Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

Abstract

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the post-boost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitope-specific responses, with higher RBD- and NTD- specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

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

“…56 Moreover, the BNT162b2 and mRNA1273 mRNA vaccines appear to induce different functional profiles in humans with higher RBD-and NTD-specific IgA as well as functional antibodies (ADNP and antibody-dependent natural killer cell activity [ADNK]) seen in mRNA-1273 vaccine recipients. 57 Thus, and independent of the lower neutralizing antibody levels observed in the sera of individuals with CID treated with TNFi, diminished Fc effector function profiles could also contribute to a higher frequency of breakthrough infections in this and other immunosuppressed vaccinated populations. [58][59][60] The lower serological responses to the BNT162b2 vaccine seen in many of the individuals with CID in our cohort appears the be worse against the two viruses with spike genes of B.1.351 and B.1.617.2.…”

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…In addition, a recent study still in pre-print format showed higher epitope spreading, IgA immunity and specific Ab function (i.e. enhanced Ab-dependent neutrophil phagocytosis and Ab-dependent NK cell degranulation) in patients vaccinated with the mRNA-1273 in comparison to the BNT162b vaccine (55). In concordance with the higher immunogenicity of mRNA-1273 vaccine, a recent study observed lower 24-week COVID-19 outcomes (defined as documented SARS-CoV-2 infection, symptomatic COVID-19, hospitalization and/or admission for ICU for COVID-19, or death from COVID-19) in persons vaccinated with the mRNA-1273 vaccine than in those given the BNT162b2 vaccine (56).…”

Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses

“…Durable antibody responses are mediated through memory B cells and long-lived plasmablasts. These subsets continuously produce neutralizing antibodies and non-neutralizing antibodies that will mobilize effector functions of innate immune cells such as antibody-dependent cellular cytotoxicity and antibody-dependent neutrophil phagocytosis 12,13 . This contributes to protection during acute infection and perhaps reduce the risk of reinfection.…”