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1.
Nat Immunol ; 23(4): 543-555, 2022 04.
Article in English | MEDLINE | ID: covidwho-1738613

ABSTRACT

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.


Subject(s)
CD8-Positive T-Lymphocytes , Vaccines , Adaptive Immunity , Animals , BNT162 Vaccine , Humans , Immunity, Innate , Mice , Vaccines, Synthetic , mRNA Vaccines
2.
Am J Pharm Educ ; 86(6): 8661, 2022 08.
Article in English | MEDLINE | ID: covidwho-1485395

ABSTRACT

When COVID-19 shuttered schools across the nation, it propelled higher education institutions into uncharted territories. Institutions had to make rapid decisions in a short period of time with limited information or direction. In these uncertain and challenging times, pharmacy academics in the United States and around the world reached out to one another to discuss, share, and learn. What began with a few members of the Student Services Personnel Special Interest Group (SIG) grew to many members who banded together as a team through open discussions to innovative problem-solving. Working together through open discussions created a setting that promoted diverse ideas, multiple perspectives, and a depth of knowledge to address some of the most challenging issues faced by pharmacy education. When partnering together, institutions had a much greater resource of knowledge and support that could be leveraged to broadly benefit the Academy.


Subject(s)
COVID-19 , Education, Pharmacy , Pharmaceutical Services , Pharmacy , COVID-19/epidemiology , Humans , United States , Universities
3.
JAMA Netw Open ; 4(9): e2125524, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1414844

ABSTRACT

Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported. Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines. Design, Setting, and Participants: This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing. Exposures: FDA-authorized mRNA COVID-19 vaccines. Main Outcomes and Measures: Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms. Results: Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine. Conclusions and Relevance: Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.


Subject(s)
COVID-19 Vaccines/adverse effects , Hypersensitivity/diagnosis , Adolescent , Adult , Aged , COVID-19 Vaccines/therapeutic use , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Hypersensitivity/epidemiology , Male , Middle Aged , Risk Factors , United States/epidemiology , United States Food and Drug Administration/organization & administration , United States Food and Drug Administration/statistics & numerical data , Vaccination/adverse effects
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