Primary and Booster Salivary Antibody Responses to a 7-Valent Pneumococcal Conjugate Vaccine in Infants

Journal of Infectious Diseases, Oct 2000

Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P < .001). At age 13–14 months, there were marked increases in IgA (mean fold difference, 3.7–4.9) and IgG (mean fold difference, 4.1–11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.

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Primary and Booster Salivary Antibody Responses to a 7-Valent Pneumococcal Conjugate Vaccine in Infants

Sharon Choo (s.choo@sheffield 0 1 Qibo Zhang 0 1 Lynn Seymour 0 1 Samia Akhtar 0 1 Adam Finn 0 1 0 Received 20 April 2000; revised 12 June 2000; electronically published 31 August 2000. Presented in part: 37th annual meeting of the Infectious Diseases Society of America, Philadelphia, November 1999 (abstract 645); Second Interna- tional Symposium on Pneumococci and Pneumococcal Diseases , Sun City, South Africa, March 2000 (abstract P38). The study was approved by the South Sheffield local research ethics com- mittee. Written informed consent was obtained from the parent or guardian of each infant. Financial support: Wyeth-Lederle Vaccines and Pediatrics. Sheffield Children's Hospital , Sheffield S10 2TH , UK 1 Sheffield Institute for Vaccine Studies, Division of Child Health, University of Sheffield , Sheffield , United Kingdom Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P ! .001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4.1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants. - Streptococcus pneumoniae remains a major cause of invasive disease, pneumonia, and otitis media in young children. The incidence of antibiotic-resistant pneumococcal strains has been increasing, prompting the development of pneumococcal conjugate vaccines. These vaccines are immunogenic in infants [14], and 1 such vaccine (7VPnC; Wyeth-Lederle Vaccines, Pearl River, NY) has been shown to be effective in US infants [4]. Haemophilus influenzae type b (Hib) conjugate vaccines reduce Hib carriage in the nasopharynx [5] and induce IgA and IgG antibodies to Hib capsular polysaccharide in saliva [6]. Pneumococcal conjugate vaccines also reduce carriage of vaccine-type pneumococci [3, 7]. Local antibodies may play a role in the eradication of these organisms from upper respiratory tract mucosal surfaces. In the present study, we investigated primary and memory mucosal IgA and IgG antibody responses to a pneumococcal conjugate vaccine in UK infants primed with 7VPnC and boosted with a 23-valent pneumococcal plain polysaccharide vaccine (PPS). Methods Subjects. Healthy infants 610 weeks old were recruited from 1 UK center (Sheffield) as part of a 2-center randomized, controlled phase 2 immunogenicity trial. Serum data were collected from both sites, and salivary data were collected from Sheffield only. Immunizations. Infants were randomized to 1 of 3 groups and were immunized at ages 2, 3, and 4 months. Group 1 received diphtheria-tetanuswhole cell pertussis vaccine (DTwP; Evans Medical, Leatherhead, UK) and Hib CRM197 conjugate vaccine (HbOC; Wyeth-Lederle) as a single injection. Group 2 received DTwP/HbOC and 7VPnC as 2 separate injections, and group 3 received HbOC/7VPnC and DTwP as 2 separate injections. Group 1 received 7VPnC at ages 5, 6, and 7 months. All infants received a PPS booster at age 1316 months. 7VPnC contains 2 mg each of 4, 9V, 14, 18C, 19F, and 23F and 4 mg of 6B pneumococcal capsular saccharides conjugated to CRM197 protein. PPS contains 25 mg each of 23 pneumococcal polysaccharides, including the 7VPnC serotypes and serotypes 1 and 5. Saliva and blood samples. Saliva and blood samples were obtained before the first immunization, 39 weeks after the third immunization, before the booster immunization, and 39 weeks after the booster (ages 2, 5, 13, and 14 months). Unstimulated saliva samples were collected with a sponge swab, transported at 47C, and stored at 2707C until assay. Saliva samples were analyzed in blocks (serotypes 4, 6B, 18C, and 23F; serotypes 9V, 14, and 19F) in order of subject number, because the saliva quantities obtained from most infants were too small to assay for all serotypes. Secretory component (SC) antibodies to serotype 14 were measured in the 14-month samples of a randomly selected subset of subjects from groups 2 and 3 (n p 28). IgG and IgA anticapsular antibodies to serotypes 1 and 5 were measured in 13- and 14-month samples of another random subset of group 2 and group 3 infants (n p 68). Salivary assays were performed at the University of Sheffield, and serum assays were done at Wyeth-Lederle Laborato (...truncated)


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Sharon Choo, Qibo Zhang, Lynn Seymour, Samia Akhtar, Adam Finn. Primary and Booster Salivary Antibody Responses to a 7-Valent Pneumococcal Conjugate Vaccine in Infants, Journal of Infectious Diseases, 2000, pp. 1260-1263, 182/4, DOI: 10.1086/315834