Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults

General

Blood products received within 120 days before first vaccination

Investigational research agents received within 30 days before first vaccination

Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia

Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 137 study

Pregnant or breastfeeding

Active duty and reserve US military personnel

Vaccines and other Injections

HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 137 PSRT will determine eligibility on a case-by-case basis.

Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 137 PSRT will determine eligibility on a case-by-case basis

Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 137 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 137 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 year ago, eligibility for enrollment will be determined by the HVTN 137 PSRT on a case-by-case basis.

Live attenuated vaccines received within 30 days before first vaccination or scheduled within 30 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; live attenuated influenza vaccine)

Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination or scheduled for 14 days after injection (eg, tetanus, pneumococcal, hepatitis virus A or B)

Previous receipt of HEPLISAV, Shingrix, or RTS,S/AS01B/Mosquirix vaccine received within 30 days prior to first vaccination or scheduled for 30 days after injection.

Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

Immune System

Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatologic condition; or \[4\] a single course of oral/parenteral prednisone or equivalent at doses ≤ 60 mg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment)

Serious adverse reactions to vaccines or to vaccine components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child.)

Immunoglobulin received within 60 days before first vaccination (for mAb see criterion above)

Autoimmune disease, current or history

AESIs: Volunteers who currently have, or have a history of, any condition that could be considered an AESI for the product(s) administered in this protocol (representative examples are listed in the study protocol)

Immunodeficiency

Clinically significant medical conditions

Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

* A process that would affect the immune response,

* A process that would require medication that affects the immune response,

* Any contraindication to repeated injections or blood draws,

* A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,

* A condition or process for which signs or symptoms could be confused with reactions to vaccine, or

Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent

Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

Current anti-tuberculosis (TB) prophylaxis or therapy

Asthma other than mild, well-controlled asthma (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:

* Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

* Uses moderate/high dose inhaled corticosteroids, or

* In the past year has either of the following:

* Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;

* Needed emergency care, urgent care, hospitalization, or intubation for asthma

Diabetes mellitus type 1 or type 2 (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes.)

Thyroidectomy, or thyroid disease requiring medication during the last 12 months

Hypertension:

* If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently \< 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.

* If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.

Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)

Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)

Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.

Asplenia: any condition resulting in the absence of a functional spleen

History of generalized urticaria, angioedema, or anaphylaxis. (Not exclusionary: angioedema or anaphylaxis to a known trigger with at least 5 years since last reaction to demonstrate satisfactory avoidance of trigger.)

What this study is about