David J Leggat, Anita S Iyer, Jennifer A Ohtola, Sneha Kommoori, Joan M Duggan, Claudiu A Georgescu, Sadik A Khuder, Noor M Khaskhely and MA Julie Westerink
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 polysaccharidespecific 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.
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