A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.
Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.
Sugai
Toshiyuki
T
Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. toshi211@med.yokohama-cu.ac.jp
Mori
Masaaki
M
Nakazawa
Masatoshi
M
Ichino
Motohide
M
Naruto
Takuya
T
Kobayashi
Naoki
N
Kobayashi
Yoshinori
Y
Minami
Mutsuhiko
M
Yokota
Shumpei
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D018899:CpG Islands; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000517:prevention & control; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007441:Intubation, Gastrointestinal; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D007074:Immunoglobulin G; D009841:Oligonucleotides; C041524:aluminum sulfate; D010047:Ovalbumin