Avidity Maturation of Antibody to<i>Haemophilus influenzae</i>Type b (Hib) after Immunization with Diphtheria‐Tetanus–Acellular Pertussis–Hib–Hepatitis B Combined Vaccine in Infants

Pichichero, Michael E.; Voloshen, Timothy; Zajac, Diane; Passador, Sherry

doi:10.1086/314989

Cited by 41 publications

(21 citation statements)

References 13 publications

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“…By examining avidity maturation following a 10-g booster dose of meningococcal polysaccharide, we have demonstrated that vaccinated individuals with SBA titers above and below 128 display similar avidity maturation in their antibody response and by this criterion should therefore have immunological memory established. Data now exist which demonstrate the increase in avidity over time following priming of infants or toddlers with Hib (18,30), Streptococcus pneumoniae (3), and Neisseria meningitidis serogroup C conjugate vaccines (31). Such data have been generated in the context of boosters of low doses of plain polysaccharide or conjugate vaccine in young infants and are now accepted as indicative that a T-celldependent response has been generated.…”

Section: Discussionmentioning

confidence: 99%

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Borrow

Andrews²,

Miller³

2001

Infect Immun

297

194

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The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of >4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of >8 showed that for 93% (27 of 29) the titer was >4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or >128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of >128 had hSBA titers of >4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of >4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre-and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result >4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of >128 after a 10-g polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-g dose. Furthermore, the increase in geometric mean avidity index pre-and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.

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Section: Discussionmentioning

confidence: 99%

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Borrow

Andrews²,

Miller³

2001

Infect Immun

297

194

View full text Add to dashboard Cite

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“…Hence, a critical point with regard to the extension of early life immunization strategies is to ensure the quality of induced responses and the duration of protection. Recently, it has been demonstrated that infant immunization with conjugated polysaccharide vaccines can generate antibodies with a progressive avidity increase [26][27][28][29][30]. However, these studies do not allow the comparison of infant data with those obtained following the immunization of older children or adults, because the latter are already naturally primed by carriage or exposure to cross-reacting polysaccharides prior to vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…Studies performed in infants indicated a progressive increase of somatic mutation of immunoglobulin genes between 2 and 10 months of age, with evidence for selection only observed from 6 months onwards [24,25]. Avidity maturation was shown to occur following early infant immunization with conjugated polysaccharide vaccines [26][27][28][29][30]. However, it has been reported that following N. meningitidis infection, infants produced specific antibodies of a significantly lower average avidity than older children, which correlated with the absence of bactericidal activity in infant sera [31].…”

Section: Introductionmentioning

confidence: 99%

Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines

Schallert¹,

Pihlgren²,

Kovařík³

et al. 2002

Eur. J. Immunol.

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“…In addition to measuring antibody responses, avidity maturation (which is characteristic of a T-celldependent antibody response) can be assessed after immunization with polysaccharide conjugate vaccines and then used as a surrogate marker for the induction of immune memory. The use of avidity indices (AIs) in this way has now been widely documented for MCC (4,19,20), Haemophilus influenzae type b (Hib) conjugate (9,16), and pneumococcal conjugate (2) vaccines.…”

mentioning

confidence: 99%

Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom

Borrow

Green

Finn³

et al. 2003

Infect Immun

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It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one-or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n ‫؍‬ 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of >8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of >8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.In November 1999, the United Kingdom introduced universal meningococcal C conjugate (MCC) vaccination at 2, 3, and 4 months of age, on the basis of safety and immunogenicity studies (15). A prelicensure study in 83 infants in the United Kingdom (18) who were given one of the three candidate MCC vaccines, a tetanus toxoid conjugate (MCC-TT) (14), at 2, 3, and 4 months of age demonstrated that the vaccine was highly immunogenic after a single dose at 2 months of age, with all infants achieving a putative protective antibody titer of Ն8 (bactericidal antibody levels in serum were measured with baby rabbit complement [rSBA]) (1a, 3). There was a further significant increase in antibody levels after a second dose of MCC-TT vaccine but no further increase after the third dose at 4 months of age. Antibody levels fell by 14 months of age, but booster antibody responses to meningococcal C polysaccharide and MCC vaccines provided evidence of successful priming for immunologic memory after the full course of three doses (18).The excellent response to this MCC-TT vaccine among infants at 2 months of age and the modest response to the third dose of vaccine raise the possibility that a one-or two-dose schedule in infants may be sufficient to provide protection from meningococcal C disease. Demonstration of priming for immune memory by the one-or two-dose schedules suggests that these regims could also provide long-term protection. This could be assessed by examining antibody responses to meningococcal C polysaccharide vaccination in the second year of life since children do not normally respond to polysaccharide ...

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Avidity Maturation of Antibody toHaemophilus influenzaeType b (Hib) after Immunization with Diphtheria‐Tetanus–Acellular Pertussis–Hib–Hepatitis B Combined Vaccine in Infants

Cited by 41 publications

References 13 publications

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Generation of adult-like antibody avidity profiles after early-life immunization with protein vaccines

Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom

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