Project description:A known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine is the only contraindication to coronavirus disease 2019 (COVID-19) mRNA vaccination. It is important for pediatricians to understand the likelihood of an allergic reaction to COVID-19 mRNA vaccines, including its excipients. Episodes concerning for anaphylaxis were immediately reported following early administration of COVID-19 mRNA vaccines to adults. Although allergic type symptoms were reported equally in recipients of placebos and test vaccines in phase 3 clinical trials, post-authorization prospective studies state that 0.2-2% of vaccine recipients have experienced allergic reactions. Subsequent allergy testing of affected individuals has focused largely on evaluation of allergic sensitization to a novel vaccine excipient, polyethylene glycol (PEG). PEG is a polymer incorporated in numerous pharmaceutical products because of its favorable, inert properties. The results of allergy testing in adults to date indicate that IgE mediated anaphylaxis to PEG allergy is rarely identified after COVID-19 mRNA vaccine reactions. Numerous individuals with presumed anaphylaxis have tolerated a second vaccine after evaluation and testing by an allergist, suggesting either misdiagnosis or a novel immune mechanism. Confirmed anaphylactic reactions to COVID-19 mRNA vaccines are rare, likely due to a lack of preexisting IgE against the vaccine components, including PEG.
Project description:Autoimmunity following COVID-19 vaccination has been reported. Herein, a 79-year-old man with clinical and immunological features of autoimmune hepatitis type 1 after ChAdOx1 nCoV-19 vaccination is presented. Clinical manifestations rapidly remitted after the instauration of immunomodulatory management. This case, together with a comprehensive review of the literature, illustrates the association between COVID-19 vaccines and the development of autoimmune conditions.
Project description:There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
Project description:BNT162b2 (Comirnaty®; BioNTech and Pfizer) is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine for the prevention of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. BNT162b2 encodes the SARS-CoV-2 spike protein, the expression of which elicits immune responses against the antigen in recipients. In early December 2020, BNT162b2 received a temporary emergency use authorization (EUA) in the UK and, subsequently, a series of approvals or authorizations for emergency use in Bahrain, Canada, Mexico, Saudi Arabia and the USA. Soon after, BNT162b2 received conditional marketing authorizations in Switzerland (19 December 2020) and the EU (21 December 2020) for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 16 years of age and older. BNT162b2 is administered intramuscularly in a two-dose regimen. This article summarizes the milestones in the development of BNT162b2 leading to these first approvals for the prevention of COVID-19.
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.