Safety, Tolerability, and Immunogenicity of ALFQ in a HIV Vaccine Containing A244 and B.65321 in Healthy Adults

Inclusion Criteria:

1. Healthy adults between the ages 18-55 years (inclusive)
2. Must be at low risk for HIV infection per investigator assessment and using the studyrisk assessment tool.
3. Able and willing to provide written, informed consent
4. Able and willing to comply with all research requirements, in the opinion of theInvestigator
5. Agreement to refrain from blood donation during the course of the study
6. Minimum body weight of 110 pounds (lbs) (50kg)
7. Laboratory Criteria within 30 days before enrollment:
8. Hemoglobin ≥ 12.0 g/dL for women; ≥ 12.5 g/dL for men
9. White Blood Cell count = 3,500-10,800 cells/mm3
10. Platelets ≥140,000/mm3 and ≤ 450,000/mm3
11. Alanine aminotransferase (ALT; SGPT) <1.25 x Upper Limit of Normal (ULN)
12. Serum creatinine ≤ 1.25 x institutional upper limit of the reference range
13. Negative HIV testing (HIV Ab / antigen 4th generation screen with reflexconfirmatory RNA testing)
14. Negative HBsAg and hepatitis C antibody testing Note: As above, Grade 1 lababnormalities detected on screening may be repeated at PI discretion. PersistentGrade 1 abnormalities that are felt to represent the non-pathologic baseline forthe subject will be documented before a subject is enrolled in the trial and areallowable per discretion of the PI.
15. Birth control requirements: All participants assigned female at birth must meet one of the following 2 criteria:
16. No reproductive potential due to post-menopausal status (12 months of natural [spontaneous] amenorrhea) or hysterectomy, bilateral oophorectomy, or tuballigation
17. People of childbearing potential should agree to practice highly effectivecontraception at least 30 days before enrollment and through 3 months post-lastvaccination, using one of the following methods: condoms (male or female) withspermicide; diaphragm, or cervical cap with spermicide; intrauterine device;contraceptive pills, patch, injection, intravaginal ring or other FDA-approvedcontraceptive method; male partner has previously undergone a vasectomy;abstinence
18. All participants are encouraged to engage in safe sex practices to prevent HIVacquisition
19. For all participants assigned female at birth, except those with a history ofhysterectomy or bilateral oophorectomy, a negative β-human chorionic gonadotropin (HCG) pregnancy test (urine) on the day of enrollment and each vaccination day isrequired. Because tubal ligations have a failure rate that is not insignificant, andbecause 12 months of spontaneous amenorrhea can be a result of polycystic ovariansyndrome and does not completely preclude pregnancy, a negative β- HCG pregnancy testat enrollment and on each vaccination day is also required for participants assignedfemale at birth with a history of either of these).
20. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia)that would prevent compliance with planned study visits
21. Test of Understanding (TOU) (minimum passing score of 80% with 2 attempts permitted)

Exclusion Criteria:

1. Receipt of any investigational HIV vaccine or investigational adjuvant
2. Received an investigational product in the 30 days before enrollment, or planned toreceive during the study period. This does not include products with emergency useauthorization.
3. Concurrent participation in another clinical research study
4. Any serious medical illness or condition
5. Receipt of immunoglobulins or blood products within 3 months before enrollment
6. Any history of anaphylaxis or allergy to study product
7. History of sickle cell trait or disease
8. Pregnancy, lactation, or intention to become pregnant during the study
9. History of active/recent cancer still within treatment or active surveillancefollow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ).Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable atPrincipal Investigator (PI) discretion.
10. History of autoimmune disease
11. History of Potentially Immune-Mediated Medical Conditions (PIMMCs)
12. Suspected or known current alcohol or drug abuse as defined by an alcohol intake ofgreater than 3 drinks a day on average for a man, and greater than 2 drinks a day onaverage for a woman
13. Any other significant disease, disorder or finding which may significantly increasethe risk to the volunteer because of participation in the study, affect the ability ofthe volunteer to give informed consent, participate in the study, or impairinterpretation of the study data, in the opinion of the Investigator
14. History of splenectomy
15. History of confirmed or suspected immunodeficiency
16. History of hereditary angioedema (HAE) acquired angioedema (AAE), or idiopathic formsof angioedema
17. History of asthma that is unstable or required emergent care, urgent care,hospitalization, or intubation during the past 2 years
18. History of diabetes mellitus (type I or II), with the exception of gestationaldiabetes
19. History of thyroid disease (except for well controlled hypothyroidism)
20. History of idiopathic urticaria within the past year
21. History of hypertension that is not well controlled by medication or that ispersistently greater than 140/95 at screening
22. History of bleeding disorder diagnosed by a doctor (e.g., factor deficiency,coagulopathy, or platelet disorder requiring special precautions) or significantbruising or bleeding difficulties with IM injections or blood draws
23. History of chronic or active neurologic disease to include seizure disorder andchronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii)seizures secondary to alcohol withdrawal more than 3 years ago
24. Subjects receiving any of the following substances:
25. Systemic immunosuppressive medications or cytotoxic medications within 12 weeksbefore enrollment [with the exception of a short course of corticosteroids (≤ 14days duration or a single injection) for a self-limited condition at least 2weeks before enrollment; inhaled, intranasal or topical steroids are notconsidered exclusionary
26. Treatment with known immunomodulators including allergy immunotherapy (other thannonsteroidal anti-inflammatory drugs [NSAIDs] or stable maintenance immunotherapy (doses not in the process of being increased), at the discretion of the ProtocolSafety Review Team (PSRT)) for any reason
27. Live attenuated vaccines within 30 days before initial study vaccineadministration
28. Medically indicated subunit, messenger ribonucleic acid (mRNA), or killedvaccines, e.g., influenza, pneumococcal, vaccines with Quillaja saponaria-21 (QS-21) as an adjuvant, or allergy treatment with antigen injections, planned foradministration 14 days before or after study vaccine administration
29. History of arthritis diagnosis other than osteoarthritis
30. History of other diagnosed rheumatoid disorders
31. Has an acute illness or temperature ≥38.0 degrees Celsius (C)/100.4 degrees Fahrenheit (F) on any study injection day or within 48 hours of planned study injection. Note: Participants will not be excluded from further consideration for enrollment and studyinjections. Volunteers with fever or an acute illness on the day of study injection or inthe 2 days before the study injection may be re-assessed by a study physician forresolution of the condition and enrolled and receive the study injection so long as theinjection is within allowable windows. Military personnel will be excluded fromparticipation in this study, regardless of leave status due to the potential for afalse-positive HIV test result on mandatory HIV testing. This could have adverse effects ondeployment status. Final evaluation of eligibility will be based on the medical judgment of the investigatorbased on his/her medical and research experience.