Randomized controlled study of the safety and immunogenicity of pneumococcal vaccine formulations containing PhtD and detoxified pneumolysin with alum or adjuvant system AS02Vin elderly adults

Clinical and Vaccine Immunology

Volumn 21, Issue 5, 2014, Pages 651-660

  Pauksens, Karlis ^a   Nilsson, Anna C ^b   Caubet, Magalie ^c   Pascal, Thierry G ^c   Van Belle, Pascale ^c   Poolman, Jan T ^c,e   Vandepapelière, Pierre G ^c,f   Verlant, Vincent ^c   Vink, Peter E ^d  

^a UPPSALA UNIVERSITY HOSPITAL   (Sweden)

^b LUND UNIVERSITY   (Sweden)

^c GSK   (Belgium)

^d GLAXOSMITHKLINE   (United States)

^e CRUCELL HOLLAND BV   (Netherlands)

^f Neovacs SA   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALUMINUM POTASSIUM SULFATE; FRAGILE HISTIDINE TRIAD PROTEIN; IMMUNOLOGICAL ADJUVANT; PLACEBO; PNEUMOCOCCUS POLYSACCHARIDE; PNEUMOCOCCUS VACCINE; PNEUMOLYSIN; ALUMINUM SULFATE; BACTERIAL ANTIGEN; BACTERIAL PROTEIN; BACTERIUM ANTIBODY; OPSONIN; PLY PROTEIN, STREPTOCOCCUS PNEUMONIAE; SAPONIN; STREPTOLYSIN; SUBUNIT VACCINE;

ADJUVANT THERAPY; AGED; AGING; ANTIBODY RESPONSE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DRUG FORMULATION; DRUG SAFETY; FATIGUE; FEMALE; HEADACHE; HUMAN; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOREACTIVITY; INCIDENCE; INJECTION SITE PAIN; INJECTION SITE SWELLING; MALE; MYALGIA; NORMAL HUMAN; PHAGOCYTOSIS; PHASE 1 CLINICAL TRIAL; PNEUMOCOCCAL INFECTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SEROTYPE; SKIN REDNESS; VERY ELDERLY; BLOOD; CLINICAL TRIAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; IMMUNOLOGY; PATHOLOGY; SINGLE BLIND PROCEDURE;

ADJUVANTS, IMMUNOLOGIC; AGED; AGED, 80 AND OVER; ALUM COMPOUNDS; ANTIBODIES, BACTERIAL; ANTIGENS, BACTERIAL; BACTERIAL PROTEINS; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; HUMANS; MALE; OPSONIN PROTEINS; PHAGOCYTOSIS; PLACEBOS; PNEUMOCOCCAL VACCINES; SAPONINS; SINGLE-BLIND METHOD; STREPTOLYSINS; VACCINES, SUBUNIT;

EID: 84899738597     PISSN: 15566811     EISSN: 1556679X     Source Type: Journal    
DOI: 10.1128/CVI.00807-13     Document Type: Article

References (39)

