RESUMO
Two messenger RNA (mRNA)-based vaccines are widely used globally to prevent coronavirus disease 2019 (COVID-19). Both vaccine formulations contain PEGylated lipids in their composition, in the form of polyethylene glycol [PEG] 2000 dimyristoyl glycerol for mRNA-1273, and 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide for BNT162b2. It is known that some PEGylated drugs and products for human use that contain PEG, are capable of eliciting immune responses, leading to detectable PEG-specific antibodies in serum. In this study, we determined if any of the components of mRNA-1273 or BNT162b2 formulations elicited PEG-specific antibody responses in serum by enzyme linked immunosorbent assay (ELISA). We detected an increase in the reactivity to mRNA vaccine formulations in mRNA-1273 but not BNT162b2 vaccinees sera in a prime-boost dependent manner. Furthermore, we observed the same pattern of reactivity against irrelevant lipid nanoparticles from an influenza virus mRNA formulation and found that the reactivity of such antibodies correlated well with antibody levels against high and low molecular weight PEG. Using sera from participants selected based on the vaccine-associated side effects experienced after vaccination, including delayed onset, injection site or severe allergic reactions, we found no obvious association between PEG antibodies and adverse reactions. Overall, our data shows a differential induction of anti-PEG antibodies by mRNA-1273 and BNT162b2. The clinical relevance of PEG reactive antibodies induced by administration of the mRNA-1273 vaccine, and the potential interaction of these antibodies with other PEGylated drugs remains to be explored.
RESUMO
Tracking the emergence and spread of SARS-CoV-2 is critical to inform public health interventions. Phylodynamic analyses have quantified SARS-CoV-2 migration on global and local scales1-5, yet they have not been applied to determine transmission dynamics in Canada. We quantified SARS-CoV-2 migration into, within, and out of Canada in the context of COVID-19 travel restrictions. To minimize sampling bias, global sequences were subsampled with probabilities corrected for their countries monthly contribution to global new diagnoses. A time-scaled maximum likelihood tree was used to estimate most likely ancestral geographic locations (country or Canadian province), enabling identification of sublineages, defined as introduction events into Canada resulting in domestic transmission. Of 402 Canadian sublineages identified, the majority likely originated from the USA (54%), followed by Russia (7%), India (6%), Italy (6%), and the UK (5%). International introductions were mostly into Ontario (39%) and Quebec (38%). Among Pango lineages6, B.1 was imported at least 191 separate times from 11 different countries. Introduction rates peaked in late March then diminished but were not eliminated following national interventions including restrictions on non-essential travel. We further identified 1,380 singleton importations, international importations that did not result in further sampled transmission, whereby representation of lineages and location were comparable to sublineages. Although proportion of international transmission decreased over time, this coincided with exponential growth of within-province transmission - in fact, total number of sampled transmission events from international or interprovincial sources increased from winter 2020 into spring 2020 in many provinces. Ontario, Quebec, and British Columbia acted as sources of transmission more than recipients, within the caveat of higher sequence representation. We present strong evidence that international introductions and interprovincial transmission of SARS-CoV-2 contributed to the Canadian COVID-19 burden throughout 2020, despite initial reductions mediated by travel restrictions in 2020. More stringent border controls and quarantine measures may have curtailed introductions of SARS-CoV-2 into Canada and may still be warranted. Significance StatementBy analyzing SARS-CoV-2 genomes from Canada in the context of the global pandemic, we illuminate the extent to which the COVID-19 burden in Canada was perpetuated by ongoing international importations and interprovincial transmission throughout 2020. Although travel restrictions enacted in March 2020 reduced the importation rate and proportion of transmission from abroad across all Canadian provinces, SARS-CoV-2 introductions from the USA, India, Russia, and other nations were detectable through the summer and fall of 2020.
