A Study to Evaluate the Safety and Immunogenicity of a Single Dose of H1ssF-3928 mRNA-LNP in Healthy Adults

Inclusion Criteria:

1. Provide written informed consent prior to initiation of any study procedure.

2. Are able to understand and comply with planned study procedures and be available forall study visits.

3. Are males or non-pregnant, non-breastfeeding females, 18 to 49 years of age,inclusive at time of screening and enrollment.

4. Must agree to collection of venous blood and nasal absorption specimens per protocoland enrollment in DMID Protocol No. 19-0025 biorepository protocol for secondaryresearch and use of residual biologic specimens.

5. Are in good health* and do not have clinically significant medical, psychiatric,chronic or intermittent health conditions including those listed in ExclusionCriteria (Section 1).

*As determined by medical history, medication use, and physical examination toevaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined asthose that have been present for at least 90 days, which would not affect theassessment of the safety of subjects or the immunogenicity of study vaccinations.These medical diagnoses or conditions should be stable for the last 60 days (nohospitalizations, emergency room [ER] or urgent care for condition [excludingmusculoskeletal conditions], or invasive medical procedure and no adverse symptomsthat need medical intervention such as medication change/supplemental oxygen). Thisincludes no change in chronic prescription medication, dose or in the 60 days priorto enrollment. Any prescription change that is due to change of health careprovider, insurance company, etc., or that is done for financial reasons, as long asin the same class of medication, will not be considered a deviation of thisinclusion criterion. Subjects may be on chronic or as needed (prn) medications if,in the opinion of the site PI or appropriate sub-investigator, they pose noadditional risk to subject safety or assessment of reactogenicity and immunogenicityand do not indicate a worsening or treatment of continued symptoms of medicaldiagnosis or condition. Note: Low dose topical, corticosteroids as outlined in theSubject Exclusion Criteria (see Section 1) as well as herbals, vitamins andsupplements are permitted.

6. Does not have an ongoing symptomatic condition* for which subject has had or hasongoing medical investigations but has not yet received a diagnosis or treatmentplan.

*e.g., ongoing fatigue without a diagnosis for symptom.

7. Pulse is 50 to 100 beats per minute, inclusive.

8. Systolic blood pressure is 90 to 140 mmHg, inclusive.

9. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

10. Body mass index (BMI) of 18 kilograms/square meter (kg/m^2) (inclusive) to <35kg/m^2 at screening

11. Women of childbearing potential* must agree to use or have practiced trueabstinence** or use at least 1 acceptable primary form of contraception.***

*Not of child bearing potential - post-menopausal females (defined as having ahistory of amenorrhea for at least one year) or a documented status as beingsurgically sterile (hysterectomy, bilateral oophorectomy, salpingectomy, or Essureplacement with history of documented radiological confirmation test at least 90 daysafter the procedure).

**True abstinence is 100% of time no sexual intercourse (male's penis enters thefemale's vagina). (Periodic abstinence [e.g. calendar, ovulation, symptothermal,post-ovulation methods] and withdrawal are not acceptable methods of contraception).

• Acceptable forms of primary contraception include monogamous relationship witha vasectomized partner who has been vasectomized for 180 days or more prior tothe subject receiving the study product, tubal ligation, intrauterine devices,birth control pills, and injectable/implantable/insertable hormonal birthcontrol products.

• Must use at least one acceptable primary form of contraception or trueabstinence for at least 30 days prior to receipt of study product and at leastone acceptable primary form of contraception or true abstinence for at least 30days following receipt of study product.

12. Women of childbearing potential must have a negative serum HCG pregnancy test atscreening and a negative urine HCG pregnancy test within 24 hours prior to the studyvaccination.

13. Male participants receiving VRC H1ssF_3928 mRNA-LNP must agree to refrain fromdonating sperm and to use contraception until Day 60 after vaccination.*

• Acceptable contraception includes abstinence from intercourse with a female ofchildbearing potential or use of a male condom when engaging in any activitythat allows for passage of ejaculate to a female during the intervention periodfor at least 60 days after study vaccination.

• Males in the immunogenicity comparator group do not have to refrain from spermdonation or abstain from intercourse or agree to use a male condom for purposesof this study.

14. Must have received at least one licensed seasonal influenza vaccine within theprevious 5 seasons.

Exclusion Criteria:

1. Have an acute illness* or fever (body temperature > / = 38.0 degrees Celsius/100.4degrees Fahrenheit), as determined by the site Principal Investigator (PI) orappropriate sub-investigator, within 72 hours prior to study vaccination.

*An acute illness which is nearly resolved with only minor residual symptomsremaining is allowable if, in the opinion of the site PI or appropriatesub-investigator, the residual symptoms will not interfere with the ability toassess safety parameters as required by the protocol.

2. Have any medical disease or condition that, in the opinion of the site PI orappropriate sub-investigator, is a contraindication to study participation.*

• Including acute, subacute, intermittent or chronic medical disease or conditionthat would place the subject at an unacceptable risk of injury, render the subjectunable to meet the requirements of the protocol, or may interfere with theevaluation of responses or the subject's successful completion of this trial.

