Qualitative Change in Antibody Responses of Human Immunodeficiency Virus–Infected Individuals to Pneumococcal Capsular Polysaccharide Vaccination Associated with Highly Active Antiretroviral Therapy

Abstract

Variable region gene family 3 (V(H)3) is the predominant immunoglobulin (Ig) gene family used in human antibodies to pneumococcal capsular polysaccharide (PPS). This study examined whether highly active antiretroviral therapy (HAART) restores the ability of human immunodeficiency virus (HIV)-infected individuals to generate a V(H)3-positive response to PPS. The IgM, IgG, and V(H)3 (represented by antibodies expressing the determinant recognized by the monoclonal antibody D12) responses to PPS were determined for first-time recipients of a 23-valent PPS vaccine, both receiving and not receiving HAART, and second-time vaccine recipients receiving HAART. The results showed that only the individuals receiving HAART manifested a V(H)3-(D12)-positive response to PPS, despite a similar IgG response in each group. There was also a negative correlation between HIV load and PPS response for the groups receiving HAART. These findings suggest that HAART may influence qualitative aspects of the PPS response by restoring expression of certain V(H)3 genes used in the normal PPS response.

A 5‐year longitudinal follow‐up study of serological responses to 23‐valent pneumococcal polysaccharide vaccination among patients with HIV infection who received highly active antiretroviral therapy*

“…This finding is consistent with those of previous studies that also suggested a negative correlation between plasma HIV RNA load and serological responses to PPV that could be improved by HAART [27,36]. A recently published population-based cohort study to assess the effectiveness of 23-valent PPV also suggested that, irrespective of CD4 cell count at vaccination, vaccination provided no benefit when it was given to patients who had HIV RNA load 4100 000 copies/mL [12].…”

“…Studies investigating short-term serological responses to 23-valent PPV in HIV-infected patients have not produced consistent results [14][15][16][17][18][19][20][21][22][24][25][26][27][30][31][32][33][34][35][36][37][38], and only one study assessed the rate of antibody decline for five consecutive HAART, highly active antiretroviral therapy; MSM, men who have sex with men; PVL, plasma HIV RNA load; SD, standard deviation.…”

“…The discrepancy may result from enrolment of subjects with different degrees of immunosuppression, use of different vaccination schedules or vaccines (polysaccharide vs. conjugated vaccine) [22,24,37,38], receipt of different types of antiretroviral therapy (mono or dual antiretroviral therapy vs. HAART) [23,[25][26][27]36,38], different immunological or virological responses to HAART, and different durations of observation. In this study we used a single dose of 23-valent PPV and the overall response rate was estimated to be 50% for those patients with CD4 counts of !…”

“…Instead, most studies have assessed the responses to primary vaccination only among patients with CD4 counts of ! 200 cells/mL who were antiretroviralnaïve or were receiving HAART [26,27,[36][37][38]; or have compared the serological responses of patients with CD4 counts of o200 cells/mL at vaccination with those of patients with CD4 counts of ! 200 cells/mL at vaccination [23][24][25].…”

A Peptide Mimotope of Type 8 Pneumococcal Capsular Polysaccharide Induces a Protective Immune Response in Mice

“…Type-specific antibodies to pneumococcal polysaccharide are also restricted in their V-region gene use, being predominantly derived from members of the V H 3 immunoglobulin gene family (1,13,39). Although the importance of antibody restriction for pneumococcal resistance is unknown, it may translate into a poor response to polysaccharide-based vaccines in patients with IgG subclass deficiencies and/or dysregulation of V H 3 gene expression, such as human immunodeficiency virus-infected individuals (1,11,12,47).…”