A randomised, placebo-controlled, double-blind study to evaluate the safety, tolerability and immunogenicity of the GBS-NN/NN2 (Recombinant protein vaccine against Group B Streptococcus) vaccine in women living with HIV and women without HIV, and their newborn babies from vaccination up to delivery/birth. Mothers and babies will be followed up for 12 months post-delivery.
100 women who are pregnant and living with HIV will randomly receive two 0.5 mL (millilitre) intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women). 100 women who are pregnant and do not have HIV will randomly receive two 0.5 mL intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women). Participants will be screened at 24 to 28 weeks gestation (Days -14 to Day -1) and the groups will be dosed in parallel. The first dose of vaccine or placebo will be administered at Day 0 and the second dose will be administered 28±2 days later. Delivery is anticipated to be approximately 10 to 14 weeks after the first dose of vaccine. For the analysis of the immune response, the placebo groups will be combined. For safety, the placebo groups will be analysed separately and will be combined for comparison with the potential vaccine groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
200
GBS-NN/NN2 bound to Alhydrogel as an adjuvant.
Normal Saline 0.9%
Empilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital
Johannesburg, South Africa
University of the Witwatersrand, Johannesburg (Respiratory and Meningeal Pathogens Research unit)
Johannesburg, South Africa
MUJHU Research Collaboration/MUJHU Care Ltd, Kawempe National Referral Hospital
Kawempe, Uganda
Incidence of Treatment Emergent Adverse Events (TEAEs) in Maternal Participants
Incidence of all TEAEs in maternal participants from first vaccination up to 28 days post-delivery.
Time frame: From first vaccination (26 to 30 weeks of gestation) up to 28 days post-delivery, up to 24 weeks
Incidence of Adverse Events (AEs) in Newborn Babies
Incidence of AEs in Newborn babies From birth to first visit after birth (visit 6).
Time frame: From birth to first visit after birth (28±4 days post-delivery)
Number of Maternal Participants With Solicited Local AEs Within 7 Days After Each Study Vaccine Dose
Number of maternal participants with solicited local AEs within 7 Days after each study vaccine dose, defined as: injection site redness, bruising, swelling, itching, pain and tenderness. Injection-site redness was graded based on measurements in centimeter (cm) as grade 0 (no visible redness), grade 1 (mild; 0-2 cm), grade 2 (moderate; 2.1-5 cm) or grade 3 (severe; \> 5 cm). Swelling was graded as grade 0 (no swelling detected), grade 1 (palpable "firmness" only), grade 2 (0-4 cm) or grade 3 (\> 4 cm). Pain at the injection site was rated on a visual analogue scale of 0 to 10, where 0 is no pain and 10 is extreme pain/worst possible pain. Bruising, itching and tenderness were categorised as either yes (present) or no (absent).
Time frame: For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline)
Number of Maternal Participants With Solicited Systemic AEs Within 7 Days After Each Study Vaccine Dose
Number of maternal participants with solicited systemic AEs within 7 days after each study vaccine dose, defined as: headache, sore throat, "flu-like" symptoms, muscle aches, fever in the 72 hours post dose.
Time frame: For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline)
Gestational Age of Newborn Baby
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Gestational age of newborn baby
Time frame: At birth
Weight of Newborn Baby
Weight of newborn baby
Time frame: At birth
Length of Newborn Baby
Length of newborn baby
Time frame: At birth
Head Circumference of Newborn Baby
Head circumference of newborn baby
Time frame: At birth
Apgar Score for Newborn Baby
APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of newborn baby were measured at 1, 5 and 10 minutes. The APGAR score is a rapid clinical assessment tool used immediately after birth to evaluate a newborn's physical condition. It evaluates five criteria : Appearance (skin color), Pulse (heart rate), Grimace (Reflex irritability), Activity (muscle tone), Respiration (breathing effort), each category is scored 0, 1, or 2, where 2 indicates optimal function. Total score ranges from 0 to 10: 7-10: Normal / Reassuring - baby adapting well 4-6: Moderately abnormal - may need assisted breathing or additional monitoring 0-3: Low - requires immediate resuscitation and urgent intervention
Time frame: At birth
Transfer Rate (Baby/Mother) of IgG Antibody Concentrations
For each of the specific IgG antibody concentrations, the transfer rate is defined as concentration in baby at birth/concentration in mother at delivery, expressed as a percentage.
Time frame: At delivery
Incidence of Significant Adverse Reactions in Mothers
Incidence of significant adverse reactions in maternal participants
Time frame: From delivery to 6 months post-delivery
Developmental Milestones of Babies
Developmental milestones at 6 months were assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3), a validated developmental screening tool designed to evaluate early childhood development across 5 key domains: communication, gross motor, fine motor, problem solving, and personal-social. Each domain includes 6 items scored as Yes (10), Sometimes (5), or Not yet (0). Domain scores are calculated by summing item scores (range: 0-60 per domain); higher scores indicate better development. A total score (sum of all domains) may be calculated (range: 0-300), though interpretation relies primarily on domain scores. For each domain, the cut-offs are 29.65 for Communication, 22.25 for Gross Motor, 25.14 for Fine Motor, 27.72 for Problem Solving, and 25.34 for Personal-Social. Scores above these thresholds generally indicate development on schedule, while scores near the cutoff suggest monitoring, and scores below warrant additional assessment or referral.
Time frame: At 6 months
Geometric Mean Antibody Concentration in Maternal Participants (4 Weeks)
Geometric mean IgG antibody concentration in the maternal participants specific to Alpha Like Protein 1 (Alp1), Alpha Like Protein 2 (Alp2), Alpha Like Protein C (AlpC) and Rib protein (Rib).
Time frame: At 4 weeks post first injection and at 4 weeks post second injection
Geometric Mean Antibody Concentration in Maternal Blood at 6 Months Post-delivery
Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in maternal blood at 6 months post-delivery
Time frame: 6 months post-delivery
Geometric Mean Antibody Concentration in Infant Blood at 1, 2, and 3 Months Post-delivery
Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in infant blood at 1, 2, and 3 months post-delivery
Time frame: At 1, 2, and 3 months post-delivery
Geometric Mean Antibody Concentration in Newborns
Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in newborn blood within 48 hours of birth.
Time frame: Within 48 hours of birth.
Geometric Mean Antibody Concentration From Maternal Blood at Delivery
Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib from maternal blood at delivery
Time frame: At delivery
Geometric Mean Fold Increase in Antibody Concentration in Maternal Blood
Geometric mean fold increase in IgG specific antibody concentration (Alp1, Alp2, AlpC and Rib) in maternal blood from baseline to 4 weeks after vaccination with the first and second dose.
Time frame: At 4 weeks post first injection and at 4 weeks post second injection
Geometric Mean Fold Increase in Antibody Concentration in Maternal Blood
Geometric mean fold increase in IgG specific antibody concentration (Alp1, Alp2, AlpC and Rib) in maternal blood from baseline to delivery.
Time frame: Baseline (Gestational Age 26 to 30 weeks) pre-vaccination to delivery, up to 24 weeks
Proportion of Mothers Achieving Vaccine Specific IgG Antibody Concentrations
Proportion of mothers achieving vaccine specific IgG antibody concentrations in maternal samples respectively, above pre-defined arbitrary thresholds (0.5, 1, 2 μg/mL).
Time frame: At delivery
Proportion of Newborn Babies Achieving Vaccine Specific IgG Antibody Concentrations
Proportion of newborn babies achieving vaccine specific IgG antibody concentrations above pre-defined arbitrary thresholds (0.5, 1, 2 μg/mL).
Time frame: At birth