Nasal vaccination with CpG oligodeoxynucleotide induces protective immunity against nontypeable Haemophilus influenzae in the nasopharynx

被引:23
作者
Abe, N [1 ]
Kodama, S [1 ]
Hirano, T [1 ]
Eto, M [1 ]
Suzuki, M [1 ]
机构
[1] Oita Univ, Fac Med, Dept Otolaryngol, Oita 8795593, Japan
关键词
CpG; P6; NTHi; nasal vaccine; mucosal immunity;
D O I
10.1097/01.mlg.0000199740.04730.d4
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objectives: Nasal vaccination is an effective therapeutic regimen for preventing otitis media. Since cholera toxin (CT) is toxic, an alternative adjuvant is required for the development of a nasal vaccine. The efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. Methods: Mice were immunized intranasally with P6 protein of nontypeable Haemophilus influenzae (NTHi) and adjuvant, CT, or CpG ODN, and P6-specific antibody responses were examined. The expression of P6-specifie cytokine mRNA in splenic CD4(+) T cells was also determined. In addition, NTHi challenges were performed and the NTHi was quantified in nasal washes. Results: P6-specific IgA in nasal wash and serum IgG titers were elevated significantly after nasal immunization. The IgG1/IgG2a ratio in serum from P6+CpG-immunized mice was less than that of P6+CT-immunized mice. Although IL-6 was expression similarly in both groups, IFN-gamma expression was greater in P6+CpG-immunized mice than in P6+CT-immunized mice. Enhanced clearance of NTHi from the nasopharynx was also shown equally in both groups. Conclusion: These results indicate that CpG ODN might be an effective mucosal adjuvant, acting by mechanisms that are different from CT. These findings suggest that nasal vaccination with P6 and CpG ODN might be an effective regimen for the induction of NTHi-specifie protective immunity.
引用
收藏
页码:407 / 412
页数:6
相关论文
共 16 条
[1]   Intranasal vaccination with recombinant P6 protein and adamantylamide dipeptide as mucosal adjuvant confers efficient protection against otitis media and lung infection by nontypeable Haemophilus influenzae [J].
Bertot, GM ;
Becker, PD ;
Guzmán, CA ;
Grinstein, S .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (07) :1304-1312
[2]  
FINKELMAN FD, 1990, ANNU REV IMMUNOL, V8, P303, DOI 10.1146/annurev.iy.08.040190.001511
[3]   Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract [J].
Gallichan, WS ;
Woolstencroft, RN ;
Guarasci, T ;
McCluskie, MJ ;
Davis, HL ;
Rosenthal, KL .
JOURNAL OF IMMUNOLOGY, 2001, 166 (05) :3451-3457
[4]   Mucosal immunity and vaccines [J].
Holmgren, J ;
Czerkinsky, C .
NATURE MEDICINE, 2005, 11 (04) :S45-S53
[5]   Mucosal immunisation and adjuvants: a brief overview of recent advances and challenges [J].
Holmgren, J ;
Czerkinsky, C ;
Eriksson, K ;
Mharandi, A .
VACCINE, 2003, 21 :S89-S95
[6]   Nalt- versus Peyer's-patch-mediated mucosal immunity [J].
Kiyono, H ;
Fukuyama, S .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (09) :699-710
[7]   Immunotherapeutic uses of CpG oligodeoxynucleotides [J].
Klinman, DM .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (04) :248-257
[8]   CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma [J].
Klinman, DM ;
Yi, AK ;
Beaucage, SL ;
Conover, J ;
Krieg, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2879-2883
[9]   Induction of specific immunoglobulin A and Th2, immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization [J].
Kodama, S ;
Suenaga, S ;
Hirano, T ;
Suzuki, M ;
Mogi, G .
INFECTION AND IMMUNITY, 2000, 68 (04) :2294-2300
[10]   CpG motifs in bacterial DNA and their immune effects [J].
Krieg, AM .
ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :709-760