Elsevier

Vaccine

Volume 20, Issues 3–4, 12 November 2001, Pages 545-553
Vaccine

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

https://doi.org/10.1016/S0264-410X(01)00347-4Get rights and content

Abstract

In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with ≥200 CD4 cells/μl received placebo (PL), 7-valent conjugate, or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate–conjugate, conjugate–polysaccharide, placebo–polysaccharide, placebo–placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders, when compared with persons receiving placebo–polysaccharide, persons receiving conjugate–conjugate and conjugate–polysaccharide had higher antibody concentrations (serotypes 4, 6B, 9V and serotype 23F, respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V, respectively) after the second dose (P<0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses.

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.

Section snippets

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,

References (33)

  • R.T. Coughlin et al.

    Characterization of pneumococcal specific antibodies in healthy unvaccinated adults

    Vaccine

    (1998)
  • E.N. Janoff et al.

    Pneumococcal disease during HIV infection: epidemiologic, clinical and immunologic perspectives

    Ann. Int. Med.

    (1992)
  • Redd SC, Rutherford GW III, Sande MA, et al. The role of human immunodeficiency virus in pneumococcal bacteremia in San...
  • A.J. Pinching

    Antibody responses in HIV infection

    Clin. Exp. Immunol.

    (1991)
  • J.B. Glaser et al.

    Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex

    J. Infect. Dis.

    (1991)
  • P.J. Weiss et al.

    Response of recent human immunodeficiency virus seroconverters to the pneumococcal polysaccharide vaccine and Haemophilus influenzae type b conjugate vaccine

    J. Infect. Dis.

    (1995)
  • Rodriquez-Barradas MC, Musher DM, Lahart C, et al. Antibody to capsular polysaccharides of Streptococcus pneumoniae...
  • Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory...
  • Centers for Disease Control and Prevention. 1997 USPHS/IDSA Guidelines for prevention of opportunistic infections in...
  • Steinhoff MC, Auerbach BS, Nelson KE, et al. Antibody responses to Haemophilus influenzae type b vaccines in men with...
  • F. Ahmed et al.

    Effect of human immunodeficiency virus type 1 infection on the antibody response to a glycoprotein conjugate pneumococcal vaccine: results from a randomized trial

    J. Infect. Dis.

    (1996)
  • Plikaytis BD, Goldblatt D, Frasch CE, et al. An analytical model applied to a multicenter pneumococcal enzyme-linked...
  • N.F. Concepcion et al.

    Pneumococcal type 22F polysaccharide absorption improves the specificity of pneumococcal polysaccharide enzyme-linked immunosorbent assay

    Clin. Diag. Lab. Immunol.

    (2001)
  • Plikaytis BD, Holder PF, Carlone GM. Program ELISA for Windows user’s manual, version 1.00. Atlanta, GA, Centers for...
  • Quataert SA, Kirch CS, Quackenbush LJ, et al. Assignment of weight-based antibody units to a human antipneumococcal...
  • Romero-Steiner S, Libutti D, Pais LB, et al. Standardization of an opsonophagocytic assay for the measurement of...
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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.

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