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.

SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study

“…However, adequate glycaemic control after vaccination improved immunological responses and may even restore the protection against SARS-CoV-2 infection 31. We did not find an association between peak antibody levels with BMI, but a study in Scotland suggested that obesity could lead to faster waning of immunity after vaccination, which may explain increased disease severity from breakthrough infections in people with obesity 32. Previous studies also found that hypertension33 and smoking34 35 were associated with lower antibody responses post-vaccination; there was marginal evidence for a similar effect in our population (p=0.09; 0.12).…”

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles

“…The SARS-CoV-2 virus used in this study was the wildtype (lineage B) isolate SARS-CoV-2/human/Liverpool/REMRQ0001/2020, a kind gift from Ian Goodfellow (University of Cambridge, UK), isolated by Lance Turtle (University of Liverpool, UK) and David Matthews and Andrew Davidson (University of Bristol, UK) 92,93 ( Plasma was heat-inactivated at 56°C for 30 mins before use, and neutralizing antibody titers at 50% inhibition (NT50) measured as previously described. [94][95][96] In brief, luminescent HEK293T-ACE2-30F-PLP2 reporter cells (clone B7) expressing SARS-CoV-2 Papain-like protease-activatable circularly permuted firefly luciferase (FFluc) were seeded in flat-bottomed 96-well plates. The next day, SARS-…”

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

“…The SARS-CoV-2 virus used in this study was the wildtype (lineage B) isolate SARS-CoV-2/human/Liverpool/REMRQ0001/2020, a kind gift from Ian Goodfellow (University of Cambridge), isolated by Lance Turtle (University of Liverpool) and David Matthews and Andrew Davidson (University of Bristol) (Daly et al, 2020; Patterson et al, 2020)(Plasma was heat-inactivated at 56°C for 30 mins before use, and neutralizing antibody titres at 50% inhibition (NT 50 ) measured as previously described (Bergamaschi et al, 2021; Gerber et al, 2022; van der Klaauw et al, 2022). In brief, luminescent HEK293T-ACE2-30F-PLP2 reporter cells (clone B7) expressing SARS-CoV-2 Papain-like protease-activatable circularly permuted firefly luciferase (FFluc) were seeded in flat-bottomed 96-well plates.…”