The COVID-19 pandemic catalyzed a revolution in vaccine development, leading to the testing and approval of several global vaccine platforms that have shown tremendous promise in curbing the pandemic. Yet, despite these successes, waning immunity, and the emergence of variants of concern linked to rising breakthrough infections among vaccinees, have begun to highlight opportunities to improve vaccine platforms and deployment. Real-world vaccine efficacy has highlighted the reduced risk of breakthrough infection and disease among individuals infected and vaccinated, otherwise referred to as hybrid immunity. The hybrid immunity points to the potential for more vigorous or distinct immunity primed by the infection and may confer enhanced protection from COVID-19. Beyond augmented hybrid induced neutralizing antibody and T cell immune responses, here we sought to define whether hybrid immunity may shape the functional humoral immune response to SARS-CoV-2 following Pfizer/BNT162b2 and Moderna mRNA1273 mRNA-based, and ChadOx1/AZ1222 and Ad26.COV2.S vector-based SARS-CoV-2 vaccination. Each vaccine exhibited a unique functional humoral immune profile in the setting of naive or hybrid immunity. However, hybrid immunity showed a unique augmentation in S2-domain specific functional humoral immunity that was poorly induced in the setting of naive immune response. These data highlight the immunodominant effect of the S1-domain in the setting of natural immunity, which is highly variable during viral evolution, and the importance of natural infection in breaking this immunodominance in driving immunity to the S2 region of the SARS-CoV-2 S2 domain that is more conserved across variants of concern.
is currently an employee of Moderna Therapeutics and holds equity in Leyden Labs and Systems Seromyx. All experiments, analyses, and interpretations of the data in this study GA participated in predated her employment at Moderna. SKG reports grant support through his institution from Kowa Pharmaceuticals America Inc., Gilead Sciences Inc., and ViiV Healthcare for the conduct of the study; grants from Theratechnologies and Navidea; personal fees from Theratechnologies and ViiV; and service on the Scientific Advisory Board of Marathon Asset Management.
Despite the success of existing COVID-19 vaccine platforms, the persistent limitations in global deployment of vaccines and waning immunity exhibited by many of the currently deployed vaccine platforms have led to perpetual outbreaks of SARS-CoV-2 variants of concern. Thus, there is an urgent need to develop new durable vaccine candidates, to expand the global vaccine pipeline, and provide safe and effective solutions for every country worldwide. Here we deeply profiled the functional humoral response induced by two doses of AS03-adjuvanted and non-adjuvanted plant-derived Coronavirus-like particle (CoVLP) vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination. AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months.
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