A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses

Inclusion Criteria: 1. Individuals 40 - 64 years of age 2. Received at least two doses of a COVID-19 mRNA vaccine (Moderna or Pfizer) \> 120 days before study entry 3. Nasal SARS-CoV-2 negative by molecular (polymerase chain reaction, PCR) testing at screening 4. The following laboratory criteria must be met at screening: 1. Total white blood cell (WBC) count \> 3500 cells/mm3 2. Absolute neutrophil count (ANC) \> 1500 cells/mm3 3. Hemoglobin \> 13.5 g/dL if male sex and \> 12.0 g/dL if female sex 4. Platelet count \> 140,000/uL 5. Estimated creatinine clearance (CrCl) \> 50 mL/min by Cockroft-Gault equation 6. Total bilirubin ≤ 1.1x upper limit of normal (ULN) 7. Aspartate aminotransferase (AST) ≤ 1.3x ULN 8. Alanine aminotransferase (ALT) ≤ 1.3x ULN 5. Individuals of reproductive potential must have a negative serum or urine beta-human chorionic gonadotropin (ß-HCG) test at screening and within 48 hours prior to entry. Reproductive potential is defined as: * Participants who have reached menarche * Participants who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available * Participants who have not undergone surgical contraception (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy) NOTE: Participants who have undergone bilateral tubal ligation within the 24 weeks prior to screening are considered to be of reproductive potential and, if participating in sexual activity that could lead to pregnancy, contraception is required as per 5.2.2 exclusion criterion 2. 6. Able and willing to provide informed consent Exclusion Criteria: Participants are excluded from the study if any of the following criteria are met: 1. Pregnant or breastfeeding 2. For participants capable of becoming pregnant and engaging in sexual activity that can lead to pregnancy, unwillingness to use contraception during participation in the study. For participants capable of becoming pregnant, two of the following forms of contraception are required through 30 days following administration of study intervention, one of which must be a barrier method: 1. Condoms (male or female) with or without a spermicidal agent 2. Diaphragm or cervical cap with spermicide 3. Intrauterine device (IUD) 4. Hormone-based contraceptive such as oral birth control pills 3. Known close contact with anyone with confirmed SARS-CoV-2 infection (defined as positive SARS-CoV-2 nucleic acid or antigen testing by laboratory-based or home self-test) within 2 weeks prior to expected study entry 4. Plan to receive a non-study SARS-CoV-2 vaccine within 8 weeks after study entry 5. HIV infection 6. Hepatitis B core antibody or hepatitis B surface antigen positive at screening 7. Current active hepatitis C. Participants must be hepatitis C virus (HCV) antibody negative or have evidence of cleared HCV infection. If the participant is HCV antibody positive or indeterminate, an unquantifiable HCV RNA result (below lower limit of quantification, either target detected or target not detected) within 42 days prior to study entry is required. Those who are currently receiving HCV antiviral therapy or those who have received HCV treatment in the last 3 months prior to study entry will be excluded. 8. History of cirrhotic liver disease 9. History of thrombosis with thrombocytopenia syndrome (TTS), immune thrombocytopenia, thromboembolic events, capillary leak syndrome, other thrombotic disease or known increased risk of thrombosis due to genetic disorders or malignancy 10. History of or active autoimmune disease that has required systemic immunosuppressive or immunomodulatory therapy 11. History of myocarditis, pericarditis, or myopericarditis 12. Potential myocarditis or pericarditis identified at screening, defined as high-sensitivity troponin I (hsTnI) \> ULN or 12-lead ECG compatible with pericarditis WITH compatible symptoms (regardless of troponin I level) at screening 13. History of Guillain-Barré syndrome 14. History of coagulopathy or bleeding disorder considered a contraindication to intramuscular injection or phlebotomy 15. Symptomatic acute or chronic illness requiring ongoing medical or surgical care, including requirement for new medications, in the past 3 months. Transient illnesses or injuries that are resolved prior to screening are not exclusionary. Minor adjustments in stable therapy for chronic conditions such as hypertension are not exclusionary. Use of over-the-counter medications for any acute or chronic illness is also not exclusionary. 16. Serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with the ability to adhere to study requirements or to give informed consent 17. Treatment with systemic immunosuppressive or immunomodulatory drugs, and/or exposure to any immunosuppressive/immunomodulatory drug in the 30 days prior to study entry (e.g. corticosteroid therapy equal to or exceeding a dose of 20 mg/day of prednisone for more than 10 days, interleukins, interferons, methotrexate, rituximab, and cancer chemotherapy). Use of topical, inhaled, intra-articular, or nasal steroid use is not exclusionary. 18. Active malignancy or history of malignancy within the 4 years prior to study entry. Non-melanoma skin cancers (such as basal or squamous cell skin cancers) and non-invasive cervical or anal intraepithelial lesions are not exclusionary. 19. History of solid organ or hematopoietic stem cell transplantation 20. History of primary immunodeficiency disorder 21. Ongoing complications or morbidity associated with prior diagnoses of malignancies requiring continued medical or surgical intervention. Chronic stable complications or morbidity not requiring new medications or other medical or surgical intervention in the past 3 months are not exclusionary. 22. Administration or planned administr