Considerations for Formulating the Second-Generation Pneumococcal Capsular Polysaccharide Vaccine with Emphasis on the Cross-Reactive Types Within Groups

Jb, Robbins; Austrian, Robert; Cj, Lee; Sc, Rastogi; Schiffman, Gerald; Henrichsen, J.; Ph, Mäkelä; Cv, Broome; Rr, Facklam; Rh, Tiesjema

doi:10.1093/infdis/148.6.1136

Cited by 518 publications

(268 citation statements)

References 111 publications

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“…Although there are many pneumococcal serotypes, only a few serotypes are primarily associated with invasive disease, and current pneumococcal vaccines target those serotypes (12). For instance, serogroup 6 includes commonly pathogenic serotypes and is targeted in all pneumococcal vaccines (13).…”

mentioning

confidence: 99%

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Oliver

Linden

Küntzel

et al. 2013

Journal of Biological Chemistry

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Background: Two atypical serogroup 6 strains have been discovered. Results: They express capsular polysaccharide with two different repeating units and share A150T mutation in WciN␣. Conclusion: This mutation shifts WciN␣ from a galactosyltransferase to a bi-specific glycosyltransferase, creating two new hybrid serotypes: 6F and 6G. Significance: Pneumococci can change capsule serotypes by point mutations and may alter their interactions with the immunity of the host.

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mentioning

confidence: 99%

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Oliver

Linden

Küntzel

et al. 2013

Journal of Biological Chemistry

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“…Over 90 immunochemically distinct types are known. A 14-type mixture of the most prevalent types was selected for vaccination in 1977 and increased to 23 types in 1983 (15). This vaccine is licensed and recommended for adults >65 y and younger subjects with conditions, such as asplenia, that predispose to pneumococcal infection.…”

Section: History Of Vaccinationmentioning

confidence: 99%

Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity

Malley

Anderson

2012

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

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For prevention of Streptococcus pneumoniae (pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens. Given to mice intranasally, this vaccine elicits antibody-independent, CD4+ T lymphocyte-dependent accelerated clearance of pneumococci of various serotypes from the nasopharynx mediated by the cytokine IL-17A. Such immunity may reproduce the natural resistance that develops in infants before capsular antibodies arise. Given by injection, the killed cell vaccine induces bifunctional immunity: plasma antibodies protective against fatal pneumonia challenge, as well as IL-17A–mediated nasopharyngeal clearance. Human testing of this inexpensive candidate vaccine by intramuscular injection is planned. Bacterial cellular vaccines are complex—a challenge for reproducibility. However, when several known protective antigens were deleted, the killed pneumococcal vaccine was still protective. This antigenic redundancy may prevent vaccine escape variants by recombinational loss, which is frequent in pneumococcus. Biochemically defined immunogens with bifunctional activity have also been devised. These immunogens are three-component conjugates in which cell wall teichoic acid (a common antigen capable of T cell activation) is coupled to a genetic fusion of two common pneumococcal proteins: a protective surface antigen and a derivative of pneumolysin, which provides TLR4 agonist activity and induces antitoxic immunity. Such constructs induce accelerated clearance when given intranasally and induce both immune mechanisms when injected. The defined composition permits analysis of structure-function activity.

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“…In some cases there is immunological cross reactivity between related structures which can provide partial protection. The optimal choice of polysaccharide to include in the vaccine is therefore a complex epidemiological problem (Robbins et al 1983). Pneumococcal Types 1 and 5, for example, are important pathogens in South America, but much less important in North America or Europe.…”

Section: Introductionmentioning

confidence: 99%

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Jones

2005

An. Acad. Bras. Ciênc.

170

117

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Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development.This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

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Considerations for Formulating the Second-Generation Pneumococcal Capsular Polysaccharide Vaccine with Emphasis on the Cross-Reactive Types Within Groups

Cited by 518 publications

References 111 publications

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Discovery of Streptococcus pneumoniae Serotype 6 Variants with Glycosyltransferases Synthesizing Two Differing Repeating Units

Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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