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Chapter 16 : Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children

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Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, Page 1 of 2

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Abstract:

Several investigational pneumococcal conjugate vaccines (PCVs) have been evaluated in phase II immunogenicity and reactogenicity studies with infants. PCVs prevent mucosal infections (acute otitis media [AOM] and colonization), and thus, some groups have also made efforts to characterize the mucosal immune response after vaccination in the hope of finding serological correlates of mucosal protection. High-avidity antibodies can have greater functional capacity than low-avidity antibodies, and the increase in avidity is regarded as a marker of the development of immunological memory. The South African follow-up study suggests that HIV-infected children would benefit from a booster immunization while non-HIV infected children may have persistent protection due to natural boosting via pneumococcal colonization or cross-reacting antigens. The geometric mean concentrations (GMCs) of antibodies against diphtheria toxoid were generally higher in the group given PCV7-CRM in studies with both wP (15)- and acellular pertussis protein (aP)-containing combinations. In a number of PCV7-CRM trials, the response to a primary series of doses of a diphtheria-tetanus-pertussis combination vaccine (DTP) alone has been compared to the response to DTP coadministered with PCV7-CRM. PCV11-D-T given to infants at 18 weeks of age was able to boost the diphtheria toxoid and TT responses of Filipino infants who had received a DTwP vaccine at 6, 10, and 14 weeks. In a study of PCV11-D-T, a formulation with aluminum hydroxide induced higher GMCs of antibodies, but differences were not statistically significant. In general, there were no significant differences in the avidities of antibodies.

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16

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Pneumococcal Conjugate Vaccine
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Meningococcal Conjugate Vaccine
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Acute Otitis Media
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Figure 1

GMCs of antibodies to vaccine serotypes reported in connection with the PCV efficacy trials with invasive pneumococcal disease and/or radiologically confirmed pneumonia as end points ( ).

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
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Image of Figure 2
Figure 2

Immunogenicities of 7- to 11-valent PCVs in Finnish infants after a primary series at 2, 4, and 6 months (A) and after the booster dose in the second year (B). GMCs are given for PCV7-CRM used previously ( ) and in the FinOM vaccine trial (unpublished data), for PCV7-OMPC used in the FinOM vaccine trial ( ), for PCV11-D-T with and without an aluminum adjuvant ( ), and for PCV11-PD ( ).

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
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Image of Figure 3
Figure 3

GMCs of antibodies after three primary doses of PCV7-CRM or PCV9-CRM in studies in the United Kingdom ( ), Germany ( ), Canada ( ), The Gambia ( ), South Africa ( ), the United States ( ), Finland (unpublished; reference ), and Iceland (unpublished; reference ). The PCV was given at 2, 3, and 4 months in the United Kingdom, Germany and The Gambia; at 2, 4, and 6 months in Canada, the United States and Finland; at 3, 4, and 5 months in Iceland; and at 6, 10, and 14 weeks in South Africa.

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
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Image of Figure 4
Figure 4

GMCs of antibodies after three primary doses of PCV11 with serotypes conjugated to diphtheria toxoid or TT in samples from children in the Philippines (immunized at 6, 10, and 14 weeks) and Israel and Finland (immunized at 2, 4, and 6 months) ( ). Serotypes 3, 6B, 14, and 18C were conjugated to diphtheria toxoid (D), and serotypes 1, 4, 5, 7F, 9V, 19F, and 23F were conjugated to tetanus protein (T).

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
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Figure 5

Kinetics of antibody responses to the adjuvant-containing PCV11-D-T in Filipino infants (Ph) ( ), to PCV7-CRM and PCV7-OMPC in Finnish infants (Fi) ( ), to PCV9-CRM in South African infants (SA) ( ), and to PCV7-CRM in U.S. infants ( ). The GMCs are given for serotypes 4, 6B, 14, and 23F before vaccination (pre) and after the first, second, and third doses (post 1, post 2, and post 3, respectively). The course of vaccination took place at 6, 10, and 14 weeks in the Philippines and at 2, 4, and 6 months in Finland and the United States.

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
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Tables

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Table 1

GMCs of antibodies to pneumococcal PSs of vaccine serotypes in samples from infants in efficacy trials with an end point of culture-confirmed AOM caused by the vaccine serotypes

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
Generic image for table
Table 2

Geometric means titers (GMT) of opsonophagocytic antibodies against pneumocci of the indicated serotypes in samples from infants in FinOM trials and POET with an end point of AOM caused by the vaccine serotypes

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
Generic image for table
Table 3

GMCs of antibodies to serotype 4, 6B, 14, and 23F pneumococcal PSs after primary series and booster doses in studies that have compared, directly or indirectly, schedules including two or three primary doses in early infancy with PCV boosting at 12 months of age

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16
Generic image for table
Table 4

Persistence of antibodies after immunization of South African, Czech, and Finnish infants with PCVs

Citation: Käyhty H, Lockhart S, Schuerman L. 2008. Immunogenicity and Reactogenicity of Pneumococcal Conjugate Vaccines in Infants and Children, p 227-243. In Siber G, Klugman K, Mäkelä P (ed), Pneumococcal Vaccines. ASM Press, Washington, DC. doi: 10.1128/9781555815820.ch16

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