TY - JOUR
T1 - Development of safer pertussis DNA vaccine expressing non-toxic C180 polypeptide of pertussis toxin S1 subunit
AU - Kamachi, Kazunari
AU - Arakawa, Yoshichika
PY - 2007/1/22
Y1 - 2007/1/22
N2 - A toxic N-terminal 180-amino-acid fragment (C180) of pertussis toxin S1 subunit has the most potent ability to induce protective immunity against pertussis toxin (PT) following DNA-based immunization [Kamachi K, Arakawa Y. Infect Immun 2004;72:4293-6]. For the development of a safer pertussis DNA vaccine, three plasmids encoding mutant C180 (C180-R9K, C180-E129G and C180-R9K/E129G) were constructed and tested for their protective immunogenicity and cytotoxicity. All of the gene gun delivery of the plasmid, performed by inserting the mutant C180 gene into a mammalian expression vector pcDNA3.1, successfully induced anti-PT IgG antibody production without the loss of immunogenicity in mice. The immunizations of mice with the plasmids significantly inhibited leukocytosis-promoting activity by PT. Among stably transfected Chinese hamster ovary (CHO) cells expressing mutant C180, the expression of C180-R9K and C180-R9K/E129G was non-toxic to the transfectants, confirming that these mutant C180s have no cytotoxicity to mammalian cells. These results indicate that C180-R9K and C180-R9K/E129G genes, especially C180-R9K/E129G, are candidates for safe and effective antigen DNAs in the development of pertussis DNA vaccine.
AB - A toxic N-terminal 180-amino-acid fragment (C180) of pertussis toxin S1 subunit has the most potent ability to induce protective immunity against pertussis toxin (PT) following DNA-based immunization [Kamachi K, Arakawa Y. Infect Immun 2004;72:4293-6]. For the development of a safer pertussis DNA vaccine, three plasmids encoding mutant C180 (C180-R9K, C180-E129G and C180-R9K/E129G) were constructed and tested for their protective immunogenicity and cytotoxicity. All of the gene gun delivery of the plasmid, performed by inserting the mutant C180 gene into a mammalian expression vector pcDNA3.1, successfully induced anti-PT IgG antibody production without the loss of immunogenicity in mice. The immunizations of mice with the plasmids significantly inhibited leukocytosis-promoting activity by PT. Among stably transfected Chinese hamster ovary (CHO) cells expressing mutant C180, the expression of C180-R9K and C180-R9K/E129G was non-toxic to the transfectants, confirming that these mutant C180s have no cytotoxicity to mammalian cells. These results indicate that C180-R9K and C180-R9K/E129G genes, especially C180-R9K/E129G, are candidates for safe and effective antigen DNAs in the development of pertussis DNA vaccine.
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U2 - 10.1016/j.vaccine.2006.09.077
DO - 10.1016/j.vaccine.2006.09.077
M3 - Article
C2 - 17050047
AN - SCOPUS:33845579908
SN - 0264-410X
VL - 25
SP - 1000
EP - 1006
JO - Vaccine
JF - Vaccine
IS - 6
ER -