Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults

Inclusion Criteria: General and Demographic Criteria: * Age of 18 to 50 years * Weight less than or equal to 115 kg * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to enrollment with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last study visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: * Willingness to receive HIV test results * Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling * Assessed by the clinic staff as being at "low risk" for HIV infection \[low risk guidelines are found on the protocol home page on the HVTN Members' site (https://members.hvtn.org/protocols/hvtn116)\] and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit Laboratory Inclusion Values: Hemogram/CBC * Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male * White blood cell count equal to 2,500 to 12,000 cells/mm\^3 * Total lymphocyte count greater than or equal to 800 cells/mm\^3 * Remaining differential either within institutional normal range or with site physician approval * Platelets equal to 125,000 to 550,000/mm\^3 Chemistry * Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase less than 1.25 times the institutional upper limit of normal; creatinine less than or equal to institutional upper limit of normal Virology * Negative HIV-1 and -2 blood test: U.S. volunteers must have a negative Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA). Non-U.S. sites may use locally available assays that have been approved by HVTN Laboratory Operations. * Negative hepatitis B surface antigen (HBsAg) * Negative anti-hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive Urine * Normal urine: * Negative urine glucose, and * Negative or trace urine protein, and * Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range) Reproductive Status: * Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to initial biopsy for groups 1-3 and prior to initial infusion for groups 4-5 on the day of enrollment. Persons who are NOT of reproductive potential due to having undergone bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. Reproductive Status: United States: A volunteer who was born female must: * Agree to consistently use effective contraception (see the protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods: * Condoms (male or female) with or without a spermicide, * Diaphragm or cervical cap with spermicide, * Intrauterine device (IUD), * Hormonal contraception, or * Any other contraceptive method approved by the HVTN 116 Protocol Safety Review Team (PSRT) * Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has \[1\] documentation of azoospermia by microscopy, or \[2\] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy); * Or not be of reproductive potential, such as having had a bilateral oophorectomy, or tubal ligation; * Or be sexually abstinent. South Africa: A volunteer who was born female must: * Agree to consistently use effective contraception (see the protocol for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception for participants in South Africa is defined as using 2 methods of birth control. ONE barrier contraceptive method: * Condoms (male or female) * Diaphragm or cervical cap PLUS ONE of the following methods: * Intrauterine device (IUD), * Hormonal contraception, or * Successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has \[1\] documentation of azoospermia by microscopy, or \[2\] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy), or * Any other contraceptive method approved by the HVTN 116 PSRT Or not be of reproductive potential, such as having had a bilateral oophorectomy, or tubal ligation; Or be sexually abstinent. * Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit Mucosal Specimen Collection * Volunteers 21 years of age and older who were born female: Pap smear (verified by medical records) is required within: * the 3 years prior to enrollment with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance), OR * the 5 years prior to enrollment, with the latest result reported as normal, or ASCUS with no evidence of high risk HPV. * If no Pap smear was done within the last 3 years (or within the last 5 years, if high risk HPV testing was performed), the volunteer must be willing to undergo a Pap smear with the result reported (verified by medical records) as normal or ASCUS prior to sample collection. * Willing to have mucosal secretions and tissue biopsies collected * Willing to abstain from sexual intercourse for the required period after each biopsy collection Exclusion Criteria: General * Blood products received within 120 days before first infusion, unless eligibility for earlier enrollment is determined by the HVTN 116 PSRT * Investigational research agents received within 30 days before first infusion * 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 116 study * Pregnant or breastfeeding * Active duty U.S. military personnel with the potential of being deployed during the study 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 116 PSRT will determine eligibility on a case-by-case basis. * Non-HIV experimental vaccine(s) received within the last 6 months in a prior vaccine trial. Exceptions may be made for some vaccines and vaccine trials. For volunteers who have received an experimental vaccine(s) less than 6 months ago, eligibility for enrollment will be determined by the HVTN 116 PSRT on a case-by-case basis. * Live attenuated vaccines other than influenza vaccine received within 10 days before first infusion or scheduled within 10 days after first infusion (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever) * Previous receipt of humanized or human mAbs whether licensed or investigational Immune System * Immunosuppressive medications received within 30 days before first infusion. (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; or \[3\] topical corticosteroids for mild, uncomplicated dermatitis) * Serious adverse reactions to VRC01 and VRC01LS formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain * Autoimmune disease (Not exclusionary: mild, well-controlled psoriasis) * Immunodeficiency Clinically Significant Medical Conditions * Untreated or incompletely treated syphilis infection * 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 infusions or blood draws, including perceived inability to establish venous access * A condition that requires regular use of any anticoagulant medications (not including aspirin or NSAIDs), * 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 study product, or * Any condition specifically listed among the exclusion criteria below. * 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, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.) * Thyroidectomy, or thyroid disease unless well controlled (normal T3/T4/TSH) with medication * 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 as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 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 greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment. * Bleeding disorder diagnosed by a doctor (e.g., 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 hereditary angioedema, acquired angioedema, or idiopathic angioedema * For those undergoing rectal biopsies, a rectal condition, such as an active infection or inflammation of the colorectal area (e.g., an HSV-2 outbreak or inflamed hemorrhoids or colitis/diarrhea), internal hemorrhoids, or any other condition noted during screening rectal exam via anoscope or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling * For those undergoing vaginal and cervical biopsies, any condition noted during pelvic exam via speculum or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling * An active genital tract condition, such as an active infection or inflammation of the genital tract (e.g., genital sores or ulcers, penile or abnormal vaginal discharge, genital warts that are symptomatic or requiring treatment) or any other condition that in the opinion of the clinician represents a contraindication to mucosal sampling * Hysterectomy * Menopause