Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults

NCT03039491 | Completed Early Phase 1 FDA Drug

• 1 other identifier: MUSC vaccine study
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesized that pneumococcal vaccination with either the 23-valent pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody levels/functional antibody activity and induce similar pneumococcal polysaccharide (PPS)-specific B cell response in HIV positive individuals \> 50 years of age, HIV positive individuals 21-40 years of age as compared to HIV negative \> 50 years of age. The investigators immunized the study groups HIV+ persons \>50, HIV+ persons 21-40 and controls (HIV negative) with PCV 13 followed by PPV23 and HIV\>50 with PPV alone and examined immune responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody levels and OPA and compared to populations immunized with PPV

Conditions

HIV Lipodystrophy; Aging

Keywords

pneumococcal vaccination

Outcome Measures

Primary Outcomes (2)

• Antibody response

  Measure antibody response by ELISA (ug/mL)

  Change in ug/mL from day 0 to 30 days after receipt of PPV23

• opsonophagocytic antibody activity

  opsonophagocytic antibody response measured by opsonophagocytic assay (OPA)

  Change in opsonophagocytic titer from day 0 to 30 days after receipt of PPV23

Secondary Outcomes (20)

• PPS-specific B cell phenotype

  Change from day 0 to day 7 post-vaccination

• PPS-specific B cell phenotype

  Change from day 56 to day 63 post-vaccination

• Expression of TACI on PPS-specific B cells

  change from day 0 to day 7

• Expression of TACI on PPS-specific B cells

  change from day 56 to day 63

• Expression of BAFFR on PPS-specific B cells

  change from day 0 to day 7

Study Arms (8)

HIV+ 50-65, CD4>200 PCV/PPV

EXPERIMENTAL

HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

HIV+ 50-65, CD4<200 PCV/PPV

EXPERIMENTAL

HIV+ individuals , 50-65 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

HIV+ 50-65, CD4>200 PPV

EXPERIMENTAL

HIV+ individuals , 50-65 years of age with a nadir CD4 count \>200 to receive PPV23 only Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent

HIV+ 50-65, CD4<200 PCV

EXPERIMENTAL

HIV+ individuals , 50-65 years of age with a nadir CD4 count \<200 to receive PPV23 only Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent

HIV- 50-65, PCV/PPV

ACTIVE COMPARATOR

HIV- individuals , 50-65 years of age immunized with PCV13 followed by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

HIV- 50-65, PPV

ACTIVE COMPARATOR

HIV- individuals, 50-65 years of age immunized with PPV23 only. Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent

HIV+ 21-40, CD4>200 PCV/PPV

ACTIVE COMPARATOR

HIV+ individuals , 21-40 years of age with a nadir CD4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

HIV+ 21-40, CD4<200 PCV/PPV

ACTIVE COMPARATOR

HIV+ individuals , 21-40 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

Interventions

Pneumococcal polysaccharide vaccine 23 valent BIOLOGICAL

This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae

Also known as: Pneumovax

HIV+ 21-40, CD4<200 PCV/PPV; HIV+ 21-40, CD4>200 PCV/PPV; HIV+ 50-65, CD4<200 PCV; HIV+ 50-65, CD4<200 PCV/PPV; HIV+ 50-65, CD4>200 PCV/PPV; HIV+ 50-65, CD4>200 PPV; HIV- 50-65, PCV/PPV; HIV- 50-65, PPV

13 valent conjugated pneumococcal vaccine BIOLOGICAL

This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197

Also known as: Prevnar 13

HIV+ 21-40, CD4<200 PCV/PPV; HIV+ 21-40, CD4>200 PCV/PPV; HIV+ 50-65, CD4<200 PCV/PPV; HIV+ 50-65, CD4>200 PCV/PPV; HIV- 50-65, PCV/PPV

Eligibility Criteria

• Age: 21 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Previous immunization with pneumococcal vaccine less than 5 years ago
• pregnancy and absence of contraceptive practice in women of childbearing age and breast feeding
• known anaphylaxis, hypersensitivity to the pneumonia vaccine
• those who received blood products or gammaglobulin in last 3 months
• inability to comprehend or sihn informed consent
• Medications known to affect immune function (chemotherapy, an angiotensin-converting-enzyme (ACE) inhibitors, corticosteroids, anti-TNFalpha agents)
• previous disease/present illness that may affect response to vaccination: previous pneumococcal disease, removal of spleen, auto-immune disease, end stage renal disease (ESRD) or end stage liver disease, cancer)
• significant (3x upper limit of normal) in complete blood count (CBC), chemistries, immunoglobulin levels

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (7)

• Crum-Cianflone NF, Huppler Hullsiek K, Roediger M, Ganesan A, Patel S, Landrum ML, Weintrob A, Agan BK, Medina S, Rahkola J, Hale BR, Janoff EN; Infectious Disease Clinical Research Program HIV Working Group. A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults. J Infect Dis. 2010 Oct 1;202(7):1114-25. doi: 10.1086/656147.

  PMID: 20795819 BACKGROUND

• de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis. 2008 Apr 1;46(7):1015-23. doi: 10.1086/529142.

  PMID: 18444818 BACKGROUND

• French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010 Mar 4;362(9):812-22. doi: 10.1056/NEJMoa0903029.

  PMID: 20200385 BACKGROUND

• Baxendale HE, Keating SM, Johnson M, Southern J, Miller E, Goldblatt D. The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly. Vaccine. 2010 Jul 5;28(30):4763-70. doi: 10.1016/j.vaccine.2010.04.103. Epub 2010 May 14.

  PMID: 20471437 BACKGROUND

• Penaranda M, Payeras A, Cambra A, Mila J, Riera M; Majorcan Pneumococcal Study Group. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AIDS. 2010 May 15;24(8):1226-8. doi: 10.1097/QAD.0b013e3283389de5.

  PMID: 20299956 BACKGROUND

• Khaskhely N, Mosakowski J, Thompson RS, Khuder S, Smithson SL, Westerink MA. Phenotypic analysis of pneumococcal polysaccharide-specific B cells. J Immunol. 2012 Mar 1;188(5):2455-63. doi: 10.4049/jimmunol.1102809. Epub 2012 Jan 23.

  PMID: 22271652 BACKGROUND

• Happe M, Samuvel DJ, Ohtola JA, Korte JE, Westerink MAJ. Race-related differences in functional antibody response to pneumococcal vaccination in HIV-infected individuals. Vaccine. 2019 Mar 14;37(12):1622-1629. doi: 10.1016/j.vaccine.2019.01.084. Epub 2019 Feb 21.

  PMID: 30797636 DERIVED

MeSH Terms

Interventions

Pneumococcal Vaccines; 13-valent pneumococcal vaccine

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Maria A. Julia Westerink, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2017
• First Posted: February 1, 2017
• Study Start: September 1, 2015
• Primary Completion: March 30, 2020
• Study Completion: March 30, 2020
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)