Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults☆
Introduction
Persons with human immunodeficiency virus (HIV) infection have high rates of pneumonia and bacteremia caused by Streptococcus pneumoniae [1], [2]. Pneumococcal infections often occur earlier in the course of HIV disease than do other opportunistic infections [1]. Such early manifestations of pneumococcal disease have been ascribed to various dysfunctions in the humoral and cellular immune system [1], [3]. Immune responses to the pneumococcal polysaccharide vaccine are inversely proportional to the degree of immunocompromise [4], [5], [6]. Therefore, the polysaccharide vaccine is recommended as early as possible during the course of HIV infection [7], [8].
HIV-infected persons may mount a more significant immune response to pneumococcal polysaccharides that are conjugated to protein antigens, thereby converting a T-cell independent immune response to a T-cell-dependent response. In HIV-infected adults, the conjugated Haemophilus influenzae type b (Hib) vaccine elicits a greater antibody response than the Hib polysaccharide vaccine [9]. However, in one published study of pneumococcal vaccination in HIV-infected adults, there was no significant improvement in the antibody concentration produced by one dose of pneumococcal conjugate vaccine compared with one dose of polysaccharide vaccine [10].
The goal of our study was to compare the qualitative and functional antibody responses to several regimens of the pneumococcal conjugate and polysaccharide vaccines in HIV-infected adults in a randomized, blinded, controlled trial.
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Study sites
HIV-infected adults were recruited from infectious disease clinics at the VA Greater Los Angeles Healthcare System, Los Angeles, California and Grady Health Systems, Atlanta, Georgia. Enrollment began January 1998 and continued through June 1999.
Persons >17 years old with HIV infection documented by enzyme-linked immunosorbent assay (ELISA) and Western Blot testing and with CD4 counts ≥200 cells/μl within the past 3 months were eligible. Persons with any of the following criteria were excluded:
Baseline demographics
The distribution of baseline demographic characteristics of the 67 patients who completed the study did not differ significantly among the study groups (Table 1). The pre-vaccination geometric mean antibody concentrations were similar for each study group (Table 2). The only serotype for which the pre-vaccination opsonophagocytic assay titers differed significantly between study groups was serotype 23F (Table 3). Subjects who did not complete the study (n=29) were more likely to be from the
Discussion
HIV-infected adults responded immunologically to both the pneumococcal conjugate and polysaccharide vaccines. However, the conjugate vaccine elicited higher antibody concentrations and greater functional antibody activity for several serotypes. No additional increases in antibody concentration or functional activity were elicited by a second dose of conjugate vaccine or a dose of polysaccharide vaccine given 8 weeks after the first dose of conjugate vaccine. The conjugate vaccine proved safe
Acknowledgements
We thank Brian Plikaytis and Elizabeth Zell for statistical input, Sally Shupien and Barbara Rossman for study management at the Los Angeles site, Ericka Patrick and Marie Todd-Turner for study management at the Atlanta site, Tajel Desai and Ian Lentnek for laboratory support, and John Walls for data entry. We would like to thank Wyeth-Lederle for donation of vaccines and provision of randomization codes. This study was supported financially by The Opportunistic Infections Research Program,
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- ☆
Presented in part at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Toronto, Canada, 17–20 September 2000 (abstract no. 48). Written informed consent was obtained from all study subjects in accordance with the Institutional Review Board guidelines of the Centers for Disease Control and Prevention, VA Greater Los Angeles Healthcare System, and Emory University.
- 1
Present address: Centers for Disease Control and Prevention, Arctic Investigations Program, 4055 Tudor Center Dr. Anchorage, AK 99508, USA.
- 2
Present address: National Center for Infectious Diseases, Centers for Disease Control and Prevention and Center for Health and Population Research, ICDDR,B, GPO Box 128, Dhaka 1000, Bangladesh.