Prospettive attuali e future della prevenzione della patologia pneumococcica Nicola Principi

PCV-7 e PCV13 ha come carrier CRM197, PCV-10 contiene (8/10 sierotipi) come carrier la proteina D derivata dall’H. influenzae non tipizzabile Le modalità di coniugazione sono differenti

Note to presenter: use of this slide for presentation to an external audience will require copyright permission for these figures Not all serotypes are produced on the same way This might impact of protection given Both manufacturers start with the same 19F polysaccharide, but difference in coupling chemistry and carrier proteins create antigenically distinct conjugates Native 19A structure Native 19F structure PCV10: Cyanylation PCV7 e PCV13: Oxidation + reductive amination Conjugation of 19F PS by reductive amination (Pfizer) results in creation of an additional epitope not present in the native form of 19F PS or in 19F PS conjugated by cyanylation (GSK) The additional epitope appear to induce antibodies with lower (or no) functionality against serotype 19F, as revealed by OPA titre Higher levels of functional antibodies against 19F and 19A PSs were induced by Synflorix™ compared with PCV7, in which 19F PS is conjugated via reductive amination Conserved polysaccharide structure Creation of different configurations and additional epitopes Kim, et al. Anal Biochem 2005; 347: 262–74; Poolman, et al. Clin Vaccine Immunol 2011; 18: 327−36. Weblinks accessed July 2014

Principali ragioni addotte per il mancato inserimento dei sierotipi 3, 6A, 19A in PCV10. Il polisaccaride capsulare del sierotipo 3 anche quando coniugato dà risposte immunitarie scarse e quasi sempre non protettive I sierotipi 6B e 19F, quando opportunamente coniugati, evocano la produzione di anticorpi cross-reactive anche contro i sierotipi 6A e 19A.

Livelli di IgG contro specifici sierotipi prima e dopo la dose di richiamo in bambini di 11 mesi vaccinati con PCV10 o PCV13 (da van Westen et al. Clin Infect Dis 2015)

PCV10: Immunogenicity for Serotype 19A Immunogenicity Parameter Serotype 19F (Present in Vaccine) Serotype 19A (Potentially cross-reactive) PCV10 Overall Antibody Levels (ELISA) % Achieving >0.20g/mL 95.4 (94.0 – 96.5) 22.6 (17.6 – 27.9) % Achieving >0.35g/mL 89.1 (87.1 – 90.9) 8.2 (5.3 – 12.1) Geometric Mean Concentrations 184 (1.71 - 1.98) 0.08 (0.07 – 0.09) Functional Antibody Levels (OPA) % Achieving >1:8 87.7 (83.1 - 91.4) 19.6 (15.0 – 25.0) Geometric Mean Titers 148 (117.8 – 187.5) 8.6 (7.1 – 10.5) Vesikari T et al. Pediatr Infect Dis J 2009;28:S66-76.

Cellule B di memoria sierotipo specifiche prima e dopo la dose di richiamo in bambini di 11 mesi vaccinati con PCV10 o PCV13 (da van Westen et al. Clin Infect Dis 2015)

Surveillance data for serotype 19A IPD (from Sings HL et al Surveillance data for serotype 19A IPD (from Sings HL et al. From ISPPD 2016)

Surveillance data for serotype 19A IPD (from Sings HL et al Surveillance data for serotype 19A IPD (from Sings HL et al. From ISPPD 2016)

Incidence of IPD due to selected serotypes in England and Wales before and after PCV13 introduction (from Waight P, et al. Lancet Infect DIS 2015)

Andamento della ospedalizzazione per CAP negli U. S. A Andamento della ospedalizzazione per CAP negli U.S.A. prima e dopo l’introduzione di PCV-7 (da Grijalva CG et al. Lancet 2007) 1012 ospedali, più di 38 milioni di ricoveri Confronto tra 2001-2004 e 1997-1999

Andamento della ospedalizzazione per CAP pneumococcica negli U. S. A Andamento della ospedalizzazione per CAP pneumococcica negli U.S.A. prima e dopo l’introduzione di PCV-7 (da Grijalva CG et al. Lancet 2007) 1012 ospedali, più di 38 milioni di ricoveri Confronto tra 2001-2004 e 1997-1999

Estimated adjusted vaccine effectiveness of PCV10 against CAP for different case definition (from Diaz J, et al. PloS ONE 2016)

CAP hospitalization rates by age-group and gender in the pre- and post- PCV10 introduction periods (Brazil) (from Sgambatti S, et al. Vaccine 2016)

Monthly and annual rates (per 1000 children) of hospital visits for alveolar CAP in children < 5 years, July 2002 through (Israel) (from Greenberg D et al. Vaccine 2015) o

PCV use in 2012 in Sweden by County Council (from Berglund et al PCV use in 2012 in Sweden by County Council (from Berglund et al. PloS ONE 2014)

All-Cause Pneumonia and Pneumococcal Conjugate Vaccine Introduction (from Berglund et al. PloS ONE 2014)

Table 3. Crude and Adjusted Incidence Rates and Incidence Rate Ratios (IRR) with Corresponding 95% Confidence Intervals (CI) during the pre-PCV7 and PCV7 period, and for County Councils utilizing by 2012 PCV10 and PCV13, among children <2 years old in Sweden. Berglund A, Ekelund M, Fletcher MA, Nyman L (2014) All-Cause Pneumonia Hospitalizations in Children <2 Years Old in Sweden, 1998 to 2012: Impact of Pneumococcal Conjugate Vaccine Introduction. PLoS ONE 9(11): e112211. doi:10.1371/journal.pone.0112211 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0112211

Annual incidence of AOM per 1000 children < 36 months (Israel) (From Ben-Shimol S, et al. Clin Infect Dis 2016

Limitations of available pneumococcal conjugate vaccines (from Pichichero M, et al. Hum Vaccin Immunother 2016)

Impact of S. pneumoniae in AOM with spontaneous tympanic membrane perforation: serotype distribution 4 Years after PCV13 Introduction (from Marchisio P, et al. Pedistr Infec Dis J 2016)

Main pneumococcal antigens for vaccine preparation (from Daniels CC, et al. J Pediatr Pharmacol Ther 2016)

Pneumococcal protein vaccine candidate evaluated in clinical trials (from Pichichero M et al. Hum Vaccin Immunother 2016)