{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:46:28Z","timestamp":1793195188681,"version":"4.5.0"},"reference-count":27,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:sec><jats:title>Objectives.<\/jats:title><jats:p>To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM197 (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design.<\/jats:title><jats:p>Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Forty-five infants (34 SCD and 11 non-SCD) were vaccinated according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above .15 \u03bcg\/mL and 56% to 100% achieved antibody concentrations above 1.0 \u03bcg\/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above .15 \u03bcg\/mL in 53% to 92% by serotype and above 1.0 \u03bcg\/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>Infants with SCD respond to 7VPnC vaccine with antibody concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.106.5.965","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:50:41Z","timestamp":1092441041000},"page":"965-972","source":"Crossref","is-referenced-by-count":80,"title":["Safety and Immunogenicity of Heptavalent Pneumococcal Vaccine Conjugated to CRM197 Among Infants With Sickle Cell Disease"],"prefix":"10.1542","volume":"106","author":[{"given":"Katherine L.","family":"O'Brien","sequence":"first","affiliation":[{"name":"From the Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland;"},{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Swift","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry A.","family":"Winkelstein","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathuram","family":"Santosham","sequence":"additional","affiliation":[{"name":"From the Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland;"},{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Stover","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Luddy","sequence":"additional","affiliation":[{"name":"Sinai Hospital, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Gootenberg","sequence":"additional","affiliation":[{"name":"Georgetown University School of Medicine, Washington, DC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey T.","family":"Nold","sequence":"additional","affiliation":[{"name":"Pediatric Center of Annapolis, Annapolis, Maryland; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Eskenazi","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine, Department of Pediatrics, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally J.","family":"Snader","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard M.","family":"Lederman","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Department of Pediatrics, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Pneumococcal Conjugate Vaccine Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"2021121003315572200_B1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1056\/NEJM198606193142501","article-title":"Prophylaxis with oral penicillin in children with sickle cell anemia.","volume":"314","author":"Gaston","year":"1986","journal-title":"N Engl J Med"},{"key":"2021121003315572200_B2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/ajh.2830390305","article-title":"Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty year epidemiologic experience.","volume":"39","author":"Wong","year":"1992","journal-title":"Am J Hematol"},{"key":"2021121003315572200_B3","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1093\/clinids\/14.5.1124","article-title":"Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis and vaccination.","volume":"14","author":"Wong","year":"1992","journal-title":"Clin Infect Dis"},{"key":"2021121003315572200_B4","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1542\/peds.84.3.500","article-title":"Mortality in children and adolescents with sickle cell disease.","volume":"84","author":"Leikin","year":"1989","journal-title":"Pediatrics"},{"key":"2021121003315572200_B5","first-page":"169","article-title":"Mortality among children with sickle cell disease identified by newborn screening during 1990\u20131994\u2014California, Illinois, and New York.","volume":"47","author":"Centers for Disease Control and Prevention","year":"1998","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2021121003315572200_B6","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.2105\/AJPH.87.8.1317","article-title":"National trends in mortality of children with sickle cell disease, 1968 through 1992.","volume":"87","author":"Davis","year":"1997","journal-title":"Am J Public Health"},{"key":"2021121003315572200_B7","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0022-3476(05)80036-8","article-title":"Experience with the use of prophylactic penicillin in children with sickle cell anemia.","volume":"118","author":"Pegelow","year":"1991","journal-title":"J Pediatr"},{"key":"2021121003315572200_B8"},{"key":"2021121003315572200_B9","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1056\/NEJM196910232811703","article-title":"Functional asplenia in sickle-cell anemia.","volume":"281","author":"Pearson","year":"1969","journal-title":"N Engl J Med"},{"key":"2021121003315572200_B10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJM196808292790904","article-title":"Deficiency of pneumococcal serum opsonizing activity in sickle-cell