Antibody to Capsular Polysaccharides of Streptococcus pneumoniae after Vaccination of Human Immunodeficiency Virus-Infected Subjects with 23-Valent Pneumococcal Vaccine

Abstract

The Centers for Disease Control recommends that, because of a greatly increased susceptibility to pneumococcal infection, all persons infected with human immunodeficiency virus (HIV) receive pneumococcal vaccine. Using an ELISA specific for antibody to capsular polysaccharide, a postvaccination antibody was evaluated to five commonly infecting serotypes of Streptococcus pneumoniae. Thirty-nine HIV-infected persons with less than or equal to 500 CD4 cells exhibited significantly fewer responses than did healthy controls; overall, only 46 (24%) of 195 possible responses were positive compared with 45 (75%) of 60 in 12 HIV-infected subjects with greater than 500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P less than .001). Subjects with less than or equal to 500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with greater than 500 CD4 cells and controls, respectively (P less than .001). There were no differences between responses in those with less than 200 and those with 200-500 CD4 cells. Within groups stratified by CD4 cell counts, further stratification by clinical status did not reveal significant differences. Since asymptomatic HIV-infected persons with less than 500 CD4 cells show abnormal responses, pneumococcal vaccine should be given when HIV infection is first detected.

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*

“…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.…”

“…200 cells/mL after receipt of HAART and for those patients who have undergone pneumococcal polysaccharide vaccination 5 years earlier [13]. However, most studies conducted in patients not receiving HAART suggest that HIV-infected patients have a significantly lower frequency and magnitude of antibody response to vaccination with 23-valent PPV than those without HIV infection, and antibody titres [immunoglobulin G (IgG) or IgM] appear to be associated with CD4 cell count and decrease more rapidly in HIV-infected patients [14][15][16][17][18][19][20][21][22]. Interpretation of studies conducted in the HAART era is limited by different durations of and immunological and virological responses to HAART, different vaccination schedules and short-term observation of antibody responses [23][24][25][26][27].…”

Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children

“…Furthermore, to evaluate positive responses to pneumococcal polysaccharide vaccine (PPV) the use of arbitrary levels is less accurate than comparing fold increase from baseline (39) and the presence of opsonizing antibodies should be considered. Finally, post vaccination pneumococcal IgG levels seem to be reduced in treatment naïve and HAART-treated HIV-1-infected patients (40,41). The mechanisms underlying this condition are poorly known.…”

A new endpoint definition improved clinical relevance and statistical power in a vaccine trial

“…The immunogenicity evaluation of such vaccines must take into account the response to any serotype, all of them participating in the definition of the primary endpoint. In general, the comparison between groups involves the distribution of serotype specific antibody concentrations for each serotype using geometric means [3,4,5,6,7,8,9]. The P-value is then adjusted for Bonferroni or Family Discovery Rate (FDR)-controlling methods [1,10].…”