EuroPneumo Special Issue / pneumonia 2015 Oct 21;7:I–72


Salmonella outer membrane vesicles displaying high densities

of pneumococcal antigen at the surface offer protection against


Kirsten Kuipers 1 , Maria Daleke-Schermerhorn 2, 3 , Wouter Jong 2, 3 , Corinne ten

Hagen-Jongman 2, 3 , Fred van Opzeeland 1 , Elles Simonetti 1 , Christa van der Gaast 1 , Aldert Zomer 4 ,

Joen Luirink 2, 3 , Marien de Jonge 1


Radboud University Medical Center, Nijmegen, The Netherlands; 2 VU University, Amsterdam, The Netherlands; 3 Aberia Bioscience AB, Stockholm,

Sweden, 4 Utrecht University, Utrecht, The Netherlands

Bacterial outer membrane vesicles (OMVs) are attractive vaccine formulations because of their intrinsic immunostimulatory

properties and non-living nature. In principle, heterologous antigens incorporated into OMVs will elicit specific immune

responses, especially if presented at the surface. In this study, we explored the feasibility of the protein expression

Hbp platform for vaccine development and present an approach for a broadly protective pneumococcal vaccine. We

show that intranasally administered Salmonella OMVs displaying high antigen levels at the surface induced strong

protection in a murine model of pneumococcal colonisation, without the need for a mucosal adjuvant. Reduction in

bacterial recovery from the nasal cavity correlated with local production of antigen-specific IL-17A. Furthermore, the

protective efficacy, the production of antigen-specific IL-17A, and local and systemic IgGs, were all improved at a higher

concentration of the displayed antigen. As only the α1α2 part of PspA elicited strong protection, we investigated which

region(s) in α1α2 could mediate cross-protection between pneumococcal strains using a pneumococcal strain collection

of 350 clinical isolates. IgG cross-reactivity between pneumococcal strains appears to be mediated by 2 specific regions

of α1α2, which, remarkably, are variants present in almost all clinical isolates. Currently, experiments are ongoing to

assess cellular cross-reactivity. As PspA is highly variable among serotypes, the percentage coverage of pneumococcal

strains could potentially be increased by combining the cross-reactive regions from different sequences for surface

display on Salmonella OMVs. Here we demonstrate that intranasally administered OMVs decorated with pneumococcal

antigens induce strong protection. This discovery highlights the importance of an efficient antigen expression system for

development of recombinant OMV-based vaccines. In conclusion, our findings demonstrate the suitability of the Hbp

platform for development of a new generation of OMV vaccines, and illustrate the potential of using this approach to

develop a broadly protective mucosal pneumococcal vaccine.


Calibration of an individual-based transmission model to pre- and

post-PCV pneumococcal carriage

Marc Lipsitch 1 , Thomas Fussell 1 , Sarah Cobey 2 , Daniel Weinberger 3


Harvard TH Chan School of Public Health, Boston, MA, USA; 2 University of Chicago, Chicago, IL, USA; 3 Yale School of Public Health, New Haven, CT,


Predicting the effects of pneumococcal vaccination on carriage of and disease from specific pneumococcal serotypes

requires a sufficiently realistic model of the factors underlying serotype-specific incidence and prevalence before and

after vaccination. We adapted a previously-published model of pneumococcal population dynamics, which includes

serotype-specific variability in duration and within-host competitive ability, as well as serotype-specific and non-specific

acquired immunity, to fit the observed prevalence of pneumococcal serotypes, using carriage data from Massachusetts

before PCV7, during the PCV7 era, and during the PCV13 era. By varying a single parameter for each serotype that

governed both its specific duration and its within-host competitive ability, and varying another parameter governing

overall transmission intensity, the model was able to reproduce observed patterns of serotype-specific prevalence

before vaccine introduction. Following introduction of vaccine, based on fitting to vaccine-type prevalence, a direct

effect of at least a 73% reduction in the acquisition rate of carriage of vaccine types was required to reproduce

observed carriage prevalences, post-vaccine introduction. Serotypes that were not in the vaccine but are part of vaccine

serogroups expanded post-PCV7 more in observed data than in model predictions. We hypothesise that partial crossimmunity

within serogroups may have lowered prevaccine prevalence of these vaccine-related types, and that their

disproportionate expansion may be evidence for such partial cross-immunity. We conclude that calibrated, detailed

pneumonia 2015 Volume 7


Similar magazines