Background: Group B Streptococcus (GBS) is a common bacterium that many adults carry without knowing. However, it can be very dangerous for newborn babies. GBS can cause serious infections that may lead to disability or even death. Around the world, GBS causes hundreds of thousands of infections in babies every year and tens of thousands of deaths. The biggest burden is seen in African countries. This is why preventing GBS in pregnant women and their babies is very important. GBS is found in the vagina and rectum of about 1 in 10 to 1 in 3 people. During pregnancy, the bacteria can reach the baby before birth or infect the baby during labour and delivery. GBS can also cause illness in pregnant women, including bloodstream infections, infections of the womb, stillbirth, or preterm birth. Protecting mothers and babies from GBS remains a major health need. 

How the study will be done: This is a large international Phase 3 study testing a new vaccine (GBS6) meant to protect mothers and their babies from Group B Streptococcus. Pregnant women between 24 and 36 weeks will be randomly given either the vaccine or a placebo. They will then be followed for about six months after giving birth. Some adolescent mothers may also take part, with their assent and their parental/legal guardian permission per local regulations. A staggered enrollment approach based on GA at the time of study vaccination will be utilized. Enrollment will start with eligible pregnant women in the first of 3 groups: (1) 32 0/7 to 36 0/7 weeks of gestation, followed by (2) 28 0/7 to <32 0/7 weeks of gestation, and then (3) 24 0/7 to <28 0/7 weeks of gestation. While enrollment for a GA group is ongoing, progression to the subsequent GA group will be determined after an external data monitoring committee review of at least 300 maternal deliveries in the enrolled GA group(s). Global cumulative data will be reviewed, but enrollment by region (high income or low and middle income as defined by the SAP) cannot progress to a subsequent GA group until at least 150 maternal deliveries have been reviewed by the EDMC in enrolled GA group(s) in that region. Enrolment will be spread evenly across the three pregnancy groups and across high-income and lower-income countries.  

Number of Participants: Approximately 6000 pregnant volunteers and their infants who provided informed consent, or their legally authorized representative’s agreement, to participate in the study will be enrolled in the study.  

Study Site: The study will be conducted by Victoria Biomedical Research Institute (VIBRI) at the Kisumu County Referral Hospital Clinical Research Centre. We expect approximately to enroll about 75 participants who qualify for the study. 

Expected Results:

The results of this study will add to the evidence regarding the safety and tolerability of the GBS6 vaccine in pregnant women and their infants, assess how well the vaccine helps mothers produce protective antibodies and how many of these antibodies are transferred to their babies. The study will also evaluate how infants respond to routine childhood vaccinations—such as diphtheria-containing and pneumococcal vaccines.  

A subset of infants will be asked to take part in the study for up to 19 months. The subset will receive diphtheria toxoid-containing vaccine and/or pneumococcal vaccine following each country's standard immunization plan and have blood drawn 1 month after completion of the primary and/or toddler (booster) doses. however, the VIBRI site will not participate in the infant vaccine immunogenicity subset. 

Purpose and rationale: Prevention of group B streptococcus (GBS) disease in pregnant women and their infants is a significant unmet medical need. Streptococcus agalactiae (known as GBS) is an encapsulated gram-positive bacterial pathogen that is a leading cause of invasive infections in young infants and is a significant cause of infant morbidity and mortality globally.  A group B streptococcus 6-valent polysaccharide conjugate vaccine (GBS6) is being developed for prevention of invasive disease in infants caused by the 6 most prevalent GBS serotypes (Ia, Ib, II, III, IV, and V) by active immunization of pregnant women. 

Primary Objective(s):

1.Primary Safety

• To describe the safety and tolerability of GBS6 in maternal participants. 

• To assess the safety of maternal immunization in infant participants born to pregnant women who were vaccinated with GBS6 during pregnancy. 

2. Primary Immunogenicity

• To assess the ability of GBS6 to induce anti-CPS IgG antibody levels predicted to provide protection from invasive GBS LOD caused by the 6 vaccine serotypes (Ia, Ib, II, III, IV, and V) in infants when GBS6 is administered to healthy pregnant women. 

• To assess the ability of GBS6 to induce anti-CPS IgG antibody levels predicted to provide protection from invasive GBS EOD caused by the 6 vaccine serotypes (Ia, Ib, II, III, IV, and V) in infants when GBS6 is administered to healthy pregnant women. 

• To evaluate the aggregate predicted VE combining all 6 serotypes in GBS6 to provide protection from invasive GBS LOD based on serotype-specific anti-CPS IgG concentrations measured in infants at birth. 

• To evaluate the aggregate predicted VE combining all 6 serotypes in GBS6 to provide protection from invasive GBS EOD based on serotype-specific anti-CPS IgG concentrations measured in infants at birth. 

Secondary Objective(s)

1 Secondary Immunogenicity

• To assess the ability of GBS6 to induce OPA titers at birth in infant participants born to maternal participants vaccinated with GBS6. 

• To describe anti-CPS IgG antibody levels predicted to provide protection from invasive GBS disease (all disease) caused by the 6 individual vaccine serotypes in infants when GBS6 is administered to healthy pregnant women. 

• To describe anti-CPS IgG antibody levels in infant participants born to maternal participants vaccinated with GBS6. 

• To describe anti-CPS IgG antibody levels predicted to provide protection from invasive GBS LOD and EOD, separately, caused by the 6 individual vaccine serotypes (Ia, Ib, II, III, IV, and V) in infants when GBS6 is administered to healthy pregnant women. 

• To further describe the immunogenicity of GBS6 in maternal participants when administered to healthy pregnant women. 

• To describe serum IgG responses to active immunization with diphtheria toxoid–containing vaccine and PCV in infant participants born to maternal participants vaccinated with GBS6 versus placebo. 

Study design

This is a global Phase 3, multicenter, randomized, placebo-controlled, double-blinded study to assess the safety, tolerability, and immunogenicity of a hexavalent capsular polysaccharide conjugate group B streptococcus vaccine, GBS6, in healthy pregnant women and their Infants.

Note: The term “pregnant women” in this study includes pregnant adolescents <18 years of age. 

Study-eligible pregnant women who are between 24 0/7 and 36 0/7 weeks of gestation will receive either GBS6 (20 µg CPS/serotype conjugate/dose) or placebo at Visit 1. Once they have provided informed consent, the pregnant women will be referred to as “maternal participant” and will be followed from receipt of study intervention during pregnancy until 6 months after delivery.  

Infants born to maternal participants will be referred to as “infant participants”.  After birth, the majority of infant participants will have 3 additional scheduled study visits for safety follow-up during their 12 months of participation.  

Study Population:

Approximately 6000 maternal participants and their infants (12000 participants overall) will be enrolled in the study. 

Maternal participants will include adolescent pregnant women who are considered “minors.” Information/assessments for minors will require minor participants’ assent and their parental/legal guardian awareness/approval per local regulations