Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors

Abstract

Background: Although vaccines effectively prevent coronavirus disease 2019 in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy. Methods: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine. Findings: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-a) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFitreated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. Conclusions: Vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) will likely be required to prevent SARS-CoV-2 infection in this susceptible population.

Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice

“…The correlation was most linear for B.1.1.529-challenged animals (R 2 = 0.8155, P < 0.0001), with a minimum neutralizing titer of approximately 2,000 required to completely prevent infection at 6 dpi. Most of the breakthrough infections occurred with the lower 0.1 μg dose of mRNA vaccines, which models what might be occurring in immunocompromised or elderly individuals, or immunocompetent individuals at times remote from completion of their primary immunization series (Chen et al, 2021a; Choi et al, 2021; Evans et al, 2021).…”

Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19

“…Whether the phenomenon we report is associated with protection from viruses in patients with lupus or autoimmune disease is not known ( 29 ), but this could be confounded by the immunosuppressive treatments and other factors related to these conditions. In addition to reducing immune defense, immunosuppression may also blunt COVID-19 vaccination responses ( 30 , 31 ), but our samples were collected before vaccination was available. Most studies demonstrate a similar mortality rate in SLE patients as the general population in the setting of COVID-19 ( 29 ).…”

Favourable vaccine-induced SARS-CoV-2 specific T cell response profile in patients undergoing immune-modifying therapies

“…Others have already shown that these therapies, particularly TNF inhibitors, reduce the ability of different COVID-19 vaccines (based on mRNA or Adenoviral vector) to produce Spike-specific antibodies (5–8) and recognize SARS-CoV-2 variants including B.1.617.2 (Delta) (4). Such results are expected, since reduced humoral responses to other vaccines (i.e.…”

“…While these agents reduce disease burden and improve quality of life (1), they are broadly considered immunosuppressive. The COVID-19 pandemic and the necessity to implement widespread vaccination sparked debate and research on the impact of these chronic therapies on the immunogenicity of SARS-CoV-2 vaccination (2)(3)(4).…”