SARS-CoV-2 vaccination in the context of original antigenic sin

Abstract

Immunological memory is the ability of the adaptive immune system to ensure a persistent protective effect after immunization. However, it can also be a limitation to building a sufficient level of protective antibodies specific to new mutations of the virus. It is imperative to bear this phenomenon (called "original antigenic sin") in mind and make every effort to overcome its inherent pitfalls when updating current and designing new vaccines.

Broad neutralization against SARS-CoV-2 variants induced by ancestral and B.1.351 AS03-Adjuvanted recombinant Plant-Derived Virus-Like particle vaccines

“…However, induction of very high initial titers is likely desirable since it is well-documented that antibody titers wane substantially with time after both natural disease and vaccination [76] . These observations are similar to the results recently released by others [72] , [77] [Pfizer, Novavax] but distinct from those reported by Moderna [71] in that no evidence of original antigenic sin was noted [78] . Since these animals only received two doses, it is currently unknown how humoral response against VOCs would be influenced by a third (booster) dose but others have reported very high and cross-protective neutralizing antibody responses both in animals [64] , [71] and human trials [65] , [79] , [80] after this additional dose.…”

Back to the Future: Immune Protection or Enhancement of Future Coronaviruses

“…Those antibodies could bind to the new strain but not neutralize the virus [ 71 ]. This phenomenon needs to be considered when designing and evaluating current and future coronavirus vaccines [ 72 ]. Current data do not point toward a role for “original antigenic sin” in the immune response to SARS-CoV-2 infection or vaccination [ 73 , 74 ].…”

Comprehending B-Cell Epitope Prediction to Develop Vaccines and Immunodiagnostics

“…Immunodominance may thus be precluded by immune tolerance (i.e., selective inability to mount immune responses to particular BCEs, due to functional deletion or inactivation of their corresponding B cells), which is often induced by BCEs of host self antigens (i.e., autoantigens) and of other antigens (e.g., in food) to which the host has been exposed in a natural physiologic setting (rather than in the course of infectious disease or vaccination) ( 38 – 40 ). Alternatively, immunodominance may be heightened by the immunological memory of prior immunization (e.g., via infection or vaccination), as occurs in the phenonenon of original antigenic sin (i.e., antigenic imprinting) whereby memory B-cell clones generated by past immunization continue to dominate antibody responses to more recent immunizations, possibly even compromising the ability to mount protective immune responses against newly encountered pathogen variants ( 41 , 42 ). From an evolutionary standpoint, pathogens may co-evolve with their hosts to evade immune destruction in part by altering their BCE repertoires to limit the expression of immunodominant pathogen BCEs on key virulence factors (e.g., via molecular mimicry, with pathogen BCEs tending to resemble host self BCEs) while possibly also expressing immunodominant pathogen BCEs that serve as antigenic decoys to detract from protective host immune responses ( 43 ).…”