FIG 1.

The impact of OAS on the efficacy of the immune response. OAS is affected not only by the temporality of an antigenic exposure but also by the “collection” of antigens associated with the exposure. (A) Exposure to hCoVs (related viruses such as HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-HKU1) primes the immune system to the Blue, Purple, and Green antigens. This will result in long-lived memory B cells with specificities to these antigens, respectively. Reexposure to hCoVs will result in a robust antibody response to each of these antigens. SARS-CoV-2 expresses the same hCoV Green antigen and two new antigens, Yellow and Red. The memory anti-Green B cell response will prevent or significantly limit the ability of naive B cells with specificities to Yellow and Red antigens from developing. In this scenario, the anti-Green antibody is protective; so, while OAS prevented/diminished the elicitation of antibodies with specificities to the Yellow and Red antigens, the anti-Green antigen memory response confers some level of protection against a SARS-CoV-2 infection. (B) This scenario is identical to that described for panel A with the exception that the anti-Green response elicited against hCoV is nonneutralizing for SARS-CoV-2. In this example, the memory response to Green is nonprotective while simultaneously inhibiting/interfering with the ability to mount a new response to the Yellow and Red antigens that could potentially provide protection. (C) This scenario depicts two separate exposures. Since no antigens are shared between hCoVs and SARS-CoV-2, the anti-SARS-CoV-2 response will be a primary exposure, unaffected positively or negatively by prior exposure to hCoVs.