New Vaccines for Prevention of Pneumococcal Infections

Eskola, Juhani; Käyhty, Helena

doi:10.3109/07853899509031936

Cited by 8 publications

(3 citation statements)

References 52 publications

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“…The serotype was reported for 29 isolates of S. pneumoniae from children aged 5 years. Of these, serotypes 6, 14 and 18 were most common, and 90 % were serotypes contained in a candidate heptavalent conjugate vaccine [9].…”

Section: Resultsmentioning

confidence: 99%

Invasive pneumococcal infection in South and West England

Smith

Stuart

Andrews³

et al. 1998

Epidemiol. Infect.

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Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines.

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Section: Resultsmentioning

confidence: 99%

Invasive pneumococcal infection in South and West England

Smith

Stuart

Andrews³

et al. 1998

Epidemiol. Infect.

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“…B cell activation results in immunoglobulin M (IgM) production but limited class switching, no affinity maturation, and little, if any, development of memory cells (24). By conjugation of PS to various proteins, their immunogenicity may be increased, probably by recruitment of T-cell help through linked recognition (11,19,27,32).…”

mentioning

confidence: 99%

Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines with Nontoxic Mutants ofEscherichia coliHeat-Labile Enterotoxins as Adjuvants Protects Mice against Invasive Pneumococcal Infections

Jakobsen

Schulz

Pizza³

et al. 1999

Infect Immun

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Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) ofEscherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

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“…Vaccination with PPS stimulates antibody production (5,7,37) and is protective in healthy adults (3,33), but immunogenicity is low in certain groups at risk (22) and in children under 2 years of age (10,14,23). To increase immunogenicity, protein-conjugated PPS vaccines are being developed (1,11,32).…”

mentioning

confidence: 99%

Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine

Vidarsson¹,

Sigurdardottir²,

Guðnason³

et al. 1998

Infect Immun

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Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741,r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.

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New Vaccines for Prevention of Pneumococcal Infections

Cited by 8 publications

References 52 publications

Invasive pneumococcal infection in South and West England

Invasive pneumococcal infection in South and West England

Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines with Nontoxic Mutants ofEscherichia coliHeat-Labile Enterotoxins as Adjuvants Protects Mice against Invasive Pneumococcal Infections

Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine

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