disease.","volume":"279","author":"Winkelstein","year":"1968","journal-title":"N Engl J Med"},{"key":"2021121003315572200_B11","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1056\/NEJM197304192881601","article-title":"An abnormality of the alternate pathway of complement activation in sickle-cell disease.","volume":"288","author":"Johnston","year":"1973","journal-title":"N Engl J Med"},{"key":"2021121003315572200_B12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0022-3476(77)81357-7","article-title":"Pneumococcal infections in sickle cell disease.","volume":"91","author":"Winkelstein","year":"1977","journal-title":"J Pediatr"},{"key":"2021121003315572200_B13","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/infdis\/126.5.507","article-title":"Increased susceptibility of splenectomized rats to infection with Diplococcus pneumoniae.","volume":"126","author":"Levine","year":"1972","journal-title":"J Infect Dis"},{"key":"2021121003315572200_B14","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1056\/NEJM197710272971701","article-title":"Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy.","volume":"297","author":"Ammann","year":"1977","journal-title":"N Engl J Med"},{"key":"2021121003315572200_B15","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0022-3476(98)70235-5","article-title":"Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease.","volume":"133","author":"Vernacchio","year":"1998","journal-title":"J Pediatr"},{"key":"2021121003315572200_B16","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1542\/peds.101.4.604","article-title":"Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 in United States infants.","volume":"101","author":"Rennels","year":"1998","journal-title":"Pediatrics"},{"key":"2021121003315572200_B17"},{"key":"2021121003315572200_B18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/00006454-198706000-00006","article-title":"Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination.","volume":"6","author":"Koskela","year":"1987","journal-title":"Pediatr Infect Dis J"},{"key":"2021121003315572200_B19","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/cdli.2.5.590-597.1995","article-title":"Assignment of weight-based antibody units to a human antipneumococcal standard reference serum, lot 89-S.","volume":"2","author":"Quartaert","year":"1995","journal-title":"Clin Diagn Lab Immunol"},{"key":"2021121003315572200_B20"},{"key":"2021121003315572200_B21","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1128\/CDLI.7.5.788-793.2000","article-title":"Serum opsonic activity in infants with sickle cell disease immunized with pneumococcal polysaccharide protein-conjugate vaccine.","volume":"7","author":"Nowak-Wegrzyn","year":"2000","journal-title":"Clin Diag Lab Immunol"},{"key":"2021121003315572200_B22","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S0022-3476(05)82209-7","article-title":"Serologic follow-up of children with sickle cell disease immunized with a Haemophilus influenzae type b conjugate vaccine during early infancy.","volume":"118","author":"Gigliotti","year":"1991","journal-title":"J Pediatr"},{"key":"2021121003315572200_B23","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S0022-3476(89)80451-2","article-title":"Immunization of young infants with sickle cell disease with a Haemophilus influenzae type b saccharide-diphtheria CRM197 protein conjugate vaccine.","volume":"114","author":"Gigliotti","year":"1989","journal-title":"J Pediatr"},{"key":"2021121003315572200_B24","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1542\/peds.82.4.571","article-title":"Haemophilus influenzae type b immunization of children with sickle cell disease.","volume":"82","author":"Frank","year":"1988","journal-title":"Pediatrics"},{"key":"2021121003315572200_B25","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1172\/JCI112824","article-title":"Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative pathway in sickle cell disease is related to antibody deficiency.","volume":"79","author":"Bjornson","year":"1987","journal-title":"J Clin Invest"},{"key":"2021121003315572200_B26","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/infdis\/154.5.760","article-title":"Lack of a requirement for the Fc region of IgG in restoring pneumococcal opsonization via the alternative complement pathway in sickle cell disease.","volume":"154","author":"Bjornson","year":"1986","journal-title":"J Infect Dis"},{"key":"2021121003315572200_B27","first-page":"37","article-title":"Complement and immunoglobulin levels in early childhood in homozygous sickle cell disease.","volume":"21","author":"De Ceulaer","year":"1986","journal-title":"J Clin Lab Immunol"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/106\/5\/965\/842214\/965.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/106\/5\/965\/842214\/965.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T05:31:33Z","timestamp":1682746293000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/106\/5\/965\/63213\/Safety-and-Immunogenicity-of-Heptavalent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,1]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2000,11,1]]},"published-print":{"date-parts":[[2000,11,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.106.5.965","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[2000,11,1]]}}}