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Inflammatory Markers and Immune Response to Pneumococcal Vaccination in HIV-Positive and -Negative Adults
Authors:Anita S Iyer  Noor M Khaskhely  David J Leggat  Jennifer A Ohtola  Jessica L Saul-McBeth  Sadik A Khuder  M A Julie Westerink
Institution:1. Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America;2. Department of Public Health, University of Toledo, 3000 Arlington Avenue, Toledo, Ohio 43614, United States of America;3. Department of Medicine; Department of Infectious Diseases and Department of Microbiology and Immunology, 135 Rutledge Avenue, Charleston, South Carolina 29425, United States of America;INSERM U1094, University of Limoges School of Medicine, FRANCE
Abstract:

Background

Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated.

Objective

To investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization.

Methods

Markers of inflammation, C-reactive protein (CRP), IL-6, sCD27 and sCD30, were assessed in HIV-positive and -negative individuals as potential predictors of PPV23 response. Serum levels of B cell activating factor (BAFF), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B cell maturation antigen (BCMA) and B cell expression of BAFF-R, TACI, BCMA, CD40 and CD21 were assessed in total (unselected) and PPS23F (antigen)-specific B cells of PPV23 immunized HIV-positive and -negative individuals.

Results

CRP, sCD27, sCD30 and BAFF were significantly elevated in the serum of HIV-positive individuals but did not adversely affect PPV23 response. Assessment of PPS-specific B cells revealed enhanced TACI and reduced BAFF-R expression compared to unselected B cells in HIV-positive and -negative individuals. Surface TACI was similar but soluble TACI was significantly lower in HIV-positive compared to HIV-negative individuals.

Conclusion

Current studies highlight a potential role for TACI in PPV23 response based on its enhanced expression on PPS-specific B cells. Although surface levels of TACI were similar, diminished soluble TACI (sTACI) in HIV-positive compared to HIV-negative individuals could potentially decrease BAFF responsiveness and Ig response. A better understanding of the role of TNF receptors could contribute to the design of improved pneumococcal vaccines.

Trial Registration

ClinicalTrials.gov NCT02515240
Keywords:
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