Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in adults: A Phase 1 randomised clinical trial

Entwisle, Claire; Hill, Sue; Pang, Yin; Joachim, Michael V.; McIlgorm, Ann; Colaco, Camilo; Green, David; D'Argoeuves, Polly De Gorguette; Bailey, Chris

doi:10.1016/j.vaccine.2017.10.076

Cited by 33 publications

(28 citation statements)

References 23 publications

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“…These results show the strong ability of RrgA to elicit an antibody response, which can be important when building the natural immunity toward pneumococcal carriage in children (Ahmed et al, ). Notably, from a recent clinical trial of a novel vaccine candidate, PnuBioVax, performed in healthy young adults, it was observed that most subjects receiving the vaccine had ≥ 2‐fold increase in antibodies against a group of pneumococcal proteins, including RrgA (Entwisle et al, ). Gianfaldoni et al investigated the immunogenicity of RrgA in vivo mice.…”

Section: Introductory Paragraphmentioning

confidence: 99%

The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease

Iovino

Nannapaneni

Henriques‐Normark

et al. 2020

Molecular Microbiology

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The Gram‐positive bacterium Streptococcus pneumoniae, the pneumococcus, is an important commensal resident of the human nasopharynx. Carriage is usually asymptomatic, however, S. pneumoniae can become invasive and spread from the upper respiratory tract to the lungs causing pneumonia, and to other organs to cause severe diseases such as bacteremia and meningitis. Several pneumococcal proteins important for its disease‐causing capability have been described and many are expressed on the bacterial surface. The surface located pneumococcal type‐1 pilus has been associated with virulence and the inflammatory response, and it is present in 20%–30% of clinical isolates. Its tip protein RrgA has been shown to be a major adhesin to human cells and to promote invasion through the blood‐brain barrier. In this review we discuss recent findings of the impact of RrgA on bacterial colonization of the upper respiratory tract and on pneumococcal virulence, and use epidemiological data and genome‐mining to suggest trade‐off mechanisms potentially explaining the rather low prevalence of pilus‐1 expressing pneumococci in humans.

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Section: Introductory Paragraphmentioning

confidence: 99%

The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease

Iovino

Nannapaneni

Henriques‐Normark

et al. 2020

Molecular Microbiology

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“…The MAV approach therefore offers a promising opportunity for a novel next-generation S. pneumoniae vaccine and has recently completed a phase I trial in 36 subjects (ClinicalTrials.gov registry number NCT0257635 [52]).…”

Section: Discussionmentioning

confidence: 99%

A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

Chan¹,

Entwisle

Ercoli³

et al. 2019

Infect Immun

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Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae.

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“…In the preclinical study, rabbit sera immunized with PnuBioVax showed the killing of the vaccine strainTIGR4, and also serotype strains 6B, 19F, and 15B in an opsonophagocytic killing assay. Moreover, incubation of a number of pneumococcal strains in the immunized sera led to agglutination of the bacteria, inhibition of pneumolysin-mediated lysis of erythrocytes and reduced bacterial invasion of lung epithelial cells in vitro [127,128]. Hence, PnuBioVax offers the potential for broad-based protection via multiple mechanisms of action irrespective of serotypes.…”

Section: Promising Pneumococcal Vaccines In Clinical Trialsmentioning

confidence: 99%

“…Hence, PnuBioVax offers the potential for broad-based protection via multiple mechanisms of action irrespective of serotypes. PnuBioVax had undergone a Phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT02572635) sponsored by ImmunoBiology Limited (UK) and it was found to be safe and immunogenic in healthy adults (18-40 years) [128].…”

Section: Promising Pneumococcal Vaccines In Clinical Trialsmentioning

confidence: 99%

Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection

et al. 2020

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Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.

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Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in adults: A Phase 1 randomised clinical trial

Cited by 33 publications

References 23 publications

The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease

The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease

A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection

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