Novel universal SARS-CoV DNA vaccine inducing neutralizing antibodies to huCoV-19/WH01, Beta, Delta and Omicron variants and T cells to Bat-CoV (preprint)

The SARS-CoV-2 pandemic is constantly changing with new variants appearing that are more contagious (Alpha and Delta), evade the neutralising antibody (NAb) response (Beta), or both (Omicron). This is a challenge for vaccine development. We generated a novel universal SARS-CoV-2 DNA vaccine containing the receptor binding domain (RBD) loops from the original huCoV-19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins from the huCoV-19/WH01 strain. This vaccine induced high levels of spike antibodies that crossreacted between the huCoV-19/WH01, Beta, and Delta spike proteins, and neutralized the huCoV-19/WH01, Beta, Delta and Omicron virus in vitro. The vaccine induced T cells to all vaccine proteins in mice and rabbits that recognized Bat-CoV N sequences. Finally, the vaccine protected K18 mice against lethal SARS-CoV-2 Beta variant infection, whereas only priming N-specific T cells was 60% protective. This universal SARS-CoV vaccine candidate induces a uniquely broad functional immunity.

Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis (preprint)

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization seems to affect the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.