Response to Pneumococcal Polysaccharide Vaccination in Newly Diagnosed HIV-Positive Individuals

Abstract

Background: Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible to Streptococcus pneumoniae infection compared to non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature of HIV infection. The specific nature of the immune cells involved in the production of protective antigen-specific antibodies in HIV-positive individuals remains to be elucidated.

Objectives: Evaluate the antibody and antigen-specific B cell response to the 23-valent pneumococcal polysaccharide vaccine in newly diagnosed HIV-positive patients. Moreover, determine if newly diagnosed patients with CD4<200 cells/μl benefit from 6-12 months of HAART, allowing partial viral suppression and immune reconstitution, prior to immunization.

Methods: Newly diagnosed HIV-positive patients with CD4>200 cells/μl and CD4<200 cells/μl were immunized with PPV23. Patients with CD4<200 cells/μl received either immediate or delayed immunization following 6-12 months of HAART. Antibody responses, opsonophagocytic activity and phenotypic analysis of pneumococcal polysaccharide-specific B cells were studied.

Results: Newly diagnosed HIV-positive patients demonstrated CD4-dependent increases in antibody and opsonophagocytic titers thought to be commensurate with protection. Functional opsonophagocytic titers of patients with CD4<200 cells/μl immunized immediately compared to patients with CD4<200 cells/μl receiving HAART for 6-12 months were not significantly different. Pneumococcal polysaccharide-specific B cells were distributed evenly between IgM memory and switched memory B cells for all groups, but IgM memory B cells were significantly lower than in HIV-negative individuals.

Conclusions: Despite CD4-dependent pneumococcal polysaccharide-specific deficiencies in newly diagnosed HIV-positive patients, vaccination was beneficial based on opsonophagocytic titers for all newly diagnosed HIV-positive groups. In HIV-positive patients with CD4<200 cells/μl, 6-12 months of HAART did not improve opsonophagocytic titers or antibody concentrations. Based on these findings, immunization with the 23-valent pneumococcal polysaccharide vaccine should not be delayed in newly diagnosed HIV-positive patients with CD4<200 cells/μl.

Keywords: Antigen-specific; B cell; HIV; Pneumococcus; Polysaccharide; Streptococcus pneumonia; Vaccine.

Figure 1. HIV-positive serum antibody and opsonophagocytic titers

HIV-positive volunteers were immunized with PPV23. Serum samples were obtained on days 0 and 30 post-immunization. Volunteers were classified according to CD4 count, <200 or >200 cells, and pre-vaccination HAART use. All samples were tested for PPS14 and PPS23F-specific IgG and IgM titers by ELISA expressed as μg/ml (n=43) (A–D) and functional activity by OPA expressed as opsonophagocytic titer (PPS14 n=42, PPS23F n=39) (E–F). Data are mean ± standard error of the mean. *p<0.05, **p<0.01, ***p<0.001.

Figure 2. PPS-specific B cells from HIV-positive individuals immunized with PPV23

HIV-positive donors were immunized with PPV23. On day 0 and day 7 post-immunization, lymphocyte enriched peripheral blood samples stained with fluorescently labeled PPS14 or PPS23F were evaluated by flow cytometry for distribution of CD27 and IgM among PPS-selected CD19+ B cells. Results for all HIV-positive individuals were categorized by CD4 counts and HAART usage. B cells were expressed as a percentage of total unselected or PPS-selected CD19+ B cells (A,B). B cells were expressed as the number of PPS-selected CD19+ B cells per ml (C,D). In each sample, 100,000 events were recorded. Data are mean ± standard error of the mean. *p<0.05, **p<0.01, ***p<0.001.

Figure 3. HIV-positive donors show significantly diminished response to PPV23 compared to HIV-negative donors

HIV-positive donor samples were compared to HIV-negative donor samples day 7 post-immunization with PPV23. Lymphocyte enriched peripheral blood samples stained with fluorescently labeled PPS14 or PPS23F were evaluated by flow cytometry for distribution of CD27 and IgM among PPS-selected CD19+ B cells. Post-immunization results for all HIV-positive individuals were categorized by CD4 counts and HAART usage. B cells were expressed as the number of PPS-selected CD19+ B cells per ml (A,B). In each sample, 100,000 events were recorded. Data are mean ± standard error of the mean. *p<0.05.