Safety, Tolerability, and Immunogenicity Study of Homologous Ad26 Mosaic Vector Vaccine Regimens or Heterologous Ad26 Mosaic and MVA Mosaic Vector Vaccine Regimens With Glycoprotein 140 (gp140) for Human Immunodeficiency Virus (HIV) Prevention

An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the study vaccine. An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.

Time frame: Serious adverse events (SAEs) were reported up to Week 336 for Group 1 and 2 and up to Week 96 for the other groups (Group 3, 4, 5, 6, 7, and 8). Other adverse events (AEs) were reported for the main study period up to Week 96 for all the groups

Population: The FAS included all randomized participants with at least one study vaccine administration documented regardless of the occurrence of protocol deviations.

Solicited local AEs (at injection site) included erythema, induration, swelling, itching and warmth were collected within 7 days after vaccination.

Time frame: Up to Week 49 (7 days post any dose)

Population: The FAS included all randomized participants with at least one study vaccine administration documented regardless of the occurrence of protocol deviations.

Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), headache, fatigue, myalgia, nausea, vomiting were collected within 7 days after vaccination.

Time frame: Up to Week 49 (7 days post any dose)

Population: The FAS included all randomized participants with at least one study vaccine administration documented regardless of the occurrence of protocol deviations.

Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.

Time frame: Up to Week 52 (28 days post vaccination)

Population: The FAS included all randomized participants with at least one study vaccine administration documented regardless of the occurrence of protocol deviations.

The Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)- specific binding antibody titer were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (\>) lower limit of quantification (LLOQ) if baseline less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline greater than or equal to (\>=) LLOQ. The lower limits of quantification (LLOQs) for this assay were 625, 156.25, 625, and 156.25 endotoxin units per milliliter (EU/mL) for Clade A (92UG037.1), Clade B (1990a), Clade C (Con C), and Clade C (C97ZA.012) respectively.

Time frame: Week 28

Population: Per protocol immunogenicity (PPI) analysis set: participants who received at least first 3 vaccines as scheduled, had at least 1 post-vaccination immunogenicity blood draw and not diagnosed with HIV. N(number of participants analyzed): participants who were evaluable for this OM. n(number analyzed): participants evaluable for specified categories.

The human immunodeficiency virus (HIV)-1 BAMA employs flow-cytometric-based technology that also utilizes antibody and antigen interactions to test for the presence of specific antibodies in an unknown sample with the added advantage of multiplexing the antigens of interest. Positive and negative control standards were run with each assay to ensure specificity. The positivity threshold was determined per antigen based on the plus (+) 3 standard deviation (SD) on the non-specific background. Sample values had to be greater than or equal to this value and had to be 3-fold over the baseline values with a minimum median fluorescent intensities (MFI) value of 100. Samples taken after W48 from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.

Time frame: Week 16, 28, 52, 78, and 96

Population: PPI analysis set. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here 'n' (number analyzed) signifies number of participants evaluable at specified time points.

Vaccine-induced binding antibody IgG1, IgG2, IgG3 and IgG4 subclass responses were investigated using Clade C (C97ZA.012) specific ELISAs. The response was defined as post-baseline value \>LLOQ if baseline \<LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline \>=LLOQ. The LLOQs for this assay were 12.3, 28.7, 12.4, and 13.2 for IgG1, IgG2, IgG3 and IgG4 respectively. Samples taken after Week 48 (W48) from PPI set, who missed 4th vaccine or deviated schedule were excluded. As planned, the data reported for this endpoint at specified time points only for each reported category.

Time frame: Week 28, 52 and 96

Population: PPI analysis set. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here 'n' (number analyzed) signifies number of participants evaluable at specified time points.