Natural killer cell‐mediated ADCC in SARS‐CoV‐2‐infected individuals and vaccine recipients

Abstract

COVID‐19, caused by SARS‐CoV‐2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID‐19 remains less well understood. Here, we characterized NK cell‐mediated SARS‐CoV‐2 antibody‐dependent cellular cytotoxicity (ADCC) against SARS‐CoV‐2 spike‐1 (S1) and nucleocapsid (NC) protein. Serum samples from SARS‐CoV‐2 resolvers induced significant CD107a‐expression by NK cells in response to S1 and NC, while serum samples from SARS‐CoV‐2‐negative individuals did not. Furthermore, serum samples from individuals that received the BNT162b2 vaccine induced strong CD107a expression by NK cells that increased with the second vaccination and was significantly higher than observed in infected individuals. As expected, vaccine‐induced responses were only directed against S1 and not against NC protein. S1‐specific CD107a responses by NK cells were significantly correlated to NK cell‐mediated killing of S1‐expressing cells. Interestingly, screening of serum samples collected prior to the COVID‐19 pandemic identified two individuals with cross‐reactive antibodies against SARS‐CoV‐2 S1, which also induced degranulation of NK cells. Taken together, these data demonstrate that antibodies induced by SARS‐CoV‐2 infection and anti‐SARS‐CoV‐2 vaccines can trigger significant NK cell‐mediated ADCC activity, and identify some cross‐reactive ADCC‐activity against SARS‐CoV‐2 by endemic coronavirus‐specific antibodies.

Augmenting vaccine efficacy against delta variant with ‘Mycobacterium-w’ mediated modulation of NK-ADCC and TLR-MYD88 pathways

“…Amongst these, NK cell mediated ADCC is the most potent and consistent. While VOC might escape neutralization by mutational changes in the receptor binding domains, NK cell mediated ADCC effector functions is more resilient and remain preserved across the variants [14][15][16][17] for longer periods 18 .…”

A hybrid discrete-continuum model of immune responses to SARS-CoV-2 infection in the lung alveolar region, with a focus on interferon induced innate response

“…Once cells are infected, interferons also limit the assembly, replication, and shedding of infectious progeny McNab et al (2015) and Iyer et al (2017) . Specifically, interferons signal neighboring epithelial cells to increase the numbers of class I major histocompatibility complex proteins (or MHC class I) on their surface, enabling immune cells (macrophages, killer cells) to identify and eliminate the infected cell via phagocytosis or other cytotoxic factors Hagemann et al (2022) . In our model interferons are released at a prescribed rate by infected cells in the shedding phase; since we do not model macrophages explicitly, this rate includes the potential source of interferons from macrophages.…”

Role of IgM Memory B Cells and Spleen Function in COVID-19

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID- 19) pandemic, which has dramatically impacted our globalized society, with more than 500 million reported infections and more than6million deaths worldwide as of April 2022 (1). SARS-CoV-2 has been shown to elicit a strong immune activation mirrored by the so-called "cytokine storm" and the complex interaction between the virus and immune system contributes shaping the heterogenous landscape of COVID-19-related pathology, including lung, liver, skin and spleen or other lymphoid organ damage, among others, and of clinical manifestations (2,3).…”

“…B cells and antibody-mediated immunity have also been shown to play a prominent role against SARS-CoV-2, since a rapid appearance of virus-specific antibodies is observed in most individuals, and a high titre of neutralizing antibodies to the spike protein and its receptor binding domain (RBD) have been found to confer protection both in humans and animal models ( 9 ). Moreover, other antiviral activities of antibodies, including fraction constant (Fc)-effector related-functions, such as antigen-dependent cell-mediated cytotoxicity (ADCC), are thought to play a role ( 3 ). In parallel, a compromised humoral development with attenuated IgG responses has been found to be associated with worse outcomes in acute patients with moderate-to-severe disease ( 5 ).…”