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Antibody to Capsular Polysaccharides of Streptococcus pneumoniae after Vaccination of Human Immunodeficiency Virus-Infected Subjects with 23Valent Pneumococcal Vaccine Maria C. Rodriguez-Barradas, Daniel M. Musher, Christopher Lahart, Christine Lacke, Jean Groover, David Watson, Robert Baughn, Thomas Cate, and Gordon Crofoot
Medical Service (Infectious Disease and Special Medicine Sections), Veterans Affairs Medical Center. Harris County Hospital District (Thomas Street Clinic), Memorial Southwest Medical Center. and Departments of Medicine and Microbiology/Immunology, Baylor College ofMedicine. Houston. Texas
Infection with human immunodeficiency virus (HIV) was initially recognized by its capacity to reduce cellular immune function and increase susceptibility to opportunistic infections. Soon thereafter, HIV infection was also found to be associated with impaired humoral responses [1]; abnormalities ofB cell function include decreased responses to T celldependent antigens such as diphtheria and tetanus toxoids, influenza and hepatitis virus vaccines, pokeweed mitogen, and T cell-independent pneumococcal polysaccharide antigen [1-8]. Clinical and epidemiologic studies have shown that HI Vinfected individuals are more susceptible to infections associated with an impaired humoral response, especially those caused by common bacterial pathogens such as Streptococcus pneumoniae and Haemophilus infiuenzae [9, 10]. The frequency of unusual pneumococcal infections may also be increased [8]. The recent estimate [10] that pneumococcal bacteremia occurs in 9.4 of 1000 AIDS patients/year suggests a several hundred-fold increase over the incidence in an agematched, non-HIV-infected population. Because of this in-
Received 19 August 1991; revised 14 October 1991. Financial support: Merit Review Funding, Department of Veterans Affairs; fellowship grant from Fundacion Mariscal de Ayacucho (M.C.R.-B.). Reprints or correspondence: Dr. Maria C. Rodriguez-Barradas, Room 4B-370, Infectious Disease Section, Veterans Affairs Medical Center, Houston, TX 77030. The Journal of Infectious Diseases 1992;165:553-6 © ) 992 by The University of Chicago. All rights reserved. 0022-1899/92/6503-0023$01.00
creased susceptibility to pneumococcal infection, the Centers for Disease Control (CDC) currently recommends that all HIV -infected subjects be given 23-valent pneumococcal polysaccharide vaccine. Studies in which Hlv-infected persons have been immunized with pneumococcal polysaccharide have generally shown that responses are diminished [1-6], although some results are difficult to compare because of differences in the study populations and in the methods used to measure antibody levels. The principal methodologic problem is that previous assays have not distinguished between antibody to cell wall and antibody to capsular polysaccharides [11, 12]. Pneumococcal vaccine contains substantial contamination by cell wall polysaccharides (CWPS); antibody to CWPS, which is ubiquitous in the normal population, increases after vaccination. Pneumococcal capsular polysaccharides (PPS) that are dispensed by the American Type Culture Collection for use as antigens are made as part ofvaccine preparation by Merck Sharp & Dohme and are also contaminated with CWPS. Unless steps are taken to remove antibody to CWPS, for example by adsorbing sera before the assay with cell wall antigen, assays will measure antibody both to capsular and cell wall components without distinguishing between them [11, 12]. As we discussed in a recent review [13], the protective effect of anti-CWPS IgG in humans is, at best, questionable. In the present study, our objective was to use an ELISA with appropriate adsorption in order to quantitate IgG antibody reactive with PPS after vaccination of HIV-infected
Downloaded from http://jid.oxfordjournals.org/ at University of Illinois at Urbana-Champaign on September 8, 2015
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 ~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%) of60 in 12 HIV-infected subjects with >500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P < .001). Subjects with ~500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with >500 CD4 cells and controls, respectively (P < .001). There were no differences between responses in those with
