Secondary IgG responses to type 3 pneumococcal polysaccharide III. T cell requirement for development of B memory

Braley‐Mullen, Helen

doi:10.1002/eji.1830071106

Cited by 32 publications

(27 citation statements)

References 29 publications

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“…Although it is well established that Th1 effector CD4ϩ T cells are required for the control of parasitemia early in primary P. c. chabaudi infection (19), these data suggest that inflammatory CD4 ϩ T-cell responses are unlikely to contribute significantly to protection against repeat infection. In contrast, antibody boosting during challenge in patently infected mice (results not shown) suggested that antibody responses were preserved, consistent with the reduced requirements for CD4ϩ T-cell help during secondary antibody responses (1,35).…”

Section: Discussionmentioning

confidence: 60%

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

2005

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We examined immunity induced by subpatent blood-stage malaria (undetectable by microscopy) using the rodent malaria parasite, Plasmodium chabaudi chabaudi, postulating that limited infection may allow expansion of antigen-specific T cells that are normally deleted by apoptosis. After three infections drug cured at 48 h, mice were protected against high-dose challenge with homologous or heterologous parasites (different strain or variant). Immunity differed from that generated by three untreated, patent infections. Subpatently infected mice lacked immunoglobulin G (IgG) to variant surface antigens, despite producing similar titers of total malaria-specific IgG to those produced by patently infected mice, including antibodies specific for merozoite surface antigens conserved between heterologous strains. Antigen-specific proliferation of splenocytes harvested prechallenge was significantly higher in subpatently infected mice than in patently infected or naive mice. In subpatently infected mice, lymphoproliferation was similar in response to homologous and heterologous parasites, suggesting that antigenic targets of cell-mediated immunity were conserved. A Th1 cytokine response was evident during challenge. Apoptosis of CD4؉ and CD8 ؉ splenic lymphocytes occurred during patent but not subpatent infection, suggesting a reason for the relative prominence of cell-mediated immunity after subpatent infection. In conclusion, subpatent infection with blood stage malaria parasites induced protective immunity, which differed from that induced by patent infection and targeted conserved antigens. These findings suggest that alternative vaccine strategies based on delivery of multiple parasite antigens at low dose may induce effective immunity targeting conserved determinants.In regions where Plasmodium falciparum malaria transmission is high, individuals eventually acquire nonsterile immunity, where low parasitemia may occur in the absence of clinical symptoms. Immunity to blood-stage malaria appears to be predominantly antibody mediated. Transfusion of gamma globulin from immune adults to children with severe malaria is associated with reduced parasitemia and clinical improvement (5). Merozoite surface antigens (2, 6, 32) and variant antigens expressed on the surface of malaria-infected erythrocytes (including PfEMP1) (3, 23) are both targets of protective antibody responses.It is still unclear whether cell-mediated (antibody-independent) immune responses play a major role in naturally acquired immunity to blood-stage malaria in humans (reviewed in reference 9). Loss or suppression of malaria-specific T cells during the course of natural infection may limit the contribution of inflammatory T cells to protective immunity. Reduced numbers of peripheral blood T lymphocytes and diminished proliferative responses to in vitro stimulation with malarial antigens are observed during acute P. falciparum infection (15-17). Animal studies indicate that malaria-specific effector and helper CD4 ϩ T cells are deleted by apoptosis during in...

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Section: Discussionmentioning

confidence: 60%

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

2005

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“…2 compared with that shown in Fig. 1 most likely resulted from the longer interval between primary and secondary immunization in the second experiment (70 versus 47 days), as extending the interval between the two injections has been shown to increase the secondary response to PPS conjugate vaccines (1).…”

Section: Vol 69 2001mentioning

confidence: 86%

Increased Immunogenicity and Induction of Class Switching by Conjugation of Complement C3d to Pneumococcal Serotype 14 Capsular Polysaccharide

Test¹,

Mitsuyoshi²,

Connolly³

et al. 2001

Infect Immun

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Previous studies have demonstrated an adjuvant effect for the C3d fragment of complement C3 when coupled to T-dependent protein antigens. In this study, we examined the antibody response to covalent conjugates of C3d and a T-independent antigen, the capsular polysaccharide of serotype 14 Streptococcus pneumoniae (PPS14). We prepared a conjugate of mouse C3d and PPS14 and compared its immunogenicity with that of a conjugate of PPS14 and ovalbumin (OVA). When BALB/c mice were immunized with PPS14-C3d, there was a significant increase in serum anti-PPS14 concentrations compared with either native PPS14 or control PPS14-glycine conjugates. This was accompanied by a switch in anti-PPS14 from predominantly immunoglobulin M (IgM) to IgG1 by day 25 following primary immunization. Following secondary immunization with PPS14-C3d, there was a marked booster response and a further increase in the ratio of IgG1 to IgM anti-PPS14. Although the primary antibody response to the PPS14-OVA conjugate exceeded that induced by immunization with PPS14-C3d, serum anti-PPS14 concentrations after a second injection of PPS14-C3d were nearly identical to those induced by secondary immunization with PPS14-OVA. Experiments with athymic nude mice suggested that T cells were not required for the adjuvant effect of C3d on the primary immune response to PPS14 but were necessary for enhancement of the memory response after a second injection of PPS14-C3d. These studies show that the adjuvant effects of C3d extend to T-independent antigens as well as T-dependent antigens. As a means of harnessing the adjuvant potential of the innate immune system, C3d conjugates may prove useful as a component of vaccines against encapsulated bacteria.

