Ability of 3 Different Meningococcal C Conjugate Vaccines to Induce Immunologic Memory after a Single Dose in UK Toddlers

Richmond, Peter; Borrow, Ray; Green, David; Findlow, Jamie; Martin, Sarah; Morris, Rhonwen; Cartwright, Keith; Miller, Elizabeth

doi:10.1086/317646

Cited by 204 publications

(141 citation statements)

References 16 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Moreover these conjugate vaccines will induce a memory response with a rise of antibody titer after several rounds of Table 1 Box 1 immunization and a booster response several months later . Surprisingly, in older infants and in adults, the same conjugate vaccine [21][22][23][24] does not induce a memory response but a response similar to the one obtained with the plain CPS preparation , even though the [25][26][27][28] response to the conjugate appears in some cases more robust . We have shown that humans display a circulating marginal zone B cell population which is involved in TI response and which diversifies its Ig receptor in the absence of cognate T-B interactions.…”

Section: Paradoxmentioning

confidence: 99%

Vaccination against encapsulated bacteria in humans: paradoxes

Weller

Reynaud

Weill

2005

Trends in Immunology

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Infection with encapsulated bacteria can be prevented by vaccination with capsular polysaccharides, either plain or conjugated to a protein carrier. But results concerning these vaccinations raise several paradoxes. Polysaccharides from encapsulated bacteria are generally considered to be Tindependent antigens unable to trigger a T-dependent germinal center reaction, but strikingly, anti-polysaccharide antibodies are often mutated in humans. Polysaccharide-protein conjugate vaccines are able to induce a true T-dependent memory response with a rise in antibody titers and a switch to high affinity-IgG antibodies in children below 2 years of age, but neither the plain nor the conjugate vaccine can induce memory in older infants and adults. We propose some explanations to these paradoxes based on our recent observation that humans display a circulating splenic marginal zone B cell population with a pre-diversified immunoglobulin repertoire in charge of the immune response to T-independent vaccines. The impact of diseases generated by encapsulated bacteria has been underlined in many contexts and it is estimated that they are responsible for millions of children s deaths each year . Nevertheless, when looking at the abundant literature on immune responses to ' [1] encapsulated bacteria after vaccination by either plain or conjugated capsular polysaccharide vaccines, some paradoxes emerge which we would like to discuss. MESH Keywords Paradox 1It is generally accepted that bacterial capsular polysaccharides (CPS) are TI antigens that trigger specific B cells residing in the splenic marginal zone to secrete antibodies with opsonophagocytic properties against these bacteria . In rodents in which these responses have [2] been mostly studied, immunization do not induce an extensive proliferation within B cell follicles, neither the formation of germinal centers, and are for most of them taken care by unmutated germline antibodies . In humans on the contrary, the splenic marginal zone [3][4][5] contains B cells with mutated Ig receptors and mutated antibodies are raised in responses to encapsulated bacteria, these mutations [6][7][8] being responsible for the antibodies avidity for the immunizing antigen , . In all species, these TI responses do not trigger any [9 10] memory, the B cells engaged being able very rapidly to switch isotype and to secrete large amount of antibodies. These plasma cells can remain in the organism for various lengths of time, after which the response wanes out , . To account for the presence in humans of [11 12] mutated antibodies during a T-independent immune response that cannot normally trigger a cognate T-B dependent germinal center reaction, the classical explanation put forward by authors is that such responses are in fact taken care by memory B cells that bona fide have been primed by a previous encounter with the pathogen, either during an infection or by silent carriage . These memory B [13][14][15] cells would then eventually reside in the splenic marginal zone where they ...

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“…Following promising results in infants vaccinated under the UK 2/3/4 month schedule [11][12][13], the DH initiated further clinical trials to answer key policy-related questions. These trials determined the schedule to be used for catch-up immunisation of older age groups [14], the effect of prior vaccination with plain meningococcal C polysaccharide used for outbreak control on the response to MCC vaccines [15][16][17], and the compatibility of MCC vaccines when given at the same time as other vaccines used in the UK schedule, in particular diphtheria and tetanus vaccines which are similar to the carrier proteins in the MCC vaccines [1]. These DH-funded trials were complemented by manufacturer-sponsored trials designed to provide data required by the licensing authority, such as batch-tobatch variation [18] and the safety and immunogenicity of MCC vaccines compared with the licensed plain polysaccharide vaccine [19].…”

Section: Pre-licensure Studiesmentioning

confidence: 99%