Humoral Determinants of Immunity to Pneumococcal Infection

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Daniel M. Musher MD, VA Medical Center, Houston
ClinicalTrials.gov Identifier:
NCT00304382
First received: March 16, 2006
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to determine whether there are differences in the level of antibody to capsular polysaccharides of S. pneumoniae or the physiological activity of such antibody after vaccinating patients who have recovered from pneumococcal pneumonia with pneumococcal polysaccharide vaccine (Pneumovax) or conjugate pneumococcal vaccine (Prevnar).


Condition Intervention Phase
Pneumonia
Pneumococcal Infections
Infections, Streptococcus Pneumoniae
Biological: Prevnar
Biological: Pneumovax
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Humoral Determinants of Immunity to Pneumococcal Infection

Resource links provided by NLM:


Further study details as provided by VA Medical Center, Houston:

Primary Outcome Measures:
  • Serum will be used to measure antibody to capsular polysaccharide by ELISA and opsonophagocytic activity [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum will be used to measure antibody to capsular polysaccharide by ELISA and opsonophagocytic capacity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 114
Study Start Date: January 2003
Study Completion Date: June 2012
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PPV-PCV
Patients receive Pneumovax, and 6 months later Prevnar
Biological: Prevnar
0.5 ml IM into each deltoid muscle one time (or two in group PCV-PCV)
Other Name: Pneumococcal 7-Valent Conjugate Vaccine
Biological: Pneumovax
0.5 ml IM one time
Other Name: Pneumococcal Vaccine Polyvalent
Experimental: PCV-PPV
Patients receive Prevnar, and 6 months later Pneumovax
Biological: Prevnar
0.5 ml IM into each deltoid muscle one time (or two in group PCV-PCV)
Other Name: Pneumococcal 7-Valent Conjugate Vaccine
Biological: Pneumovax
0.5 ml IM one time
Other Name: Pneumococcal Vaccine Polyvalent
Experimental: PCV-PCV
Patients receive Prevnar, and 6 months later Prevnar again
Biological: Prevnar
0.5 ml IM into each deltoid muscle one time (or two in group PCV-PCV)
Other Name: Pneumococcal 7-Valent Conjugate Vaccine
Experimental: PCV only
Patients receive Prevnar only
Biological: Prevnar
0.5 ml IM into each deltoid muscle one time (or two in group PCV-PCV)
Other Name: Pneumococcal 7-Valent Conjugate Vaccine

Detailed Description:

Streptococcus pneumoniae (pneumococcus) is the most common cause of pneumonia leading to hospitalization of adults. Resistance to infection is generally thought to be highly associated with antibody to the capsular polysaccharide (CPS). Most people who develop pneumococcal pneumonia lack antibody to the capsule of the infecting type. We have previously shown that some persons develop this infection despite the presence of antibody to the capsular polysaccharide of the infecting type. When such antibody is found, it tends to be poorly functional (DM Musher et al, J Infect Dis 182:158-167, 2000) in that it opsonizes pneumococci poorly for phagocytosis by human white blood cells in vitro, and protects mice poorly or not at all against challenge with the infecting organism.

About 20% of patients with pneumococcal pneumonia in our previous study had been vaccinated with the only vaccine currently in use for adults, namely 23-valent pneumococcal vaccine (Pneumovax [Merck]). This product consists of purified capsular polysaccharides from 23 different serotypes of S. pneumoniae. During the past two years, with more active vaccination programs at our hospital, the proportion of pneumococcal pneumonia patients who have been vaccinated has increased to about 60%. Clearly, the vaccine has not provided a full degree of protection.

After many years of study, including one involving nearly 40,000 children in the Kaiser Permanent health care system, a new form of pneumococcal vaccine was released. In this vaccine, Prevnar [Wyeth-Lederle], capsular polysaccharide from 7 of the most common pneumococcal types were conjugated to a protein that closely resembles diphtheria toxoid. There have been suggestions that Prevnar stimulates antibody in some subjects who fail to respond to Pneumovax (DM Musher et al, Clin Infect Dis 27:1487-1490, 1998) and also that the resulting antibody may more effectively opsonize bacteria for phagocytosis.

We propose to focus the present research on persons who develop pneumococcal pneumonia, a group that is regarded as being at very high risk of reinfection. Persons who recover from pneumococcal pneumonia will be randomized to vaccination revaccination with Pneumovax or vaccination with Prevnar. These studies will clarify whether administration of protein conjugate pneumococcal vaccine stimulates antibody in patients with pneumonia who failed to respond to prior vaccination or stimulates better functional antibody in those who have previously responded with antibody that is only poorly functional.

Our laboratory and others have shown that Prevnar successfully immunizes adults (Ahmed et al, J Infect Dis 173:83-90, 1996). The vaccine is not officially recommended for adults because antibody levels are the same after Prevnar as after Pneumovax. Such antibody may be more functional; this has not yet been determined. Prevnar contains only 7 antigens whereas Pneumovax contains 23 antigens; thus, it would be less desirable, in general, to administer this vaccine instead of Pneumovax. However, in patients who have developed pneumonia despite having received Pneumovax, the conjugate vaccine may offer an opportunity to stimulate production of effective antibody. In the proposed research, all participants will eventually receive both Pneumovax and Prevnar.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of pneumococcal pneumonia
  • Age matched controls who have not had pneumococcal pneumonia
  • Patients enrolled must be veterans

Exclusion Criteria:

  • Patients who do not have the diagnosis of pneumococcal pneumonia based on a clinical syndrome that is consistent with pneumonia and the finding of pneumococcus in blood or sputum or any other sterile site will be excluded
  • Women of child-bearing age will be excluded
  • Patients who have had a prior reaction to pneumococcal vaccine that they describe as 'severe' will be excluded
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00304382

Locations
United States, Texas
Michael E. DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Daniel M. Musher MD
Investigators
Principal Investigator: Daniel M Musher, M.D. Houston VA Medical Center
  More Information

No publications provided

Responsible Party: Daniel M. Musher MD, Chief of ID staff, VA Medical Center, Houston
ClinicalTrials.gov Identifier: NCT00304382     History of Changes
Other Study ID Numbers: H-16562
Study First Received: March 16, 2006
Last Updated: February 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by VA Medical Center, Houston:
Pneumococcus
Pneumococcal pneumonia

Additional relevant MeSH terms:
Pneumococcal Infections
Pneumonia
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on April 23, 2014