Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice

被引:90
作者
Ferreira, D. M. [1 ]
Darrieux, M. [1 ]
Silva, D. A. [1 ]
Leite, L. C. C. [1 ]
Ferreira, J. M. C., Jr. [2 ]
Ho, P. L. [1 ]
Miyaji, E. N. [1 ]
Oliveira, M. L. S. [1 ]
机构
[1] Inst Butantan, Ctr Biotechnol, BR-05503900 Sao Paulo, Brazil
[2] Inst Butantan, Lab Imunoquim, BR-05503900 Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
STREPTOCOCCUS-PNEUMONIAE INFECTION; CD4(+) T-CELLS; INTRANASAL IMMUNIZATION; NASOPHARYNGEAL CARRIAGE; INTERFERON-GAMMA; PSEUDOMONAS-AERUGINOSA; DENDRITIC CELLS; OTITIS-MEDIA; HOST-DEFENSE; TGF-BETA;
D O I
10.1128/CVI.00395-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.
引用
收藏
页码:636 / 645
页数:10
相关论文
共 55 条
[1]   REMOVAL OF ENDOTOXIN FROM PROTEIN SOLUTIONS BY PHASE-SEPARATION USING TRITON X-114 [J].
AIDA, Y ;
PABST, MJ .
JOURNAL OF IMMUNOLOGICAL METHODS, 1990, 132 (02) :191-195
[2]  
[Anonymous], 1998, Wkly Epidemiol Rec, V73, P187
[3]   Intranasal vaccination with pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection [J].
Arulanandam, BP ;
Lynch, JM ;
Briles, DE ;
Hollingshead, S ;
Metzger, DW .
INFECTION AND IMMUNITY, 2001, 69 (11) :6718-6724
[4]   Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization [J].
Audouy, Sandrine A. L. ;
van Roosmalen, Maarten L. ;
Neef, Jolanda ;
Kanninga, Rolf ;
Post, Eduard ;
van Deemter, Marielle ;
Metselaar, Heidi ;
van Selm, Saskia ;
Robillard, George T. ;
Leenhouts, Kees J. ;
Hermans, Peter W. M. .
VACCINE, 2006, 24 (26) :5434-5441
[5]   Th17 cells and mucosal host defense [J].
Auja, Shean J. ;
Dubin, Patricia J. ;
Kolls, Jay K. .
SEMINARS IN IMMUNOLOGY, 2007, 19 (06) :377-382
[6]   Interleukin-17 in pulmonary host defense [J].
Aujla, Shean J. ;
Dubin, Patricia J. ;
Kolls, Jay K. .
EXPERIMENTAL LUNG RESEARCH, 2007, 33 (10) :507-518
[7]   Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae [J].
Balachandran, P ;
Brooks-Walter, A ;
Virolainen-Julkunen, A ;
Hollingshead, SK ;
Briles, DE .
INFECTION AND IMMUNITY, 2002, 70 (05) :2526-2534
[8]   Antibody-independent, CD4+ T-Cell-Dependent protection against pneumococcal colonization elicited by intranasal immunization with purified pneumococcal proteins [J].
Basset, Alan ;
Thompson, Claudette M. ;
Hollingshead, Susan K. ;
Briles, David E. ;
Ades, Edwin W. ;
Lipsitch, Marc ;
Malley, Richard .
INFECTION AND IMMUNITY, 2007, 75 (11) :5460-5464
[9]  
BRACONIER JH, 1982, J LAB CLIN MED, V100, P279
[10]   Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae [J].
Briles, DE ;
Ades, E ;
Paton, JC ;
Sampson, JS ;
Carlone, GM ;
Huebner, RC ;
Virolainen, A ;
Swiatlo, E ;
Hollingshead, SK .
INFECTION AND IMMUNITY, 2000, 68 (02) :796-800