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
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1
Samia Akhtar
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1
Adam Finn
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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.
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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)