1. Muhammad RD, Oza-Frank R, Zell E, Link-Gelles R, Narayan KM, Schaffner W, Thomas A, Lexau C, Bennett NM, Farley MM, Harrison LH, Reingold A, Hadler J, Beall B, Klugman KP, Moore MR. 2013. Epidemiology of invasive pneumococcal disease among high-risk adults since the introduction of pneumococcal conjugate vaccine for children. Clin. Infect. Dis. 56:e59-e67. http://dx.doi.org/10.1093/ cid/cis971.
2. Westerink MA, Schroeder HW, Jr, Nahm MH. 2012. Immune responses to pneumococcal vaccines in children and adults: rationale for age-specific vaccination. Aging Dis. 3:51-67.
3. Welte T, Torres A, Nathwani D. 2012. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 67:71-79. http://dx.doi.org/10.1136/thx.2009.129502.
4. Wroe PC, Finkelstein JA, Ray GT, Linder JA, Johnson KM, Rifas-Shiman S, Moore MR, Huang SS. 2012. Aging population and future burden of pneumococcal pneumonia in the United States. J. Infect. Dis. 205:1589-1592. http://dx.doi.org/10.1093/infdis/jis240.
5. Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, Hanson CA, Mahoney LD, Shay DK, Thompson WW, Vaccine Safety Datalink. 2003. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N. Engl. J. Med. 348:1747-1755. http://dx.doi.org/10.1056/NEJMoa022678.
6. Moberley SA, Holden J, Tatham DP, Andrews RM. 2008. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst. Rev. (1):CD000422. http://dx.doi.org/10.1002/14651858.CD000422.pub2.
7. Huss A, Scott P, Stuck AE, Trotter C, Egger M. 2009. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ 180:48-58. http://dx.doi.org/10.1503/cmaj.080734.
8. Musher DM. 2012. Editorial commentary: should 13-valent protein-conjugate pneumococcal vaccine be used routinely in adults? Clin. Infect. Dis. 55:265-267. http://dx.doi.org/10.1093/cid/cis364.
9. Ridda I, Musher DM. 2012. Is there a potential role for protein-conjugate pneumococcal vaccine in older adults? Australas. Med. J. 5:231-235. http://dx.doi.org/10.4066/AMJ.2012.1160.
10. World Health Organization. 2008. 23-valent pneumococcal polysaccharide vaccine. WHO position paper. Wkly. Epidemiol. Rec. 83:373-384.
11. Clutterbuck EA, Lazarus R, Yu LM, Bowman J, Bateman EA, Diggle L, Angus B, Peto TE, Beverley PC, Mant D, Pollard AJ. 2012. Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells. J. Infect. Dis. 205:1408-1416. http://dx.doi.org/10.1093/infdis/jis212.
12. Hak E, Grobbee DE, Sanders EA, Verheij TJ, Bolkenbaas M, Huijts SM, Gruber WC, Tansey S, McDonough A, Thoma B, Patterson S, van Alphen AJ, Bonten MJ. 2008. Rationale and design of CAPiTA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults. Neth. J. Med. 66:378-383.
13. Vila-Corcoles A, Ochoa-Gondar O. 2013. Preventing pneumococcal disease in the elderly: recent advances in vaccines and implications for clinical practice. Drugs Aging. http://dx.doi.org/10.1007/s40266-013-0060-5.
14. Centers for Disease Control and Prevention. 2012. Licensure of 13-valent pneumococcal conjugate vaccine for adults aged 50 years and older. MMWR Morb. Mortal. Wkly. Rep. 61:394-395.
15. Scott JA, Hall AJ, Dagan R, Dixon JM, Eykyn SJ, Fenoll A, Hortal M, Jetté LP, Jorgensen JH, Lamothe F, Latorre C, Macfarlane JT, Shlaes DM, Smart LE, Taunay A. 1996. Serogroup-specific epidemiology of Streptococcus pneumoniae: associations with age, sex, and geography in 7,000 episodes of invasive disease. Clin. Infect. Dis. 22:973-981. http://dx.doi.org/10.1093/ clinids/22.6.973. (Pubitemid 26260598)
16. Lipsitch M, Whitney CG, Zell E, Kaijalainen T, Dagan R, Malley R. 2005. Are anticapsular antibodies the primary mechanism of protection against invasive pneumococcal disease? PLoS Med. 2:e15. http://dx.doi.org/10.1371/journal.pmed. 0020015.
17. Malley R. 2010. Antibody and cell-mediated immunity to Streptococcus pneumoniae: implications for vaccine development. J. Mol. Med. (Berl.) 88:135-142. http://dx.doi.org/10.1007/s00109-009-0579-4.
18. Moffitt KL, Malley R. 2011. Next generation pneumococcal vaccines. Curr. Opin. Immunol. 23:407-413. http://dx.doi.org/10.1016/j.coi.2011.04.002.
19. Malley R, Anderson PW. 2012. Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity. Proc. Natl. Acad. Sci. U. S. A. 109:3623-3627. http://dx.doi.org/10.1073/pnas. 1121383109.
20. Plumptre CD, Ogunniyi AD, Paton JC. 2012. Polyhistidine triad proteins of pathogenic streptococci. Trends Microbiol. 20:485-493. http://dx.doi.org/10. 1016/j.tim.2012.06.004.
21. Godfroid F, Hermand P, Verlant V, Denoël P, Poolman JT. 2011. Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infect. Immun. 79:238-245. http://dx.doi.org/10. 1128/IAI.00378-10.
