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      Inhaled delivery of 23-valent pneumococcal polysaccharide vaccine does not result in enhanced pulmonary mucosal immunoglobulin responses

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          Abstract

          We compared the effect of intramuscular vs. inhaled 23-valent pneumococcal capsular polysaccharide vaccine (23-PPV) on pulmonary mucosal immunoglobulin levels. Bronchoalveolar lavage (BAL) and serum were collected from 33 adults before and 1 month after injected ( n = 16) or inhaled ( n = 17) 23-PPV. Levels of pneumococcal capsule-specific IgG and IgA to types 1, 9V and 14 were measured in each sample. Injected 23-PPV produced a significant increase in types 1, 9V and 14 capsule-specific IgG and type 1 IgA in both serum and BAL (type 1 geometric mean BAL IgG 9.8 ng/ml post-vaccine vs. 5 ng/ml pre-vaccine, p = 0.01; type 9V geo mean 5.6 ng/ml vs. 2.7 ng/ml, p = 0.001; type 14 geo mean 23.6 ng/ml vs. 6.2 ng/ml, p = 0.02). Inhaled vaccine produced no response in either BAL or serum.

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          The protective efficacy of polyvalent pneumococcal polysaccharide vaccine.

          Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccine's protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's vaccination history. Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.
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            The Significance of Pneumococcal Types.

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              CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization.

              Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4(+) T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8(+) T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4(+) T cells at the time of challenge.
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                Author and article information

                Journal
                Vaccine
                Vaccine
                Elsevier Science
                0264-410X
                1873-2518
                03 October 2008
                03 October 2008
                : 26
                : 42
                : 5400-5406
                Affiliations
                [a ]Pulmonary Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom
                [b ]Malawi-Liverpool-Wellcome Programme of Clinical Tropical Research, Universities of Malawi and Liverpool (UK), Queen Elizabeth Central Hospital, PO Box 30096, Chichiri, Blantyre, Malawi
                [c ]Department of Medicine, University of Malawi College of Medicine, PO Box 360, Blantyre, Malawi
                [d ]Department of Community Health Sciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW Calgary, Alberta T2N 4N1, Canada
                [e ]Karonga Prevention Programme, Chilumpha, Malawi and London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom
                Author notes
                [* ]Corresponding author at: Pulmonary Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom. Tel.: +44 151 705 3169; fax: +44 151 705 3370. sbgordon@ 123456liverpool.ac.uk
                Article
                JVAC8383
                10.1016/j.vaccine.2008.07.082
                2612086
                18708114
                75df2d14-9251-4468-a9ea-f90e8f1f5870
                © 2008 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 29 April 2008
                : 23 June 2008
                : 29 July 2008
                Categories
                Article

                Infectious disease & Microbiology
                polysaccharide,immunoglobulin,lung,mucosa,bronchoalveolar lavage,inhaled pneumococcal vaccine,pneumonia,streptococcus pneumoniae

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