Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications

Abstract

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.

Keywords: COVID 19 vaccine; SARS-COV-2 variants; clinical application; neutralizing antibodies; protective role.

Figure 1

Schematic diagram of NAb-mediated protective mechanisms against SARS-CoV-2 infection. (A) Neutralization mechanisms: Following the binding of NAbs (via Fab) to the RBD of the S1 subunit of SARS-CoV-2, the virus-antibody complex is formed, which prevents the viral binding to host receptor (ACE2) or coreceptors (TMPRSS2, NRP1 etc.) or changes the conformation of the S protein to block viral entry into host cells, thereby preventing subsequent membrane fusion or infection. (B) Effector mechanisms: The binding of antibody-bound infected host cells (via MHC and Fc) to the FcγR of the immune cells and complements (C1q) trigger several effector mechanisms to kill the virus infected cells. In the CDC pathway, complement activates the classical complement pathway and induces cell death by the formation of MAC. On the other hand, phagocytes interact with MHC and result in phagocytosis of infected cells via ADCP. Similarly, the interaction of FcγR-expressing NK cells with the Fc of the antibody complex leads to cytotoxic granule release (GZM and perforin) and hence cytolysis (ADCC). ACE2, Angiotensin-converting enzyme 2; ADCC, Antibody-dependent cellular cytotoxicity; ADCP, Antibody-dependent cellular phagocytosis; CDC, complement-dependent cytotoxicity; Fab, fragment antigen-binding region; Fc, crystallizable fragment; FcγR, Fc gamma receptor; GZM, Granzyme; MAC, Membrane attack complex; MHC, major histocompatibility complex; NAbs, Neutralizing antibodies; NK, Natural killer cell; NRP1, neuropilin 1;TMPRSS2, transmembrane serine protease 2.