TABLE 3.
EBO7 protects rhesus macaques with preexisting immunity to CAdVax against aerosolized ZEBOV challenge
| Group | Ad5 statusa | Vaccine dose (PFU)b |
ZEBOV ELISA titerc |
Clinical findingsd | Outcome [S/Te (%) or day of death] | |||
|---|---|---|---|---|---|---|---|---|
| Prime | Boost | Prime | Boost | Day 14 | ||||
| Group 1 | Immune | 1010, EBO7 | 1010, EBO7 | 2.6 | 3.8 | 5.0 | No clinical signs | 3/3 (100) |
| Group 2 | Immune | 109, EBO7 | 109, EBO7 | 2.2 | 4.0 | 4.8 | No clinical signs | 3/3 (100) |
| Group 3 | Immune | 108, EBO7 | 108, EBO7 | 1.8 | 3.0 | 4.5 | No clinical signs | 3/3 (100) |
| Control A | Naïve | 5 × 109, HC4 | D, A, widespread P, V (d7, 3.9), T, LE↑ | 9 | ||||
| Control B | Naïve | 5 × 109, HC4 | D, A, widespread P, V (d3, 2.6; d5, 4.9; d7, 5.5), T, LE↑↑↑ | 8 | ||||
| Control C | Naïve | 5 × 109, HC4 | F, D, A, moderate P, V (d5, 3.3; d7, 6.3), T, LE↑↑↑ | 7 | ||||
Immune, nine rhesus macaques were vaccinated with two doses (109 PFU) of an unrelated CAdVax vaccine approximately 1 year before the primary vaccination with EBO7.
The Ad5-immune macaques were divided into three groups and were vaccinated with EBO7. At approximately 34 weeks after the primary vaccination, macaques in groups 1 to 3 received a boosting vaccination of EBO7. At that time, control animals were vaccinated with 5 × 109 PFU of HC4. Seven days later, macaques were aerosol challenged with 800 to 1,200 PFU ZEBOV, based on back-titration.
Geometric mean titers (log10) of total serum immunoglobulin collected at various time points as measured by ELISA using inactivated ZEBOV preparations as targets. Time points: prime is at 34 weeks after the primary vaccination, on the day the macaques received a boosting vaccination of EBO7; boost is on the day of aerosol challenge; and day 14 is 14 days after challenge.
Fever (F) was defined as a rectal temperature increase of more than 2°C over baseline; depression (D) and anorexia (A) were assessed subjectively; petechia (P) was defined as mild (barely visible), moderate (visible over focal areas), or widespread; viremia (V) was defined as detectable virus in the serum, with the day (d) and log10 value in PFU/ml shown in parentheses; thrombocytopenia (T) was defined as a ≥35% decrease in platelets; and elevated levels of liver-associated enzymes (LE) were defined as a 2- to 3-fold increase (↑), a 4- to 5-fold increase (↑↑), or a more-than-5-fold increase (↑↑↑) in serum aspartate aminotransferase and alanine aminotransferase over baseline.
S/T, number of survivors/total number challenged.