Antibody to Capsular Polysaccharides of Streptococcus pneumoniae after Vaccination of Human Immunodeficiency Virus-Infected Subjects with 23Valent Pneumococcal Vaccine Maria C. Rodriguez-Barradas, Daniel M. Musher, Christopher Lahart, Christine Lacke, Jean Groover, David Watson, Robert Baughn, Thomas Cate, and Gordon Crofoot
Medical Service (Infectious Disease and Special Medicine Sections), Veterans Affairs Medical Center. Harris County Hospital District (Thomas Street Clinic), Memorial Southwest Medical Center. and Departments of Medicine and Microbiology/Immunology, Baylor College ofMedicine. Houston. Texas
Infection with human immunodeficiency virus (HIV) was initially recognized by its capacity to reduce cellular immune function and increase susceptibility to opportunistic infections. Soon thereafter, HIV infection was also found to be associated with impaired humoral responses [1]; abnormalities ofB cell function include decreased responses to T celldependent antigens such as diphtheria and tetanus toxoids, influenza and hepatitis virus vaccines, pokeweed mitogen, and T cell-independent pneumococcal polysaccharide antigen [1-8]. Clinical and epidemiologic studies have shown that HI Vinfected individuals are more susceptible to infections associated with an impaired humoral response, especially those caused by common bacterial pathogens such as Streptococcus pneumoniae and Haemophilus infiuenzae [9, 10]. The frequency of unusual pneumococcal infections may also be increased [8]. The recent estimate [10] that pneumococcal bacteremia occurs in 9.4 of 1000 AIDS patients/year suggests a several hundred-fold increase over the incidence in an agematched, non-HIV-infected population. Because of this in-
Received 19 August 1991; revised 14 October 1991. Financial support: Merit Review Funding, Department of Veterans Affairs; fellowship grant from Fundacion Mariscal de Ayacucho (M.C.R.-B.). Reprints or correspondence: Dr. Maria C. Rodriguez-Barradas, Room 4B-370, Infectious Disease Section, Veterans Affairs Medical Center, Houston, TX 77030. The Journal of Infectious Diseases 1992;165:553-6 © ) 992 by The University of Chicago. All rights reserved. 0022-1899/92/6503-0023$01.00
creased susceptibility to pneumococcal infection, the Centers for Disease Control (CDC) currently recommends that all HIV -infected subjects be given 23-valent pneumococcal polysaccharide vaccine. Studies in which Hlv-infected persons have been immunized with pneumococcal polysaccharide have generally shown that responses are diminished [1-6], although some results are difficult to compare because of differences in the study populations and in the methods used to measure antibody levels. The principal methodologic problem is that previous assays have not distinguished between antibody to cell wall and antibody to capsular polysaccharides [11, 12]. Pneumococcal vaccine contains substantial contamination by cell wall polysaccharides (CWPS); antibody to CWPS, which is ubiquitous in the normal population, increases after vaccination. Pneumococcal capsular polysaccharides (PPS) that are dispensed by the American Type Culture Collection for use as antigens are made as part ofvaccine preparation by Merck Sharp & Dohme and are also contaminated with CWPS. Unless steps are taken to remove antibody to CWPS, for example by adsorbing sera before the assay with cell wall antigen, assays will measure antibody both to capsular and cell wall components without distinguishing between them [11, 12]. As we discussed in a recent review [13], the protective effect of anti-CWPS IgG in humans is, at best, questionable. In the present study, our objective was to use an ELISA with appropriate adsorption in order to quantitate IgG antibody reactive with PPS after vaccination of HIV-infected
Downloaded from http://jid.oxfordjournals.org/ at University of Illinois at Urbana-Champaign on September 8, 2015
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 ~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%) of60 in 12 HIV-infected subjects with >500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P < .001). Subjects with ~500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with >500 CD4 cells and controls, respectively (P < .001). There were no differences between responses in those with
