Evaluating the Safety and Immune Response to Two Pneumococcal Vaccines in HIV-Infected Pregnant Women
- Conditions
- Pneumococcal InfectionsHIV Infections
- Interventions
- Biological: PPV-23 VaccineBiological: PCV-13 VaccineBiological: Placebo Vaccine
- Registration Number
- NCT01443117
- Brief Summary
HIV-infected people and pregnant women are at risk of developing severe pneumococcal disease. The purpose of this study is to compare the safety and immune response to two pneumococcal vaccines in HIV-infected pregnant women.
- Detailed Description
Pneumococcus is the most common bacterial opportunistic infection in HIV-infected children, and it is the leading cause of bacterial pneumonias in HIV-infected pregnant and non-pregnant adults. Pneumococcal polysaccharide vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-13) are two vaccines used for the prevention of pneumococcal (PNC) disease. The PPV-23 vaccine is recommended by the Centers for Disease Control and Prevention (CDC) for HIV-infected adults, including HIV-infected pregnant women. The PCV-13 vaccine is recommended by the CDC for use in children, including HIV-infected children. Studies have shown that PCV-13 and vaccines like PCV-13 are safe for use in healthy pregnant women, but they have not been studied in HIV-infected pregnant women. This study will compare the safety and immune response to the PCV-13 and PPV-23 vaccines in HIV-infected pregnant women.
This study will enroll HIV-infected pregnant women in their second or third trimester who are receiving antiretroviral therapy. The study will take place in two steps. In Step 1, participants will be randomly assigned to receive PPV-23 vaccine, PCV-13 vaccine, or placebo vaccine. At a baseline study visit, participants will undergo a physical examination, medical history and nutritional status review, fetal heart rate measurement, blood collection, an ultrasound, an adherence questionnaire, and a nose and throat swab procedure. They will then receive their assigned vaccine. Participants will not be told which vaccine they are receiving. Participants will remain in the clinic for 30 to 60 minutes after receiving the vaccine for monitoring. They will attend study visits 14 to 21 days after the vaccination visit, at Week 8, and at the time of labor and delivery. During these visits, they will undergo select baseline study procedures. After delivery, participants' babies will have a physical examination and blood collection. At 2 and 4 months after delivery, participants' babies will undergo select baseline study procedures. Participants' babies will receive the PCV vaccine according to the local standard of care.
Step 2 of the study will begin 6 months after delivery, at which time participants and their babies will attend a study visit for a physical examination, medical history and nutritional status review, an adherence questionnaire, and blood collection. Participants who received the PPV-23 vaccine or the PCV-13 vaccine in Step 1 will end their participation in the study after this visit. Participants who received placebo vaccine in Step 1 will be randomly assigned to receive the PPV-23 vaccine or PCV-13 vaccine at this study visit but will not be told which vaccine they are receiving. Participants will attend a study visit 14 to 21 days after receiving the vaccine, which will include select study procedures.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Step 2: PPV-23 Vaccine (Arm 2a) PPV-23 Vaccine Participants will receive one IM injection of 0.5 mL of the PPV-23 vaccine 6 months after delivery. Step 2: PCV-13 Vaccine (Arm 2b) PCV-13 Vaccine Participants will receive one IM injection of 0.5 mL of the PCV-13 vaccine 6 months after delivery. Step 1: PCV-13 Vaccine (Arm 1b) PCV-13 Vaccine Participants will receive one IM injection of 0.5 mL of the PCV-13 vaccine at baseline. Step 1: PPV-23 Vaccine (Arm 1a) PPV-23 Vaccine Participants will receive one intramuscular (IM) injection of 0.5 mL of the PPV-23 vaccine at baseline. Step 1: Placebo Vaccine (Arm 1c) Placebo Vaccine Participants will receive one IM injection of 0.5 mL of the placebo vaccine at baseline.
- Primary Outcome Measures
Name Time Method For women: Grade 3 or higher adverse events Measured through approximately 60 weeks For women: Pneumonia or invasive pneumococcal disease Measured through approximately 60 weeks For infants: Congenital defects Measured through approximately 36 weeks For infants: Immune interference with infant response to PCV vaccine Measured through approximately 36 weeks For women: Significant changes in HIV viral load in pregnant participants Measured through approximately 60 weeks For women: Grade 3 or higher adverse events judged to be at least possibly related to the study treatment Measured through approximately 60 weeks For women: A 2-fold increase in ELISA or 4-fold rise in opsonic activity (OPA)-measured antibody concentrations Measured at 14 to 21 days after immunization IgG antibodies to pneumococcal (PNC) 19A, 6B, 18C, and 5 will be measured by enzyme-linked immunosorbent assay (ELISA) and the capacity to opsonize to 19A and 6B will also be measured by OPA. The primary endpoint is a response to 3 out of 4 serotypes. A greater than or equal to 4-fold increase in OPA- and/or a greater than or equal to 2-fold increase in ELISA-measured IgG antibodies against PNC 19A and 6B will define a response against these serotypes. Responses to PNC 18C and 5 will rely only on the ELISA results.
For infants: ELISA-measured IgG antibody levels greater than or equal to 0.35ug/mL or OPA-measured antibody titers greater than or equal to 1:8 Measured at 8 weeks of age for infants Reaching this level of antibodies for 3 of the 4 PNC serotypes that will be tested defines success
For women: Grade 3 or higher pregnancy-specific systemic adverse events Measured through approximately 60 weeks For infants: Pneumonia or invasive pneumococcal disease Measured through approximately 36 weeks For infants: In-utero or perinatal HIV infection Measured through approximately 36 weeks
- Secondary Outcome Measures
Name Time Method Infant maternal antibodies at 2 months of life Measured at 2 months of age for infants Maternal and infant vitamin D levels Measured through approximately 60 weeks