High-Resolution Single Cell Profiling of SARS-CoV-2 Vaccine Responsiveness in Healthy Adults

mRNA vaccines, administered in two doses, have been highly effective against SARS-CoV-2 and are now being explored for broader applications. However, how human immune cells respond to these platforms, particularly differences between primary and booster responses, remains incompletely understood. Here, we longitudinally profiled plasma and peripheral blood mononuclear cells from individuals without prior infection or vaccination receiving BNT162b2 (Pfizer, n=22), mRNA-1273 (Moderna, n=6), or the adenoviral vector vaccine Ad26.COV2.S (J&J, n=3). Using DOGMA-seq, a single-cell assay integrating transcriptomic and epigenomic profiling, we show that while the most robust responses occurred after the second dose, the first mRNA dose induces a unique interferon state in a subset of monocytes and dendritic cells.]]>
SAMPLE COLLECTION TIMEPOINTInclusion Criteria Able and willing to provide written informed consent Male or Female, aged ≥21 years Weight ≥ 110 pounds Scheduled to receive FDA Emergency Use Authorized (EUA) SARS-CoV-2 vaccine as part of the Federal SARS-CoV-2 Vaccination Program (Pfizer, Moderna or J&J vaccine). Available to attend all study visits around their SARS-CoV-2 vaccination over a one-year period Willing to undergo blood draws at each of the study visits Willing to agree to genomic testing of samples and sharing of de-identified genomic data generated from samples at the conclusion of the research Exclusion Criteria History of laboratory-confirmed (by PCR) COVID-19 infection Has already received a SARS-CoV-2 vaccine Blood donation during the period of study participation Participation in a COVID-19 treatment or prophylactic drug trial prior to and for the duration of the study Recent acute infection within three weeks prior to enrollment Known history of any of the following co-morbid conditions: Cancer requiring surgical or medical cancer treatment in the past 6 months (with the exception of skin cancer excision) Congestive Heart Failure Ischemic Heart Disease Myocarditis Congenital abnormalities (PI to evaluate) Uncontrolled diabetes mellitus Renal failure Chronic obstructive pulmonary disease or severe asthma Severe autoimmune disease requiring biological therapy Use of medicines during past 6 months known to alter immune response such as high-dose corticosteroids (≥ 10 mg/day of prednisone or equivalent) HIV, AIDS or other Immunodeficiency Recent (≤ 3 months) severe trauma or major surgery (PI to evaluate) Current substance and/or alcohol abuse Pregnant or nursing (for women of childbearing potential) Patients currently residing in the Department of Correction Inability to comply with the protocol requirements Any other condition that, in the opinion of the PI, might interfere with study objectives Post-vaccine Exclusion Criteria (Day 0) Received the Pfizer COVID-19 Vaccine and scheduled Dose 2 for <21 or >25 days from Dose 1 Received the Moderna COVID-19 Vaccine and scheduled Dose 2 for <26 or >32 days from Dose 1 Experienced severe allergic reactions after the first dose of the COVID-19 vaccine requiring hospitalization or epinephrine ]]>