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

Abstract

BackgroundNewly 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.ObjectivesEvaluate 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.MethodsNewly 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.ResultsNewly 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.ConclusionsDespite 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.

Quantitative and Functional Antibody Responses to the 13-Valent Conjugate and/or 23-Valent Purified Polysaccharide Vaccine in Aging HIV-Infected Adults

“…Loss of memory B cell subsets is associated with impaired antibody responses to pneumococcal vaccination that are incompletely restored by ART [28–30]. We have previously shown that both ART-treated and -untreated HIV+ adults exhibit reduced serotype-specific IgM memory B cells after PPV compared to HIV− individuals [26,27]. In addition, a substantial proportion of patients on ART do not achieve normalization of CD4 counts [31].…”

“…Serotype-specific IgG and IgM serum levels were detected by enzyme-linked immunosorbent assay (ELISA) as previously described using 89SF or 007SP as standards. Opsonophagocytic killing assay (OPA) was performed as previously described [26,27] to determine functional antibody responses. Data were analyzed using the Opsotiter1 software program (University of Alabama at Birmingham).…”

Long‐term immune responses and comparative effectiveness of one or two doses of 7‐valent pneumococcal conjugate vaccine (PCV7) in HIV‐positive adults in the era of combination antiretroviral therapy

“…As the extent of immune recovery at 12 months was greater than at three or six months after cART, the capacity for ongoing reconstitution over time and subsequent effect thereof on immunogenicity and induced-immunological memory of PCV is implied [8]. The late effects of cART could also be inferred from the similar responses found for immunologically AIDS patients immunized immediately compared to those who had received cART for 6 to 12 months before vaccination [62]. The lack of benefit from delaying vaccination and our findings showing that baseline CD4 counts and PVL were not predictive of long-lasting immune responses support the current recommendations of vaccinating all individuals at the time of HIV diagnosis [12,14].…”

23-Valent Pneumococcal Polysaccharide Vaccine Uptake in the United States Air Force HIV Program

“…However, recent studies showed no significant improvement in laboratory markers of PPV23 response when immunization is delayed until after ART, and no correlation between viral load, postvaccination immunoglobulin G, and opsonophagocytic titers (OPT) was observed. 18,19 This is in contrast to hepatitis B virus (HBV) vaccine, where responsiveness, as measured by antibody to HBV surface antigen, has been shown to be 2-fold greater with use of ART in HIVinfected patients. 20 Despite high vaccine uptake for the first PPV23 dose, only 50% of eligible patients received the second PPV23 vaccination.…”