SARS-CoV-2 structural features may explain limited neutralizing-antibody responses

Neutralizing antibody responses of SARS-CoV-2-infected patients may be low and of short duration. We propose here that coronaviruses employ a structural strategy to avoid strong and enduring antibody responses. Other viruses induce optimal and long-lived neutralizing antibody responses, thanks to 20 or more repetitive, rigid antigenic epitopes, spaced by 5-10nm, present on the viral surface. Such arrays of repetitive and highly organized structures are recognized by the immune system as pathogen-associated structural patterns (PASPs), which are characteristic for pathogen surfaces. In contrast, coronaviruses are large particles with long spikes (S protein) embedded in a fluid membrane. Therefore, the neutralizing epitopes (which are on the S protein) are loosely "floating" and widely spaced by an average of about 25nm. Consequently, recruitment of complement is poor and stimulation of B cells remains suboptimal, offering an explanation for the inefficient and short-lived neutralizing antibody responses.