Response to Pneumococcal-Polysaccharide Vaccine PPV23 in HIV-Positive Individuals

摘要

Streptococcus pneumoniae accounts for significant morbidity and mortality in individuals suffering from human immunodeficiency virus (HIV) infections. The Advisory Committee on Immunization Practices (ACIP) in the United States consequently recommended pneumococcal vaccination for HIV-positive individuals followed by a booster dose after 5 years. However, the benefits and ideal time for administration of pneumococcal vaccines have been controversial. Herein, we investigated the response to two vaccine serotypes, 14 and 23F post PPV23 immunization at the total, functional antibody and antigen-specific B cell levels. We did this in newly-diagnosed HIV-positive individuals who had not received highly active anti-retroviral therapy (HAART), as well as short and long-term HAART recipients, stratified based on their immune status as CD4 ≥ 200 cells/ mm3 or CD4 ≤ 200 cells/mm 3. In addition, receptors and cytokines speculated to be critical in pneumococcal polysaccharides (PPS) responses were elucidated and potential anomalies in their expression between HIV-positive and -negative adults were investigated.;Post immunization, both newly diagnosed and HAART experienced HIV-positive individuals showed increases in opsonophagocytic titers. This was concomitant with increases in PPS-specific IgM memory B cells, a critical B cell subset in pneumococcal defense. These findings indicate PPV23 vaccination to be beneficial. However, functional antibody and PPS-specific IgM memory B cell responses were significantly diminished in newly diagnosed and HAART experienced HIV-positive adults compared to HIV-negative individuals regardless of CD4 count and HAART status. These findings highlight damage to critical PPS-responding B cells early on during HIV-infection which fail to recover with long term HAART despite recovery in CD4+ T cells. Further, it emphasizes the need for alternate, robust vaccination approaches and evidence based vaccination strategies in high risk populations.;We next investigated molecular signals that may influence diminished PPV23 response noted in HIV-positive individuals. Inflammatory status of the host is associated inversely with T cell dependent (TD) vaccine response, but their influence on T cell independent antigens (TI-II) including PPS remains unknown. Although elevated in HIV-infected individuals, pro-inflammatory markers C-reactive protein (CRP), sCD27 and sCD30 did not correlate with PPV23 response indicating response to each vaccine is different and not always adversely influenced by generalized inflammatory status. Assessment of signals speculated to contribute towards PPS response revealed enhanced surface expression of tumor necrosis factor receptor transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) on PPS-specific B cells of HIV-positive and HIV-negative adults indicating a potential role for this receptor in pneumococcal defense. Although, surface TACI expression was similar between HIV-positive and -negative adults, soluble sTACI was significantly lower in HIV-positive adults. Diminished sTACI can potentially reduce responsiveness to its ligands and downstream Ig response. Improved understanding of these cytokines, receptors and downstream signaling will be useful while considering the design of new robust pneumococcal vaccines.