This study is being done to understand and measure how the immune system responds to and remembers different types of vaccines. To do this, four vaccines approved by the U.S. Food and Drug Administration (FDA) will be given simultaneously to participants. Participants will be volumteers who are healthy adults (18 years old or older) and willing to receive the yearly trivalent inactivated influenza vaccine (TIV), the tetanus, diphtheria, and acellular pertussis vaccine (Tdap), the nonvalent HPV (HPV) vaccine, hepatitis A virus (HAV) vaccine and undergo study procedures.

Procedures will include:

• medical history relevant to the study, including medications and vaccines received.
• Vitals (blood pressure, pulse) and temperature
• Height and weight.
• Physical exams.
• Receive the TIV, Tdap, HPV, and HAV vaccines.
• Blood samples collected for immunologic tests and genetic analysis.
• Donate bone marrow by needle aspiration at a maximum of seven visits.
• Complete memory aid every evening for 7 days after vaccination

Optional Procedures include:

• Donate bone marrow core biopsies at the same visits
• Ultrasound of lymph nodes and fine needle aspirates of lymph nodes in both arm pits at a maximum of eight separate visits

There will be a screening visit and and a Day 1 where vaccinations will occur and subsequent visits at Day 8, Day 14, Day 29, Day 57, Day 121, Day 181, Day 366, Day 546, and Day 731.

At each of these visits health status, vital signs and blood collection will occur.

A bone marrow aspirate and lymph node aspirate will be collected at screening.

The six additional bone marrow aspirates will be repeated at D29, D91, D181, D366, D546, and D731. The optional bone marrow core biopsy will also be repeated at that time.

Up to seven separate visits will be scheduled for the follow-up lymph node aspirates (D29, D57, D91, D181, D366, D546, and D731)

Study participation will be 24 months.

Inclusion Criteria:

1. Healthy participants over 18 years of age.
2. Able to understand and give informed consent.
3. Willing to receive TIV, Tdap, HPV, and HAV vaccinations
4. In stable health, as determined by medical history and targeted physical exam related to this history.
5. Willing to give BMA samples
6. For those willing to give FNA or BMCB samples, Willing to:

give FNA specimens OR give BMCB specimens OR give both FNA and BMCB specimens

Exclusion Criteria:

1. Has a history of severe allergic reaction to any component of the TIV, Tdap, HPV, or HAV vaccines, including allergic reactions to neomycin, yeast or prior severe reaction after vaccination including anaphylaxis or encephalopathy within 7 days of vaccination.
2. Has a current or previous diagnosis of immunocompromising condition to include human immunodeficiency virus, immune-mediated disease requiring immunosuppressive treatment, or other immunosuppressive condition.
3. Has received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 6 months prior to Screening (for corticosteroids ≥ 10 mg/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.
4. Is acutely ill or febrile (temperature >38.0 C [100.4F] less than 72 hours prior to or at the day 1 visit. Participants who meet this criteria may be rescheduled.
5. Currently has symptomatic acute or unstable chronic disease requiring medical or surgical care, to include significant change in therapy or hospitalization, at the discretion of the investigator.
6. History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions or occupational conditions that in the opinion of the investigator would preclude compliance with the study.
7. Has received any vaccine ≤ 28 days prior to the injection (Day 1) or plans to receive a vaccine within 28 days before or after the study injection. These participants may be rescheduled.
8. Has received the 2025-2026 influenza trivalent, inactivated vaccine or quadrivalent, inactivated vaccine.
9. Has received any quadrivalent or trivalent inactivated influenza, Tdap, HPV, or HAV vaccines ≤ 180 days prior to the injection (Day 1).
10. Pregnant women and nursing mothers or women who are planning to become pregnant for the study duration.
11. Have donated blood, blood products or bone marrow within 30 days before study vaccination, plan to donate blood at any time during the duration of participant study participation, or plan to donate blood within 30 days after the last blood draw.
12. Any condition in the opinion of the investigator that would interfere with the proper conduct of the trial.
13. Coagulopathy (primary or iatrogenic) which would contraindicate bone marrow aspirate or core biopsy for participants willing to have those procedures done

The data to be generated and shared from this proposal will include clinical data with low-risk for identification, clinical from patients from human cohorts (described in more detail in the proposal) and a wealth of immunological data generated from assays performed on the clinical specimens derived from these subjects. The types of data to be uploaded include mainly .xls(x) or fasta files but also potentially .pdf, .doc(x), and .txt files

Data will be deposited in the ImmPort, NCBI (GenBank, SRA, and dbGaP), MassIVE, PDB or EMDB data repositories. Each study deposited in ImmPort, PDB, and EMBD will be assigned a permanent digital object identifier (DOI) that will be cited in each publication. Each study or sequence(s) deposited in GenBank, SRA, or dbGaP will be assigned a permanent accession number that also will be cited in each publication. These persistent unique identifiers are searchable on Google and/or Pubmed. Each proteomic study deposited in MassIVE will be assigned a permanent ProteomeXchange accession that will be cited in each publication and is searchable on the MassIVE website. All of the data repositories to be used require rich metadata to be submitted along with each dataset to ensure that data is easy to find, access, and identify.

Data deposited on GenBank, SRA, MassIVE, PDB or EMDB will not be controlled and will be accessible for free download by the wider community. For data in ImmPort, users will need to register and agree to a Data Use Agreement prior to free download. Summaries of studies and the contents of measured variables deposited on dbGaP will be made public, while access to individual-level data will require authorization.