| 5.1 Inclusion criteria General and Demographic Criteria ● Age of 18 up to 40 years. ● Access to a participating CRS and willingness to be followed for the planned duration of the study. ● Ability and willingness to provide informed consent. ● Willing to consent to pharmacogenetic testing of samples ● Willingness to have sample collection using the leukapheresis procedure ● Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly. ● Willing to be contacted after completion of scheduled clinic visits for a total of 2 years following initial study injection. ● Agrees not to enrol in another study of an investigational product during participation in the trial. ● Agrees not to enrol into any other study (whether interventional or non–interventional), without informing the site principal investigator. Prior PSRT approval is required for any co-enrolment decisions. ● Good general health according to the clinical judgement of the site investigator. ● HIV-Related Criteria: o Willingness to receive HIV test results. o Willingness to discuss HIV infection risks and amenable to HIV risk reduction counselling. o Assessed by the clinic staff as being at “low risk” for HIV infection and committed to maintaining behaviour consistent with low risk of HIV exposure through the last required protocol clinic visit. Laboratory Inclusion Values 1. Full blood count (FBC): ● Haemoglobin o ≥ 11.0 g/dL for volunteers who were assigned female sex at birth o ≥ 13.0 g/dL for volunteers who were assigned male sex at birth ● White blood cell count ≥ 2,500 cells/mm3 with normal differential, or differential approved by Clinical trial site Principal Investigator (PI) as not clinically significant ● Total lymphocyte count ≥ 650 cells/mm3 with normal differential, or differential approved by the Principal Investigators as not clinically significant ● Remaining differential either within institutional normal range or with investigator approval. ● Platelets ≥ 125,000 cells/mm3. 2. Chemistry: ● Alanine aminotransferase (ALT) < 1.25 times the institutional upper limit of normal; ● Creatinine <1.1 times the institutional upper limit of normal. ● Serum Calcium level of > 8.5 mg/dL Virology ● Negative HIV-1 and HIV-2 blood test. ● Negative Hepatitis B surface antigen (HBsAg). ● Negative anti-Hepatitis C virus antibodies (anti-HCV) ● Normal urinalysis: Urine protein or haemoglobin negative If protein or blood/haemoglobin on urine dipstick, see Section 9.11. Reproductive Status ● Volunteers who were assigned female sex at birth: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test at screening (i.e., prior to randomization) and prior to study product administration on the day of study product administration. Persons who are NOT of reproductive potential due to having undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. ● Reproductive status: A volunteer who was assigned female sex at birth: Must agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrolment through to Visit 11. Effective contraception is defined as using the following methods: Intrauterine device (IUD), Hormonal contraception, Tubal ligation, or Any other contraceptive method approved by the PSRT Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, or bilateral oophorectomy (verified by medical records);or women having exclusively sex with women ● Volunteers who were assigned female sex at birth 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. |
5.2 Exclusion criteria General 1. Blood products received within 120 days before first vaccination. 2. Has donated ≥450 mL of blood products within 28 days prior to the enrolment visit or plans to donate blood products during or within 28 days post-study participation. 3. Investigational products received within 30 days before first vaccination. 4. Body mass index (BMI) ≤18 and ≥ 40 5. Previous or current recipient of an investigational product or any other study that requires HIV antibody testing during the planned duration of the study. 6. Pregnant or breastfeeding 7. Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study site staff, or sponsor personnel Vaccines and other Injections 1. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the PSRT will determine eligibility on a case-by-case basis. 2. Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be made by the PSRT on a case-by-case basis. 3. Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. 4. Live attenuated vaccines received within 30 days before first vaccination or scheduled within 28 days after injection (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine). 5. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, Hepatitis A or B). 6. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination. Immune System 1. Immunosuppressive medications (e.g. any formulation of corticosteroids) received within 6 months before first vaccination 2. Serious adverse reactions to vaccines including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. 3. Immunoglobulin received within 90 days before first vaccination (for mAbs see criterion 2 in “Vaccines and other Injections” above). 4. Autoimmune disease, current or history 5. AESIs: A participant with a history of a potential immune-mediated medical condition (PIMMC), either ongoing or resolved. Specific examples are listed in Appendix H. 6. History of anaphylaxis, and any allergies that have ever required corticosteroids or visits to the emergency department. 7. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema 8. Immunodeficiency: Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator Clinically significant medical conditions 1. 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 condition specifically listed among the exclusion criteria below. 2. 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 for example tattoos, skin conditions at the injection sites, or a volunteer’s ability to give informed consent. 3. Psychiatric condition and substance abuse 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. 4. Current anti-tuberculosis (TB) prophylaxis or therapy 5. Chronic inflammatory conditions such as asthma 6. Diabetes mellitus type 1 and type 2. (not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes) 7. Thyroidectomy, or thyroid disease 8. 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 mmHg 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 enrolment. 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 enrolment or diastolic blood pressure ≥ 100 mm Hg at enrolment. 9. Bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions). 10. Malignancy - current or historic. 11. Seizure disorder: History of seizure(s). Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time. 12. Asplenia: any condition resulting in the absence of a functional spleen. 13. History of angioedema or anaphylaxis 14. History of generalized urticaria. 15. On-going or chronic use of medications, like NSAIDS, Aspirin, ACE inhibitors or antihistamines. 5.3 Participant departure from vaccination schedule or withdrawal This section concerns an individual participant’s departure from the study product administration schedule. Pause rules for this study are described in Section 11. 5.3.1 Delaying vaccinations for a participant Under certain circumstances, a participant’s scheduled vaccination will be delayed. The factors to be considered in such a decision include but are not limited to the following: ● Within 45 days prior to any study injection: ⮚ Receipt of blood products or immunoglobulin ● Within 30 days prior to any study injection ⮚ Receipt of live attenuated vaccines ⮚ Receipt of allergy treatment with antigen injections ● Within 14 days prior to any study injection ⮚ Receipt of any vaccines that are not live attenuated vaccines (e.g., pneumococcal) ● Pre-vaccination abnormal vital signs or clinical symptoms that may mask or complicate the assessment of vaccine reaction In order to avoid vaccination delays and missed vaccinations, participants who plan to receive licensed vaccines or allergy treatments should be counselled to schedule receipt of these products outside the intervals indicated above. The effects of these substances on safety and immunogenicity assessments and their interactions with study vaccines are unknown. |
Adult: 18 Year(s)-44 Year(s) |
18 Year(s) |
40 Year(s) |
Both |