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“…The finding that all the clones expressed after the conjugate vaccine were restimulated by CP suggests that, functionally, only one type of memory cell exists after multiple immunization with a conjugate vaccine, and it is a memory cell responsive to CP. We do not know whether the precursor cell induced by the conjugate to respond to CP initially belonged to a potentially CPresponsive subset and has the ability to respond to a TD form of the antigen earlier in ontogeny than to the isolated CP, or belonged to a subset that would normally be unresponsive or easily tolerized to the CP (11,16,17), and with exposure to the conjugate vaccine has become CP-responsive. A precedent for the former possibility has been described (16) in the earlier development, in mice, of an antidextran antibody response to immunization with isomaltohexaose coupled to KLH than to immunization with dextran itself.…”

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

“…The antibody response in mice and rabbits to immunization with the H. influenzae b CP is poor, whether administered either as a primary vaccine or as a secondary vaccine after priming with either conjugate vaccines or killed bacteria (2,7,8, and our unpublished observations). In contrast, immunization of rabbits and mice with killed pneumococci or TD forms of pneumococcal CP can prime for secondary responses to the isolated CP (18)(19)(20)(21). However, the secondary response to the isolated CP is not produced until fairly long after primary immunization (19), and is produced later than observed for secondary responses to TD forms of the CP (21).…”

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

Oligosaccharide-protein conjugate vaccines induce and prime for oligoclonal IgG antibody responses to the Haemophilus influenzae b capsular polysaccharide in human infants.

Insel¹,

Anderson²

1986

The Journal of Experimental Medicine

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hnmunity to Haemophilus influenzae type b can be mediated by serum antibody to the capsular polysaccharide (CP) 1 (1). Immunization of human adults and older children with isolated CP induces antibody; however, immunization of young infants fails to induce an antibody response (2, 3). The antibody response is inconsistent, nonboostable, low in titer, and nonprotective in children younger than ~18 mo of age. Children above that age can mount a protective antibody titer, but its magnitude remains less than the adult's until ~4 y of age. The cellular basis of antibody unresponsiveness and the delay of high-magnitude responses is unknown. In an effort to convert the CP to a more thymus-dependent (TD) immunogen, oligosaccharides prepared from the CP (4-6) or the CP itself (7, 8) have been presented with protein carriers. When the oligo conjugate was injected sequentially at ages 2, 4, and 6 mo, a mainly IgM primary and IgG secondary anti-CP antibody response was induced (5). In infants thus primed, titers could be further boosted by immunizing with isolated CP, even at an age normally unresponsive to CP vaccine (5). To elucidate the basis, at the B cell clonal level, of the increased antibody titer induced by the conjugate, and of the accelerated age-acquisition of responsiveness to the isolated CP, we have analyzed IEF patterns of serum antibody of the IgG isotype. Materials and MethodsVaccines. The conjugate vaccine was composed of oligosaccharides 3-10 repeating units in length (derived by hydrolysis of the H. influenzae b CP), coupled by reductive amination to diphtheria toxoid or the antigenically related nontoxic protein, CRM 197 (4). The conjugates contained -4% saccharide and 96% protein, wt/wt (4, 5). The dosage was 25/lg protein injected s.c. Purified CP (2) was later given to some subjects (a 10-ug s.c. injection). The age of the vaccinees and the intervals between vaccination are noted below.Antibody Quantitation. Serum antibody to the H. influenzae b CP was measured in a Farr-type radioantigen binding assay using [ H]CP, and calibrated with standard antiserum SK (Office of Biologics, U.S. Food and Drug Administration) as described (9).

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Secondary IgG responses to type 3 pneumococcal polysaccharide III. T cell requirement for development of B memory

Cited by 32 publications

References 29 publications

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

Heterologous Immunity in the Absence of Variant-Specific Antibodies after Exposure to Subpatent Infection with Blood-Stage Malaria

Increased Immunogenicity and Induction of Class Switching by Conjugation of Complement C3d to Pneumococcal Serotype 14 Capsular Polysaccharide

Oligosaccharide-protein conjugate vaccines induce and prime for oligoclonal IgG antibody responses to the Haemophilus influenzae b capsular polysaccharide in human infants.

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