22. Marriott HM, Mitchell TJ, Dockrell DH. 2008. Pneumolysin: a double-edged sword during the host-pathogen interaction. Curr. Mol. Med. 8:497-509. http://dx.doi.org/10.2174/156652408785747924.
23. Lucas R, Czikora I, Sridhar S, Zemskov E, Gorshkov B, Siddaramappa U, Oseghale A, Lawson J, Verin A, Rick FG, Block NL, Pillich H, Romero M, Leustik M, Schally AV, Chakraborty T. 2013. Mini-review: novel therapeutic strategies to blunt actions of pneumolysin in the lungs. Toxins. (Basel) 5:1244-1260. http://dx.doi.org/10.3390/toxins5071244.
24. Garçon N, Leroux-Roels G, Cheng WF. 2011. Vaccine adjuvants, p 89-113. In Garçon N, Cunningham AL, Stanberry LR (ed), Understanding modern vaccines: perspectives in vaccinology. Elsevier BV, Amsterdam, The Netherlands.
25. Vandepapelière P, Horsmans Y, Moris P, Van Mechelen M, Janssens M, Koutsoukos M, Van Belle P, Clement F, Hanon E, Wettendorff M, Garçon N, Leroux-Roels G. 2008. Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers. Vaccine 26:1375-1386. http://dx.doi.org/10.1016/j.vaccine.2007.12.038.
26. Denoël P, Philipp MT, Doyle L, Martin D, Carletti G, Poolman JT. 2011. A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae. Vaccine 29:5495-5501. http://dx.doi.org/10.1016/j.vaccine.2011.05.051.
27. v enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: randomised, controlled trials. Vaccine, in press. http://dx.doi.org/10. 1016/j.vaccine.2013.10.052.
28. Berglund J, Vink P, Tavares Da Silva F, Lestrate P, Boutriau D. 2014. Safety, immunogenicity and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae tri-protein vaccine in a phase 1 randomized controlled study in healthy adults. Clin. Vaccine Immunol. 21:56-65. http://dx.doi.org/10.1128/CVI.00430-13.
29. Romero-Steiner S, Libutti D, Pais LB, Dykes J, Anderson P, Whitin JC, Keyserling HL, Carlone GM. 1997. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin. Diagn. Lab. Immunol. 4:415-422. (Pubitemid 27321773)
30. Borys D, Hausdorff W, Fierens F, Godfroid F, Verlant V. 2012. Progress towards development of a protein-based pneumococcal vaccine, p 27. 8th International Symposium on Pneumococci and Pneumococcal Diseases, Iguaçu Falls, Brazil, 11 to 15 March 2012.
31. Adamou JE, Heinrichs JH, Erwin AL, Walsh W, Gayle T, Dormitzer M, Dagan R, Brewah YA, Barren P, Lathigra R, Langermann S, Koenig S, Johnson S. 2001. Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis. Infect. Immun. 69:949-958. http://dx.doi.org/10.1128/IAI.69.2.949-958.2001. (Pubitemid 32109561)
32. Khan MN, Pichichero ME. 2012. Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine 30:2900-2907. http://dx.doi.org/10.1016/j.vaccine.2012.02.023.
33. Kirkham LA, Kerr AR, Douce GR, Paterson GK, Dilts DA, Liu DF, Mitchell TJ. 2006. Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines. Infect. Immun. 74:586-593. http://dx.doi.org/10.1128/IAI.74.1.586-593.2006. (Pubitemid 43023114)
34. Kamtchoua T, Bologa M, Hopfer R, Neveu D, Hu B, Sheng X, Corde N, Pouzet C, Zimmermann G, Gurunathan S. 2013. Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a single-antigen protein vaccine candidate in adults. Vaccine 31:327-333. http://dx.doi.org/10.1016/j.vaccine. 2012.11.005.
35. Salha D, Szeto J, Myers L, Claus C, Sheung A, Tang M, Ljutic B, Hanwell D, Ogilvie K, Ming M, Messham B, van den Dobbelsteen G, Hopfer R, Ochs MM, Gallichan S. 2012. Neutralizing antibodies elicited by a novel detoxified pneumolysin derivative, PlyD1, provide protection against both pneumococcal infection and lung injury. Infect. Immun. 80:2212-2220. http://dx.doi.org/10. 1128/IAI.06348-11.
36. Alexander JE, Lock RA, Peeters CC, Poolman JT, Andrew PW, Mitchell TJ, Hansman D, Paton JC. 1994. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect. Immun. 62:5683-5688. (Pubitemid 24365020)
37. Paton JC, Lock RA, Lee CJ, Li JP, Berry AM, Mitchell TJ, Andrew PW, Hansman D, Boulnois GJ. 1991. Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to Streptococcus pneumoniae type 19F polysaccharide. Infect. Immun. 59:2297-2304.
38. Ogunniyi AD, Woodrow MC, Poolman JT, Paton JC. 2001. Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA. Infect. Immun. 69:5997-6003. http://dx.doi.org/10.1128/IAI.69.10.5997-6003.2001. (Pubitemid 32885158)
39. Garçon N, Van Mechelen M. 2011. Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Expert Rev. Vaccines 10:471-486. http://dx.doi.org/10.1586/erv.11.29.