Safety and Immunogenicity of Anti-Pneumococcal Vaccines in HIV-Infected Pregnant Women
Condition: PNC Vaccine; HIV-infected Pregnant Women
Intervention: PPV-23; PCV-10; NaCl
Intervention description: PPV-23 was a polysaccharide PNC vaccine, licensed in Brazil, directed against 23 serotypes.; PCV-10 was a conjugate PNC vaccine, licensed in Brazil, directed against 10 serotypes.; NaCl was the placebo for the study against which the two vaccines were compared during pregnancy.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 347.0
Sex: Female
Healthy volunteers: No
Keywords: PPV-23; PCV-10; HIV; Immunization; Pregnancy

Summary:

      The purpose of this study was to determine the safety, reactogenicity, immunogenicity,
      transplacental antibody transfer and interference with infant responses to childhood
      vaccination of maternal vaccination with pneumococcal conjugate 10-valent vaccine (PCV-10) or
      pneumococcal polysaccharide 23-valent vaccine (PPV-23) by comparison with placebo.
    

Eligibility criteria:

        Step 1 Inclusion Criteria for Pregnant Women:

          1. Pregnant women ≥ 18 years old who provided written informed consent prior to study
             initiation.

          2. Pregnant women < 18 years old with parent or legal guardian able and willing to
             provide signed informed consent, or who had the capacity to consent for themselves, as
             defined by the local Institutional Review Board (IRB), and who provided written
             informed consent prior to study initiation.

          3. Gestational age [≥ 14 weeks (14 weeks 0 days) to < 33 weeks (32 weeks 6 days)]
             documented by the approximate date of the last menstrual period and corroborated by
             ultrasound if obtained as per local standard of care. Results of the ultrasound were
             recorded on the Abdominal Ultrasound Form.

          4. Documentation of HIV-1 infection defined as positive results from two samples
             collected at different time points as per standard of care. Results and source
             documentation may have been obtained from the medical records.

          5. Receipt of HAART (a regimen of at least three ARV drugs) for ≥ 4 weeks prior to
             enrollment.

          6. Documented platelet count of > 50,000/mm3 and an absolute neutrophil count (ANC) of >
             500/ mm3 ≤ 28 days prior to study entry.

          7. Women who were willing and able to comply with the study visits.

        Step 1 Exclusion Criteria for Pregnant Women:

          1. Receipt of any PCV or PPV-23 at any time prior to enrollment, documented by medical
             history or record.

          2. Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2
             weeks prior to study entry.

          3. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or
             medication) ≤ 4 weeks prior to enrollment in this study, or expectations to receive
             another non-licensed agent before delivery unless approval from the protocol team is
             obtained.

          4. Any significant (in the opinion of the site investigator) acute illness and/or oral
             temperature greater than or equal to 100.4 degrees F ≤ 24 hours prior to study entry.

          5. Women who planed to terminate their pregnancy.

          6. Women who had a prior history of lupus or other autoimmune disorders.

          7. Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study
             enrollment, or evidence of immunosuppression as a result of an underlying illness
             (other than HIV-1 infection) or treatment.

          8. Ongoing neoplastic disease (excluding non-melanoma skin cancer, and human papilloma
             virus-related cervical dysplasia, cervical intraepithelial neoplasia (CIN) grades 1, 2
             or 3).

          9. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day
             or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 12 weeks of
             study entry.

         10. Women who received last dose of corticosteroids for preterm labor ≤ 1 week prior to
             study entry. Note: A woman can be enrolled if more than 1 week has elapsed from the
             last dose of corticosteroids, i.e., enrollment may be delayed to satisfy this
             criterion.

         11. Receipt of immunoglobulin or other blood products (with exception of Rho D immune
             globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive
             immunoglobulin or other blood products (with the exception of Rho D immune globulin)
             during pregnancy or for the first 24 weeks after delivery.

         12. Receipt of Interleukin-2 (IL2), interferon (IFN), granulocyte-macrophage
             colony-stimulating factor (GMCSF) or other immune mediators ≤ 12 weeks before
             enrollment.

         13. History of a severe adverse reaction to inactivated polysaccharide or conjugated
             vaccines.

         14. Any condition that would, in the opinion of the site investigator, place the
             participant at an unacceptable risk of injury or render the participant unable to meet
             the requirements of the protocol.

         15. Pregnancy complications (in the current pregnancy) such as pre-term labor, and
             pre-eclampsia or any other pregnancy related complication, which in the opinion of the
             investigator might jeopardize the results of the study.

         16. Chronic hepatitis B infection that may require administration of Hepatitis B
             Hyperimmune Globulin to neonates.

        Step 2 Inclusion Criteria for Women:

          1. 24 weeks ± 4 weeks postpartum.

          2. Completion of Step 1.

          3. Receipt of placebo on Step 1.

        Step 2 Exclusion Criteria for Women:

          1. Pregnancy.

          2. Receipt of any live licensed vaccine ≤ 4 weeks or inactivated licensed vaccine ≤ 2
             weeks prior to Step 2 entry.

          3. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or
             medication) ≤ 4 weeks prior to vaccination, or expects to receive another non-licensed
             agent within 28 days after vaccination.

          4. Any significant (in the opinion of the site investigator) acute illness and/or oral
             temperature greater than or equal to 100.4 degrees F within 24 hours of entry except
             when, in the opinion of the physician, withholding the agent entails even greater
             risk.

          5. Use of anti-cancer systemic chemotherapy or radiation therapy or has developed
             immunosuppression as a result of an underlying illness (other than HIV-1 infection) or
             treatment.

          6. Use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or
             equivalent for more than 2 consecutive weeks (or 2 weeks total) within 2 weeks of
             entry in Step 2.

          7. Receipt of immunoglobulin or other blood products (with exception of Rho D immune
             globulin) within 12 weeks prior to entry in Step 2 or is scheduled to receive
             immunoglobulin or other blood products (with the exception of Rho D immune globulin)
             during the 28 days following vaccination.

          8. Receipt of IL2, IFN, GMCSF or other immune mediators ≤ 12 weeks before entry in Step
             2.

        Step 3 Inclusion Criteria for Women

          1. 24 weeks ± 4 weeks postpartum.

          2. Completion of Step 1.

          3. Receipt of placebo on Step 1.

          4. Met Step 2 exclusion criterion of pregnancy.

        Step 3 Exclusion Criteria for Women

        None.