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


Pneumolysin toxoid as a vaccine adjuvant

Cassandra L Krone 1, 2 , Jenny Herbert 1, 2 , Andrea Mitchell 1, 2 , David R Withers 1 , Tim J Mitchell 1, 2


School of Immunity and Infection, University of Birmingham, Birmingham, UK; 2 Institute of Microbiology and Infection, University of Birmingham,

Birmingham, UK

Streptococcus pneumoniae (the pneumococcus) is a major human pathobiont and can cause a range of diseases including

pneumonia and meningitis. Currently, available vaccines against the pneumococcus are based on the polysaccharide

capsule and as such are serogroup specific. Therefore, there is much interest in developing protein-based vaccines. The

pneumococcal pore-forming toxin pneumolysin (PLY) is an important virulence factor, but also a potential protective

immunogen. We previously made a non-toxic version of PLY (Δ6PLY) that does not form pores. Δ6PLY is immunogenic

in mice and also acts as a mucosal adjuvant for proteins fused to the toxoid. In this study we use a mouse model to

demonstrate that mucosal vaccination with protein fusion vaccines can protect against colonisation. The mechanism

of protection is IL-17 dependant, as protection against colonisation was abrogated in IL-17 knock-out mice. We will

also describe the use of in vitro stimulation assays to investigate the possible mechanisms of the adjuvant activity of

Δ6PLY. Furthermore, use of IL17A-Cre R26R-tdRFP fate mapping reporter mice will enable us to determine which IL-17A

producing cells are involved in the mucosal immune response to Δ6PLY.


Clonal expansion of non-susceptible non-vaccine pneumococci in

non-invasive isolates following conjugate vaccine introduction results

in similar rates of antimicrobial non-susceptibility to the

pre-conjugate-vaccine era

Martha McElligott 1, 2 , Imelda Vickers 1, 2 , Mary Meehan 1 , Mary Cafferkey 1, 2 , Robert Cunney 1, 3 ,

Hilary Humphreys 2, 4


Temple Street Children’s University Hospital, Dublin, Ireland; 2 Royal College of Surgeons in Ireland, Dublin, Ireland; 3 Health Protection Surveillance

Centre, Dublin, Ireland, 4 Beaumont Hospital, Dublin, Ireland

The 7- and 13- valent pneumococcal conjugate vaccines (PCV7/13) were introduced to the Irish childhood immunisation

schedules in 2008 and 2010, respectively. We collected 506 paediatric non-invasive pneumococci from 2009 to 2014 at

Temple St Children’s University Hospital and Our Lady’s Children’s Hospital Crumlin and AMNCH Tallaght during 2013 to

2014. Serotyping and susceptibility testing to 6 different antimicrobials was performed on isolates. Multilocus sequence

typing further characterised 169 isolates non-susceptible to at least 1 antimicrobial. Notable changes occurred in nonsusceptible

clones and serotypes in non-invasive isolates after conjugate vaccine introduction compared to before

conjugate vaccine introduction. In 2007, England 14 -9 and Spain 9V -3 accounted for 12% and 32% of non-susceptible clones,

respectively, but in 2009-2014 their prevalence was just 0% and 2.4%. Both England 14 -9 and Spain 9V -3 were associated

with PCV7 serotypes 14 and 9V. Furthermore, there was a significant decline in non-susceptible PCV7 serotype 6B

belonging to Spain 6B -2 and its variants from 2009 to 2014 (p = 0.0024). Fluctuations occurred in clonal complex 320

associated with non-susceptible PCV13 serotype 19A. A significant increase occurred in non-susceptible non-vaccine

type (NVT) pneumococci from 12% (3/25) in 2007 to 73% (51/69) in 2014 (p < 0.0001). Serotypes 15A (n = 21) and 35B (n

= 22) were the most frequent NVT which were non-susceptible from 2009 onwards. The increase of NVT serotypes 15A

and 35B was largely mediated by clonal expansion of Sweden 15A -25 and its variants (n = 15) and sequence type 558 (n =

21), respectively. Overall, non-susceptibility rates among non-invasive isolates did not change notably during the study

at 23% (2007), 30% (2009), 31% (2010), 21% (2011), 34% (2012), and 41% (2013-2014). This suggests that the increase

in clones expressing NVT has resulted in a similar rate of non-susceptibility among non-invasive pneumococci. Continued

surveillance will determine if non-susceptible NVT pneumococci increase in circulation with sustained conjugate vaccine


pneumonia 2015 Volume 7


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