3. Has a screening laboratory* > Grade 1.

*White blood cell count, absolute neutrophil count, absolute lymphocyte count,hemoglobin, platelet count, prothrombin time (PT), activated partial thromboplastintime (APTT), fibrinogen, creatinine, alanine aminotransferase (ALT), aspartateaminotransferase (AST), alkaline phosphatase, total bilirubin, lipase.

4. Has a positive urine toxicology screen (i.e., non-prescribed amphetamines, cocaine,and opiates).

5. Electrocardiogram (ECG) is deemed to be clinically significant by the PI orappropriate sub-investigator.

6. Total iron binding capacity, iron, ferritin and troponin (hsTnl) outside thelaboratory normal range at screening.

7. Have any known or suspected immunosuppressive condition, acquired or congenital, orautoimmune conditions as determined by history and/or physical examination.

8. Have immunosuppression as result of treatment including a recent history (within 6months prior to administration of study vaccine) or use of immunosuppressive orother immune-modifying drugs.

9. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years priorto study vaccination.

10. Have known active or recently active (12 months) neoplastic disease or a history ofany hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.

11. Have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infectionat screening.

12. Have a positive test result for hepatitis B surface antigen, hepatitis C virusantibody, or HIV types 1 or 2 antibodies at screening.

13. Have known chronic liver disease, including fatty liver disease.

14. Have a known allergy or severe allergic reaction to any components of the studyvaccine (including polyethylene glycol [PEG]) or the seasonal influenza vaccine (including egg protein).

15. Have a history of a severe reaction following previous immunization with aninvestigational, authorized, or approved influenza vaccine or mRNA or LNP-containingvaccine containing vaccine.

16. Have a history of Guillain-Barré Syndrome.

17. Have a known history of myocarditis or pericarditis.

18. Have a history of alcohol or drug abuse within 3 years prior to study vaccination.

19. Have any diagnosis, current or past, of schizophrenia, bipolar disease or otherpsychiatric diagnosis that may interfere* with subject compliance or safetyevaluations.

*As determined by the site PI or appropriate sub-investigator.

20. Have been hospitalized for psychiatric illness, history of suicide attempt, orconfinement for danger to self or others within 5 years prior to study vaccination.

21. Have taken oral or parenteral (including intra-articular) corticosteroids of anydose within 30 days prior to study vaccination. Intranasal or topical (skin or eyes)corticosteroids are permitted.

22. Have taken high-dose inhaled or nebulized corticosteroids* within 30 days prior tostudy vaccination.

*High-dose defined as per age as using inhaled high-dose per reference chart in theNational Heart, Lung and Blood Institute Guidelines for the Diagnosis and Managementof Asthma (EPR-3) or other lists published in UPTODATE

23. Have any significant disorder of coagulation requiring ongoing or intermittenttreatment.

24. Have received seasonal influenza vaccine within 90 days prior to enrollment or plansto receive a seasonal influenza vaccine 60 days after study vaccination.

25. Have received any approved or authorized vaccines other than seasonal influenzavaccine within 60 days before enrollment or plans to receive an approved orauthorized vaccine 60 days after study vaccination.

26. Have a known history of documented influenza infection within the past 90 days.

27. Have a history of receipt of an investigational H1 influenza vaccine within the past 10 years.

28. Have a history of receipt of a ferritin-based vaccine or an investigational H5influenza vaccine.

29. Previous participation in DMID Protocol No. 18-0010 human influenza challenge study.

30. Received immunoglobulin and/or any blood products (except Rho D immunoglobulin)within the 90 days prior to study vaccination.

31. Received an experimental agent within 60 days prior to the study vaccination orexpect to receive another experimental agent during the trial-reporting period.*

*Including vaccine, drug, biologic, device, blood product, or medication.

**Other than from participation in this trial

32. Are participating or plan to participate in another clinical trial with aninterventional agent* that will be received during the trial-reporting period.*

• Including licensed or unlicensed vaccine, drug, biologic, device, bloodproduct, or medication.

• Approximately 12 months after the first study vaccination.

33. The subject has any abnormality or permanent body art (e.g., tattoo) that, in theopinion of the investigator or appropriate sub-investigator, would obstruct theability to observe local reactions at the injection site.

34. Donation of blood or blood products within 30 days prior to dosing and plans todonate within 60 days following dosing.

35. Has had significant exposure to someone with laboratory-confirmed severe acuterespiratory syndrome (SARS-CoV-2) infection or influenza in the 14 days prior toscreening or during the period between screening and enrollment visit.*

*Defined by the Centers for Disease Control and Prevention (CDC) as a close contactwith someone who has COVID-19.

36. Has had a positive SARS-CoV-2 test (home or laboratory-based) within 14 days priorto the screening visit or during the period between screening and enrollment visits.