First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants

Koskela, Markku; Leinonen, Maija; Häivä, Veli‐Mies; Timonen, M.; Mäkelä, P. Helena

doi:10.1097/00006454-198601000-00009

Cited by 127 publications

(53 citation statements)

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“…The clinical symptoms and signs of pneumonia may be confusing, infants have weak serological responses [12,13], and even radiological diagnosis is difficult at that age [24]. Moreover, infants have lower responses than older children in nonspecific host response parameters [9,10], as seen in the present study.…”

Section: Discussionsupporting

confidence: 47%

“…The method, with minor modifications, was the same as described previously [11]. The methods have been validated in healthy children, and the diagnostic criteria were as follows: the presence of PNC antigen in acute serum or urine [2,3]; a threefold or greater rise in IgM or IgG antibodies to C-PS or CPS in paired sera [2,12,13]; a twofold or greater rise in IgG antibodies to PNL in paired sera [2,14]; or the presence of immune complexes in either acute or convalescent serum [15]. The antigen assays were positive in 15 cases, antibody assays in 22 cases, and immune complex assays in 28 cases.…”

Section: Methodsmentioning

confidence: 99%

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White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children

Korppi

Heiskanen‐Kosma²,

Leinonen³

1997

Eur Respir J

147

109

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White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. M. Korppi, T. Heiskanen-Kosma, M. Leinonen. ©ERS Journals Ltd 1997. ABSTRACT: We evaluated the applicability of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), and absolute neutrophil count (ANC), in the screening of pneumococcal (PNC) pneumonia in children.In 1981-1982, 161 children were treated for radiologically verified communityacquired pneumonia in the hospital during a period of 12 months. The Streptococcus pneumoniae aetiology of infection was studied by antigen, antibody and immune complex assays in acute and convalescent sera. In acute blood samples, CRP was measured by the immunonephelometric method, ESR by the Westergren method, WBC using an automatic cell counter, and thereafter the ANC was calculated after microscopic examination of peripheral smears.CRP and ESR were significantly higher in patients with alveolar (n=53) than in those with interstitial (n=108) pneumonia. CRP, ESR and ANC were significantly higher in PNC (n=29) than in viral (n=23) pneumonia. The values in mixed PNC and viral infections (n=17) were approximately midway between PNC and viral cases. All cases with serologic evidence of S. pneumoniae aetiology were combined (n=46) for calculation of diagnostic parameters. When a cut-off limit of 60 mg·L -1 was used, CRP had a sensitivity of 26% and a specificity of 83% in the screening of PNC pneumonia.We conclude that C-reactive protein and erythrocyte sedimentation rate have a limited capacity to differentiate between pneumococcal and nonpneumococcal pneumonia. C-reactive protein is recommended as the first-line method of screening, and the value of 60 mg·L -1 as the cut-off limit. Eur Respir J 1997; 10: 1125-1129

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Section: Discussionsupporting

confidence: 47%

Section: Methodsmentioning

confidence: 99%

White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children

Korppi

Heiskanen‐Kosma²,

Leinonen³

1997

Eur Respir J

147

109

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“…This vaccine is licensed and recommended for adults >65 y and younger subjects with conditions, such as asplenia, that predispose to pneumococcal infection. Because of the extreme age dependence of the human antipolysaccharide response, however, CP vaccine is ineffective in infants (16)(17)(18). Another seminal finding of the Rockefeller group, shown with pneumococcus, was that coupling of CPs or even their immunodeterminant sugars to carrier proteins increases the CP-reactive antibody response (19,20).…”

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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“…The present vaccine strategy relies on 23-valent capsular polysaccharide vaccine for adults and 7-valent polysaccharide-protein conjugate vaccine for young children. Unfortunately, the 23-valent vaccine is not as efficacious as would be desired, and the 7-valent vaccine is too restricted in the polysaccharides that it contains to be able to protect against all disease, especially in the developing world (4,13,15,19,20,31). A number of protein vaccine candidates are currently being investigated.…”

mentioning

confidence: 99%

Relative Roles of Genetic Background and Variation in PspA in the Ability of Antibodies to PspA To Protect against Capsular Type 3 and 4 Strains of Streptococcus pneumoniae

et al. 2003

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Pneumococcal surface protein A (PspA) is able to elicit antibodies in mice and humans that can protect mice against fatal infection with Streptococcus pneumoniae. It has been observed that immunization with a single family 1 PspA can protect mice against infections with capsular type 3 or 6B strains expressing PspA family 1 or 2. However, several studies have shown that immunity to PspA is less efficacious against several capsular type 4 strains than against strains of capsular types 3, 6A, and 6B. To determine whether the greater difficulty in protecting against capsular type 4 strains resulted from differences in their PspAs or from differences in their genetic backgrounds, we performed protection experiments using four different challenge strains: a capsular type 3 strain expressing a family 1 PspA (WU2), a capsular type 4 strain expressing a family 2 PspA (TIGR4), and genetically engineered variants of WU2 and TIGR4 expressing each other's PspAs. Prior to infection, the mice were immunized with recombinant family 1 or family 2 PspA. The results revealed that much of the difficulty in protecting against capsular type 4 strains was eliminated when mice were immunized with a homologous PspA of the same PspA family. However, regardless of which PspA the strains expressed, those on the TIGR4 background were about twice as hard to protect against as WU2 strains expressing the same PspA based on the efficacy rates seen in our experiments. These results point out the importance of including more than one PspA in any PspA vaccines developed for human use.

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First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants

Cited by 127 publications

References 0 publications

White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children

White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children

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

Relative Roles of Genetic Background and Variation in PspA in the Ability of Antibodies to PspA To Protect against Capsular Type 3 and 4 Strains of Streptococcus pneumoniae

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