Original antigen sin and COVID-19: implications for seasonal vaccination

McCarthy, Matthew W

doi:10.1080/14712598.2022.2137402

Cited by 8 publications

(8 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The concept of immune imprinting, also known as the original antigenic sin, is the immune system’s propensity to limit its response to new variant antigens after responding to the original antigen 15 . The consequence of this phenomenon is that the immune system cannot mount more effective responses following new variant infections or vaccines resembling the original immunogen.…”

Section: Introductionmentioning

confidence: 99%

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

Pérez-Alós,

Hansen,

Almagro Armenteros

et al. 2023

Nat Commun

View full text Add to dashboard Cite

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.

show abstract

Section: Introductionmentioning

confidence: 99%

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

Pérez-Alós,

Hansen,

Almagro Armenteros

et al. 2023

Nat Commun

View full text Add to dashboard Cite

show abstract

“…We examined individuals who had received only mRNA WT-directed monovalent vaccines, then experienced an Omicron infection, and then provided a blood sample. We investigated the antigenic sin hypothesis, which hypothesizes that more WT-based vaccines prior to an Omicron infection would lead to a relatively attenuated Omicron-specific humoral immune response postinfection ( 17 ). Our findings, however, revealed that more WT-based vaccines were associated with an enhanced Omicron-specific immune response, as measured by the ACE-2 inhibition to BA.4/5 Omicron Ag.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation

Asamoah-Boaheng,

Grunau,

Karim

et al. 2024

ImmunoHorizons

View full text Add to dashboard Cite

Recent research has highlighted the Omicron variant’s capacity to evade immune protection conferred by wild-type (WT) mRNA vaccines. Despite this observation, the potential involvement of antigenic sin phenomena remains unclear. Our hypothesis posited that a greater number of prior WT vaccine doses might lead to reduced anti-Omicron neutralization Abs following Omicron infection. To investigate this, we analyzed blood samples from human participants in the COVID-19 Occupational Risk, Seroprevalence, and Immunity among Paramedics (CORSIP) study who had received at least one WT mRNA vaccine before contracting Omicron. The exposure variable was the number of WT mRNA vaccines administered, and the outcome was the angiotensin-converting enzyme 2 (ACE-2) percent inhibition specific to the BA.4/BA.5 Omicron Ag. Contrary to expectations, our findings revealed that more WT-based vaccines were associated with an enhanced Omicron-specific immune response.

show abstract

“…These mutations, mostly concentrated in the vicinity of the receptor-binding domain (RBD), create constant opportunities for the generation of new escape variants (i.e., those that evade neutralizing antibodies), thus enabling immune evasion in subsequent vaccinations. Second, confrontation with novel antigens on escape variants is associated with “original antigenic sin”, the production of cross-reactive antibodies that may not be effective against the new antigen or pathogen due to prior exposure to predecessor strains [ 232 , 233 ]. Although cross-neutralization is a rare event, cross-reactivity in antibody binding to S-protein is common in the context of SARS-CoV-2 infection [ 234 ].…”

Section: Reviewmentioning

confidence: 99%

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Mead,

Seneff,

Wolfinger

et al. 2024

Cureus

View full text Add to dashboard Cite

Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

show abstract

Original antigen sin and COVID-19: implications for seasonal vaccination

Cited by 8 publications

References 76 publications

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

Investigating the Antibody Imprinting Hypothesis among Canadian Paramedics after SARS-CoV-2 Omicron Variant Circulation

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Contact Info

Product

Resources

About