A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children

Mc, Steinhoff; Edwards, Kathryn M.; Keyserling, Harry L.; Ml, Thoms; Johnson, Cynthia; Madore, Dace V.; Hogerman, Deborah A.

doi:10.1097/00006454-199405000-00007

Cited by 96 publications

(43 citation statements)

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“…This process is thought to work throughout the recruitment of T-cell help, which transforms the antipolysaccharide immune response from a T-cell-independent to a T-cell-dependent response (24). However, it seems that the immunogenicity of pneumococcal conjugates is lower than that of Hib vaccines (26). In particular, immune responses to serotype 6B have repeatedly been shown to be poor.…”

Section: Discussionmentioning

confidence: 99%

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Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

et al. 2000

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There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 g/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 g/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

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Section: Discussionmentioning

confidence: 99%

“…Their efficacy is currently being tested in field trials, and they have been shown to induce antipolysaccharide antibodies in young infants (1,14,26).…”

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confidence: 99%

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

et al. 2000

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“…Studies conducted during the second year of life showed that the heptavalent PncOMPC conjugate was more immunogenic than the PS vaccine (44,45). Different formulations of PncCRM have also been tested in toddlers (46). Conjugates were more immunogenic than the PS vaccine; furthermore, the PS conjugate was more immunogenic than the OS conjugate.…”

Section: Adults and Toddlersmentioning

confidence: 99%

New Vaccines for Prevention of Pneumococcal Infections

Eskola

Käyhty

1995

Annals of Medicine

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“…Vi-rEPA has also been reported to be safe when delivered at 2, 4, and 6 months of age. Additionally, a recent Cochrane review (6) reported a protective efficacy of 55% (95% confidence interval [CI], 30 to 70%) at 3 years with one dose of Vi-polysaccharide vaccine and 87% (95% CI, 56 to 96%) at 2.3 years with two doses of Vi-rEPA.The immunogenicity of the polysaccharide component of a conjugate is affected by different factors, like size and structure of the polysaccharide component, the carrier protein, the conjugation chemistry, the ratio of saccharide to protein, and the eventual presence of free saccharide in the vaccine conjugate (4,23,24,27,34,(36)(37)(38). These factors need to be carefully optimized to produce an effective vaccine.…”

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confidence: 99%

“…The immunogenicity of the polysaccharide component of a conjugate is affected by different factors, like size and structure of the polysaccharide component, the carrier protein, the conjugation chemistry, the ratio of saccharide to protein, and the eventual presence of free saccharide in the vaccine conjugate (4,23,24,27,34,(36)(37)(38). These factors need to be carefully optimized to produce an effective vaccine.…”

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confidence: 99%

Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM ₁₉₇ Conjugate as a Vaccine for Salmonella enterica Serovar Typhi

Rondini

Micoli

Lanzilao

et al. 2011

Clin Vaccine Immunol

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Typhoid fever remains a major health problem in developing countries. Young children are at high risk, and a vaccine effective for this age group is urgently needed. Purified capsular polysaccharide from Salmonella enterica serovar Typhi (Vi) is licensed as a vaccine, providing 50 to 70% protection in individuals older than 5 years. However, this vaccine is ineffective in infants. Vi conjugated to a carrier protein (i.e., an exoprotein A mutant from Pseudomonas aeruginosa [rEPA]) is highly immunogenic, provides long-term protection, and shows more than 90% protective efficacy in children 2 to 5 years old. Here, we describe an alternative glycoconjugate vaccine for S. Typhi, Vi-CRM 197 , where Vi was obtained from Citrobacter freundii WR7011 and CRM 197 , the mutant diphtheria toxin protein, was used as the carrier. We investigated the optimization of growth conditions for Vi production from C. freundii WR7011 and the immunogenicity of Vi-CRM 197 conjugates in mice. The optimal saccharide/protein ratio of the glycoconjugates was identified for the best antibody production. We also demonstrated the ability of this new vaccine to protect mice against challenge with Vi-positive Salmonella enterica serovar Typhimurium.Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic disease which remains a major public health problem, predominantly in children in developing countries. Estimates of the global burden of typhoid fever range from 17 to 22 million cases per year with 216,000 to 600,000 associated annual deaths (2, 9). S. Typhi expresses a virulence (Vi) capsule encoded in the viaB locus of Salmonella pathogenicity island 7 (SPI7), which allows S. Typhi to modulate host responses during infection by evading innate immune surveillance (25,26). Vi is also the main target for vaccines and a major protective antigen against typhoid fever. One of the two currently licensed typhoid fever vaccines is unconjugated Vi polysaccharide, available in more than 90 countries (41).Vi consists of repeating (␣1-4)-2-deoxy-2-N-acetyl galacturonic acid moieties and, similar to other polysaccharides consisting of repeating epitopes, is classified as thymus-independent type 2 (Ti-2) antigen (33). These types of polysaccharides provoke an immune response which is age related, with children under 2 years of age generally poor responders. Additionally, Ti-2 antigens lack affinity maturation of antibody response, generate limited immunologic memory and no booster effect, and produce predominantly immunoglobulin isotype IgM with limited class switching (1). The switch from IgM-to IgG-secreting B cells requires interaction with an activated antigen-specific CD4 ϩ T helper lymphocyte, which can be engaged by the conjugation of the polysaccharide to a carrier protein. Vi, as a Ti-2 antigen, does not generate immunological memory, and antibodies induced by Vi are not able to be boosted by repeated vaccinations (16,40).In contrast, Vi conjugated to a carrier protein provides a valid solution against those m...

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A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children

Cited by 96 publications

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Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

New Vaccines for Prevention of Pneumococcal Infections

Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM ₁₉₇ Conjugate as a Vaccine for Salmonella enterica Serovar Typhi

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A randomized comparison of three bivalent Streptococcus pneumoniae glycoprotein conjugate vaccines in young children

Cited by 96 publications

References 0 publications

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

New Vaccines for Prevention of Pneumococcal Infections

Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM 197 Conjugate as a Vaccine for Salmonella enterica Serovar Typhi

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Product

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Evaluation of the Immunogenicity and Biological Activity of the Citrobacter freundii Vi-CRM ₁₉₇ Conjugate as a Vaccine for Salmonella enterica Serovar Typhi