ABSTRACT
Background: While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them in a context of vaccine scarcity. This decision raised concerns about vaccine efficacy, notably against the many circulating variants. In this study, we analyzed the longitudinal humoral responses from before the first dose to 4 months after the second dose in a cohort of SARS-CoV-2 naïve and previously infected (PI) individuals, with an interval of sixteen weeks between the two doses. We compared these responses to those elicited in individuals receiving the three weeks dose interval. Methods: We measured the level of antibodies recognizing SARS-CoV-2 Spike or its receptor-binding domain, and the capacity of these antibodies to neutralize several variants of concern (VOCs) and other human coronaviruses. We also measured B cell responses and Fc-mediated effector functions (ADCC) elicited by vaccination. Results: We observed that in PI individuals, the first dose led to strong humoral responses that could not be significantly improved further upon administration of a second dose. In the naïve individual's group, the first dose induced weak neutralizing activity but strong Fc-mediated functions and the administration of the second dose 16 weeks after led to a significant increase of humoral responses, achieving similar levels to those measured in PI individuals. In both groups, we observed that plasmas were able to recognize and neutralize the Spike of different VOCs but also SARS-CoV-1. Conclusion: Our results show that individuals that received the extended BNT162b2 vaccine interval developed strong humoral responses. For the naïve donors, these responses were superior to those elicited by the three-week dose interval and comparable to the PI responses after one or two doses.
ABSTRACT
Background: The rapid emergence of SARS-CoV-2 variants is fueling the recent waves of the COVID-19 pandemic. Recently identified Mu (B.1.621) and A.2.5 variants carry some mutations shared by other variants of concerns (VOCs). For example, N501Y and E484K mutations in the receptor-binding domain (RBD) domain detected in B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) are now present within the Mu variant. Similarly, the L452R mutation of B.1.617.2 (Delta) variant is now present in A.2.5. Here, we evaluated the capacity of Mu and A.2.5 Spikes to interact with angiotensin-converting enzyme 2 (ACE2) and performed binding and neutralization assays with plasma from vaccinated individuals. In addition, to better understand their antigenic properties, we compared both Mu and A.2.5 with Alpha, Beta, Gamma and Delta VOCs Spikes. Methods: Cells expressing the different Spikes were interrogated for their capacity to interact with the ACE2 receptor using a recombinant ACE2-Fc recombinant protein. We also evaluated their recognition by plasma from BNT162b2 vaccinated individuals. Biolayer interferometry (BLI) was used to measure the binding kinetics of selected RBD mutants to soluble ACE2 (sACE2). Finally, we evaluated the susceptibility of pseudoviral particles bearing the different Spikes to neutralization by plasma from vaccinated individuals. Results: All SARS-CoV-2 S-glycoprotein variants were recognized less efficiently by plasma from vaccinated SARS-CoV-2 naïve and previously-infected individuals compared to D614G Spike with the exception of B.1.1.7 S-glycoprotein. Enhanced ACE2 interaction by the Spikes tested was associated with a decrease in the off-rate of the ACE2-RBD interaction. Pseudoviral particles bearing the Spike of Mu variant were similarly neutralized by plasma from vaccinated individuals than those carrying the Beta and Delta Spikes. Conclusion: Plasma from vaccinated SARS-CoV-2 naïve and previously-infected individuals efficiently recognized all the Spikes tested. The decreased neutralization susceptibility of pseudoviral particles expressing the Mu Spike was similar to Beta and Delta, thus underscoring the importance of functionally tracking emerging variants. In summary, our results highlight the importance of measuring critical parameters such as ACE2 interaction, plasma recognition and neutralization from each emerging variant.
ABSTRACT
The rapid dynamics of COVID-19 calls for quick and effective tracking of virus transmission chains and early detection of outbreaks, especially in the “phase 2” of the pandemic, when lockdown and other restriction measures are progressively withdrawn, in order to avoid or minimize contagion resurgence. For this purpose, contact-tracing apps are being proposed for large scale adoption by many countries. A centralized approach, where data sensed by the app are all sent to a nation-wide server, raises concerns about citizens’ privacy and needlessly strong digital surveillance, thus alerting us to the need to minimize personal data collection and avoiding location tracking. We advocate the conceptual advantage of a decentralized approach, where both contact and location data are collected exclusively in individual citizens’ “personal data stores”, to be shared separately and selectively (e.g., with a backend system, but possibly also with other citizens), voluntarily, only when the citizen has tested positive for COVID-19, and with a privacy preserving level of granularity. This approach better protects the personal sphere of citizens and affords multiple benefits: It allows for detailed information gathering for infected people in a privacy-preserving fashion;and, in turn this enables both contact tracing, and, the early detection of outbreak hotspots on more finely-granulated geographic scale. The decentralized approach is also scalable to large populations, in that only the data of positive patients need be handled at a central level. Our recommendation is two-fold. First to extend existing decentralized architectures with a light touch, in order to manage the collection of location data locally on the device, and allowthe user to share spatio-temporal aggregates-if and when they want and for specific aims-with health authorities, for instance. Second, we favour a longerterm pursuit of realizing a Personal Data Store vision, giving users the opportunity to contribute to collective good in the measure they want, enhancing self-awareness, and cultivating collective efforts for rebuilding society. © 2020, University of Skovde. All rights reserved.