Pneumococcal vaccines: an update on current strategies

Bogaert, Debby; Hermans, Peter W. M.; Adrian, Peter V.; Rümke, H. C.; Groot, Ronald de

doi:10.1016/j.vaccine.2003.11.038

Cited by 170 publications

(123 citation statements)

References 105 publications

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“…The relationship between PPS1-specific Ab levels and protection against pneumococcal infection was highly significant in the experiments reported here, which is in agreement with our previous results [26,29]. This indicates that the PPS1-specific Ab are protecting the mice in this model, which is in agreement with PPS-specific Ab-mediating complement-dependent opsonophagocytosis being the main protective mechanism against pneumococcal infections [30,31].…”

Section: Discussionsupporting

confidence: 93%

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

et al. 2009

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IC31® is a novel adjuvant which combines the immunostimulatory effects of an 11‐mer antibacterial peptide (KLKL5KLK) and a synthetic oligodeoxynucleotide (ODN1a) which is a Toll‐like receptor 9 agonist without containing cytosine phosphate guanine (CpG) motifs. The effects of IC31® on neonatal immune response to vaccination have not been reported. Neonatal mice were immunized once or twice with a Streptococcus pneumoniae serotype 1 polysaccharide conjugate containing Tetanus Toxoid (Pnc1‐TT) carrier protein, with or without IC31® or CpG‐ODN. IC31® significantly enhanced IgG1, IgG2a and IgG2b antibodies (Ab) to the serotype 1 polysaccharide. One dose of Pnc1‐TT and low dose IC31® elicited high Ab levels that protected the neonatal mice completely from bacteraemia and significantly reduced lung infection following i.n. challenge with serotype 1 pneumococcal strain. One‐sixth of an adult murine dose of IC31® was sufficient and optimal for induction of protective immunity in neonatal mice. Two doses of Pnc1‐TT with or without adjuvants protected the neonatal mice completely, but more rapid Ab response was observed when IC31® was given with the Pnc1‐TT. IC31® is a promising new adjuvant for neonatal vaccinations, rapidly enhancing protective humoral responses when combined with Pnc1‐TT.

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Section: Discussionsupporting

confidence: 93%

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

et al. 2009

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“…Streptococcus pneumoniae (Pn) are responsible for the majority of life-threatening cases of septicemia, meningitis, and pneumonia in neonates (1,2). Gram-positive bacteria, such as GBS and Pn, are classified into serotypes according to the unique carbohydrate sequence of the bacterial surface capsular polysaccharide (CPS) and protein antigens.…”

Section: S Treptococcus Agalactiae [Group B Streptococcus (Gbs)] Andmentioning

confidence: 99%

Understanding the bacterial polysaccharide antigenicity ofStreptococcus agalactiaeversusStreptococcus pneumoniae

Kadirvelraj

González-Outeiriño

Foley

et al. 2006

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

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Bacterial surface capsular polysaccharides (CPS) that are similar in carbohydrate sequence may differ markedly in immunogenicity and antigenicity. The structural origin of these phenomena is poorly understood. Such a case is presented by the Gram-positive bacteria Streptococcus agalactiae (Group B Streptococcus; GBS) type III (GBSIII) and Streptococcus pneumoniae (Pn) type 14 (Pn14), which share closely related CPS sequences. Nevertheless, antibodies (Abs) against GBSIII rarely cross-react with the CPS from Pn14. To establish the origin for the variation in CPS antigenicity, models for the immune complexes of CPS fragments from GBSIII and Pn14, with the variable fragment (Fv) of a GBS-specific mAb (mAb 1B1), are presented. The complexes are generated through a combination of comparative Ab modeling and automated ligand docking, followed by explicitly solvated 10-ns molecular dynamics simulations. The relationship between carbohydrate sequence and antigenicity is further quantified through the computation of interaction energies using the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method, augmented by conformational entropy estimates. Despite the electrostatic differences between Pn14 and GBSIII CPS, analysis indicates that entropic penalties are primarily responsible for the loss of affinity of the highly flexible Pn14 CPS for mAb 1B1. The similarity of the solution conformation of the relatively rigid GBSIII CPS with that in the immune complex characterizes the previously undescribed 3D structure of the conformational epitope. The analysis provides a comprehensive interpretation for a large body of biochemical and immunological data related to Ab recognition of bacterial polysaccharides and should be applicable to other Ab-carbohydrate interactions. S treptococcus agalactiae [Group B Streptococcus (GBS)] andStreptococcus pneumoniae (Pn) are responsible for the majority of life-threatening cases of septicemia, meningitis, and pneumonia in neonates (1, 2). Gram-positive bacteria, such as GBS and Pn, are classified into serotypes according to the unique carbohydrate sequence of the bacterial surface capsular polysaccharide (CPS) and protein antigens. Serotypes vary in antigenicity, immunogenicity, virulence, and geographical distribution (3). Quantification of the structural and dynamic properties responsible for the affinity and specificity of antigenic oligosaccharide-antibody (Ab) interactions is a crucial step in furthering the understanding of the immune response to bacterial and fungal pathogens. In GBS, the CPS is a high-molecularweight polymer composed of varying sequences of ␤-D-, and sometimes L-rhamnopyranose. The glyceryl side chain of the Neu5Ac residues may also be Oacetylated (4). In all GBS strains identified to date, the Neu5Ac residues occur in the terminal position on the side-chain branches of the polymeric repeat unit of the CPS. They play an important role in defining the antigenicity and immunogenicity of the CPS (5). Variations within the CPS sequence result in the nine kno...

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“…S. pneumoniae is the leading cause of bacterial pneumonia worldwide amongst the immuno compromised, the elderly, children under the age of 5, and adults in the developed world which is likely to increase with an aging population (Wardlaw et al, 2006). Currently, two pneumococcal vaccine types are available, polysaccharide vaccine (23-valent) and conjugate vaccine (10 or 13-valent) (Bogaert et al, 2004;Wang and Curtiss III, 2014). The conjugate vaccines have shown higher efficacy for invasive infections compared to polysaccharide vaccines; but have lower levels of protection against mucosal diseases, such as pneumonia.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Kunda

Alfagih

Miyaji

et al. 2015

International Journal of Pharmaceutics

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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immune compromised, the very young and the old, and remains one of the leading causes of death.A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ~150 nm and achieved ~ 20 µg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.

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Pneumococcal vaccines: an update on current strategies

Cited by 170 publications

References 105 publications

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

Understanding the bacterial polysaccharide antigenicity ofStreptococcus agalactiaeversusStreptococcus pneumoniae

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

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Pneumococcal vaccines: an update on current strategies

Cited by 170 publications

References 105 publications

IC31®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

IC31®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

Understanding the bacterial polysaccharide antigenicity ofStreptococcus agalactiaeversusStreptococcus pneumoniae

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Contact Info

Product

Resources

About

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice

IC31^®, a Two‐Component Novel Adjuvant Mixed with a Conjugate Vaccine Enhances Protective Immunity against Pneumococcal Disease in Neonatal Mice