Table 1.
Summary of single- and repeated-dose toxicity studies in Jcl:SD rats.
|
Group 1 High dose (100 µg) |
Group 2 Medium dose (50 µg) |
Group 3 Low dose (25 µg) |
Group 4 Active control (Adjuvant) | Group 5 Negative control (PBS) | |
|---|---|---|---|---|---|
| Single dose |
n = 10 (M/F) Immunization: day 0 Euthanized: day 15 |
NA | NA | NA |
n = 10 (M/F) Immunization: day 0 Euthanized: day 15 |
| Mortality | None observed | NA | NA | NA | None observed |
| Clinical sign observation | None | NA | NA | NA | None |
| Body temperature | No significant changes | NA | NA | NA | No changes |
| Body weights | No significant changes | NA | NA | NA | No changes |
| Food consumption | No vaccine-related effect | NA | NA | NA | No changes |
| Water consumption | No vaccine-related effect | NA | NA | NA | No changes |
| Gross examination | No vaccine-related macroscopic findings | NA | NA | NA | No changes |
| Repeated dose |
n = 40 (M/F) Immunization: days 0, 21, 42 Interim analysis n = 10 (M/F) Euthanized: day 3 Main Study n = 20 (M/F) Euthanized: day 45 Recovery Study n = 10 (M/F) Euthanized: day 64 |
Main Study n = 20 (M/F) Immunization: days 0, 21, 42 Euthanized: day 45 |
Main Study n = 20 (M/F) Immunization: days 0, 21, 42 Euthanized: day 45 |
n = 40 (M/F) Immunization: days 0, 21, 42 Interim analysis n = 10 (M/F) Euthanized: day 3 Main Study n = 20 (M/F) Euthanized: day 45 Recovery Study n = 10 (M/F) Euthanized: day 64 |
n = 40 (M/F) Immunization: days 0, 21, 42 Interim analysis n = 10 (M/F) Euthanized: day 3 Main Study n = 20 (M/F) Euthanized: day 45 Recovery Study n = 10 (M/F) Euthanized: day 64 |
| Mortality | None observed | None observed | None observed | None observed | None observed |
| Clinical sign observation | No significant changes | No significant changes | None | None | None |
| Local tolerance |
Erythema formation After first immunization: 2/40 (day 0–2)After second immunization: 8/30 (day 21–23) Edema formation After second immunization: 5/30 (day 21–24) |
Erythema formation After first immunization: 1/20 (day 0–3) |
Erythema formation After first immunization: 6/20 (day 0–2)After second immunization: 7/20 (day 21–24) Edema formationAfter first immunization: 1/20 (day 0–1) |
Erythema formation After second immunization: 2/30 (day 21–23) Edema formation After second immunization: 1/30 (day 23) |
Erythema formation After first immunization: 2/40 rats (day 2–3)After second immunization: 3/30 rats (day 23) Edema formation After first immunization: 1/40 rat (day 3) |
| Body temperature | No vaccine-related effect | No vaccine-related effect | No vaccine-related effect | No adjuvant-related effect | No changes |
| Body weights | No vaccine-related effect | No vaccine-related effect | No vaccine-related effect | No adjuvant-related effect | No changes |
| Food consumption | No vaccine-related effect | No vaccine-related effect | No vaccine-related effect | No adjuvant-related effect | No changes |
| Water consumption | No vaccine-related effect | No vaccine-related effect | No vaccine-related effect | No adjuvant-related effect | No changes |
M: Male, F: Female; NA: Not Applicable.