Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce immunologic memory

Åhman, Heidi; Käyhty, Helena; Lehtonen, Hannele; Leroy, Odile; Froeschle, James E.; Eskola, Juhani

doi:10.1097/00006454-199803000-00008

Cited by 121 publications

(74 citation statements)

References 19 publications

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“…Protective immunity against both invasive disease [16,17] and otitis media [18] has been demonstrated after vaccination of infants with pneumococcal conjugate vaccines. In addition, pneumococcal conjugate vaccines induce PS-specific memory B cells [19][20][21], similar to what has been observed after immunization with protein antigens.…”

Section: Introductionsupporting

confidence: 60%

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

et al. 2006

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Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults

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Section: Introductionsupporting

confidence: 60%

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

et al. 2006

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“…Although T cell help is required for the primary induction of an anticapsular Ab response by capsular PS-protein conjugate vaccines, it is the Abs induced by such vaccines that are the effectors of immunity. Moreover, the T cell help is required at the time of immunization with conjugate vaccines, to induce affinity maturation, class switching, and B cell memory (19,20), but may not be required at the time of challenge, as it is in the experiments described here. Stimulation of antigen-specific CD4 ϩ T cells by Group A streptococci has recently been described, but no evidence for a protective role of these cells was obtained (21).…”

Section: Discussionmentioning

confidence: 99%

CD4⁺T cells mediate antibody-independent acquired immunity to pneumococcal colonization

Malley

Trzciński

Srivastava

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

306

283

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Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated wholecell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4 ؉ T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8 ؉ T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4 ؉ T cells at the time of challenge.Streptococcus pneumoniae ͉ cell-mediated immunity ͉ vaccine A lmost 1 million children in the developing world die of infections due to Streptococcus pneumoniae (pneumococcus) each year (1). Pneumococcus is considered an ''extracellular'' bacterial pathogen, i.e., it is killed upon ingestion by phagocytic cells. Ingestion is facilitated by antibody (Ab) to its capsular polysaccharides (PS), of which there are at least 90 different serotypes. The two existing pneumococcal vaccines are based on injected mixtures of PS. Plain (unconjugated) PS vaccine contains 23 serotypes but is not efficacious in children Ͻ2 years old and therefore fails to protect those at highest risk. Protein-conjugated PS contains seven serotypes and protects infants (2), but it is difficult to manufacture (resulting in repeated shortages), is expensive, needs refrigeration, requires multiple injections, and does not include many of the capsular serotypes that cause pneumococcal disease in the developing world. Furthermore, serotype replacement, whereby pneumococcal serotypes not included in the conjugate vaccine become more prevalent causes of colonization and disease, has already been observed in clinical trials (3) and in epidemiologic studies (4) after implementation of conjugate vaccine immunization programs. Therefore, despite the success of the capsule-based vaccines, alternative strategies are urgently needed.The success of serum therapy (passive transfer of anticapsular Ab from hyperimmune animals) and the efficacy of PS and PS-protein conjugate vaccines have clearly demonstrated that anticapsular Ab alone is sufficient to treat or prevent pneumococcal disease. Furthermore, studies in animals (5) and humans (6) clearly demonstrate that antica...

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“…Glycoconjugate vaccines are composed of capsular polysaccharide conjugated to an immunogenic protein carrier, such as tetanus toxoid (TT), 4 or keyhole limpet hemocyanin (KLH) and generate a T cell-dependent Ab response to the polysaccharide Ags (4,6,7). Despite the success of the Haemophilus influenzae type B glycoconjugate vaccine (8), there are still a number of potential problems with the use of glycoconjugates.…”

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confidence: 99%

Antibodies to Keyhole Limpet Hemocyanin Cross-React with an Epitope on the Polysaccharide Capsule of Cryptococcus neoformans and Other Carbohydrates: Implications for Vaccine Development

May

Beenhouwer

Scharff

2003

The Journal of Immunology

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Cryptococcus neoformans causes a life-threatening meningoencephalitis in AIDS patients. Mice immunized with a glycoconjugate vaccine composed of the glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide conjugated to tetanus toxoid produce Abs that can be either protective or nonprotective. Because nonprotective Abs block the efficacy of protective Abs, an effective vaccine must focus the Ab response on a protective epitope. Mice immunized with peptide mimetics of GXM conjugated to keyhole limpet hemocyanin (KLH) with glutaraldehyde developed Abs to GXM. However, control peptides P315 and P24 conjugated to KLH also elicited Abs to GXM. GXM-binding Abs from mice immunized with P315-KLH were inhibited by KLH treated with glutaraldehyde (KLH-g), but not by P315. Furthermore, KLH-g inhibited binding of GXM by serum of mice immunized with GXM-TT, indicating that glutaraldehyde treatment of KLH reveals an epitope(s) that cross-reacts with GXM. Vaccination with KLH-g or unmodified KLH elicited Abs to GXM, but did not confer protection against C. neoformans, suggesting the cross-reactive epitope on KLH was not protective. This was supported by the finding that 4H3, a nonprotective mAb, cross-reacted strongly with KLH-g. Sera from mice immunized with either native KLH or KLH-g cross-reacted with several other carbohydrate Ags, many of which have been conjugated to KLH for vaccine development. This study illustrates how mAbs can be used to determine the efficacy of potential vaccines, in addition to describing the complexity of using KLH and glutaraldehyde in the development of vaccines to carbohydrate Ags.

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Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce immunologic memory

Abstract: The PncD conjugate vaccine is immunogenic and able to induce immunologic memory.

Cited by 121 publications

References 19 publications

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

CD4⁺T cells mediate antibody-independent acquired immunity to pneumococcal colonization

Antibodies to Keyhole Limpet Hemocyanin Cross-React with an Epitope on the Polysaccharide Capsule of Cryptococcus neoformans and Other Carbohydrates: Implications for Vaccine Development

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Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce immunologic memory

Abstract: The PncD conjugate vaccine is immunogenic and able to induce immunologic memory.

Cited by 121 publications

References 19 publications

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

CD4+T cells mediate antibody-independent acquired immunity to pneumococcal colonization

Antibodies to Keyhole Limpet Hemocyanin Cross-React with an Epitope on the Polysaccharide Capsule of Cryptococcus neoformans and Other Carbohydrates: Implications for Vaccine Development

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CD4⁺T cells mediate antibody-independent acquired immunity to pneumococcal colonization