Background
Methods
Study design and participants
Vaccines
Assessment of CYD-TDV immunogenicity
Dengue antibody responses
Antibody kinetics
Blood samples
Safety assessment
Sample size and statistical methods
Results
Participants
Group 1 (N = 117) | Group 2 (N = 119) | Group 3 (N = 114) | |
---|---|---|---|
Sex, n (%) | |||
Female | 57 (48.7) | 61 (51.3) | 58 (50.9) |
Age, years | |||
Mean (SD) | 31.8 (7.7) | 32.6 (7.3) | 32.8 (7.6) |
Racial origin | |||
White Caucasian | 88 (75.2) | 103 (86.6) | 88 (77.2) |
Black or African American | 21 (17.9) | 14 (11.8) | 19 (16.7) |
Other | 8 (6.8) | 2 (1.7) | 7 (6.1) |
Seropositivity status, n (%)a | |||
Dengue seropositive | 9 (7.7) | 9 (7.6) | 8 (7.0) |
Yellow fever seropositiveb | 59 (50.4) | 61 (51.3) | 6 (5.3) |
Flavivirus seropositive | 63 (53.8) | 65 (54.6) | 11 (9.6) |
CYD-TDV immunogenicity
Impact of compressed CYD-TDV vaccination schedule
Time point | Group 1 (N = 117) | Group 2 (N = 119) | ||||
---|---|---|---|---|---|---|
n | GMT (95% CI) | Seropositive, % (95% CI) | n | GMT (95% CI) | Seropositive, % (95% CI) | |
Serotype 1 | ||||||
Baseline | 117 | 5.38 (4.85–5.96) | 1.7 (0.2–6.0) | 119 | 5.13 (4.98–5.28) | 2.5 (0.5–7.2) |
28 days post-dose 3 | 93 | 14.8 (11.3–19.4) | 52.7 (42.1–63.1) | 108 | 15.9 (12.6–20.0) | 56.5 (46.6–66.0) |
6 months post-dose 3 | 88 | 13.3 (10.2–17.4) | 47.7 (37.0–58.6) | 104 | 9.01 (7.54–10.8) | 32.7 (23.8–42.6) |
Serotype 2 | ||||||
Baseline | 117 | 5.19 (4.82–5.58) | 0.9 (0.0–4.7) | 119 | 5.22 (4.96–5.50) | 2.5 (0.5–7.2) |
28 days post-dose 3 | 94 | 51.2 (38.2–68.6) | 84.0 (75.0–90.8) | 108 | 59.9 (45.8–78.4) | 88.0 (80.3–93.4) |
6 months post-dose 3 | 88 | 45.6 (31.6–65.6) | 75.0 (64.6–83.6) | 104 | 38.7 (29.5–50.8) | 80.8 (71.9–87.8) |
Serotype 3 | ||||||
Baseline | 117 | 5.32 (4.94–5.73) | 2.6 (0.5–7.3) | 119 | 5.28 (5.03–5.55) | 4.2 (1.4–9.5) |
28 days post-dose 3 | 94 | 45.7 (35.0–59.8) | 85.1 (76.3–91.6) | 107 | 59.3 (47.0–74.7) | 90.7 (83.5–95.4) |
6 months post-dose 3 | 88 | 30.2 (22.8–40.2) | 79.5 (69.6–87.4) | 104 | 34.5 (27.5–43.3) | 80.8 (71.9–87.8) |
Serotype 4 | ||||||
Baseline | 117 | 5.78 (5.16–6.48) | 6.8 (3.0–13.0) | 119 | 5.11 (4.90–5.33) | 0.8 (0.0–4.6) |
28 days post-dose 3 | 94 | 66.8 (50.9–87.8) | 88.3 (80.0–94.0) | 107 | 83.1 (61.4–112.0) | 86.0 (77.9–91.9) |
6-months post-dose 3 | 88 | 74.8 (54.9–102.0) | 86.4 (77.4–92.8) | 104 | 41.7 (31.2–55.9) | 74.0 (64.5–82.1) |
≥ 3 serotypes | ||||||
Baseline | 117 | NA | 0.9 (0.0–4.7) | 119 | NA | 0.8 (0.0–4.6) |
28 days post-dose 3 | 94 | NA | 73.4 (63.3–82.0) | 108 | NA | 82.4 (73.9–89.1) |
6-months post-dose 3 | 88 | NA | 64.8 (53.9–74.7) | 104 | NA | 58.7 (48.6–68.2) |
All 4 serotypes | ||||||
Baseline | 117 | NA | 0.9 (0.0–4.7) | 119 | NA | 0.8 (0.0–4.6) |
Post-dose 3 | 94 | NA | 50.0 (39.5–60.5) | 108 | NA | 42.6 (33.1–52.5) |
6-months post-dose 3 | 88 | NA | 43.2 (32.7–54.2) | 104 | NA | 26.9 (18.7–36.5) |
Impact of baseline flavivirus status
Group 1 (N = 117) | Group 2 (N = 119) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
FV Seropositivea (N = 63) | FV Seronegativeb (N = 54) | FV Seropositivea (N = 65) | FV Seronegativeb (N = 54) | |||||||||
n | GMT (95% CI) | Seropositive % | n | GMT (95% CI) | Seropositive % | n | GMT (95% CI) | Seropositive % | n | GMT (95% CI) | Seropositive % | |
Serotype 1 | ||||||||||||
Baseline | 63 | 5.73 (4.72–6.94) | 3.2 (0.4–11.0) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) | 65 | 5.23 (4.96–5.53) | 4.6 (1.0–12.9) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) |
28 days post-dose 3 | 51 | 15.6 (10.6–23.0) | 54.9 (40.3–68.9) | 42 | 13.9 (9.49–20.4) | 50.0 (34.2–65.8) | 59 | 17.2 (12.7–23.3) | 61.0 (47.4–73.5) | 49 | 14.4 (10.1–20.7) | 51.0 (36.3–65.6) |
6 months post-dose 3 | 49 | 14.8 (10.0–21.7) | 53.1 (38.3–67.5) | 39 | 11.7 (8.04–17.1) | 41.0 (25.6–57.9) | 58 | 10.3 (7.85–13.4) | 36.2 (24.0–49.9) | 46 | 7.63 (6.16–9.46) | 28.3 (16.0–43.5) |
12 months post-dose 3 | NA | NA | 55 | 9.35 (7.50–11.7) | 40.0 (27.0–54.1) | 44 | 7.45 (5.87–9.47) | 25.0 (13.2–40.3) | ||||
Serotype 2 | ||||||||||||
Baseline | 63 | 5.35 (4.67–6.13) | 1.6 (0.0–8.5) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) | 65 | 5.42 (4.93–5.96) | 4.6 (1.0–12.9) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) |
28 days post-dose 3 | 52 | 60.0 (39.4–91.4) | 84.6 (71.9–93.1) | 42 | 42.1 (27.9–63.4) | 83.3 (68.6–93.0) | 59 | 68.1 (48.9–94.7) | 94.9 (85.9–98.9) | 49 | 51.4 (32.8–80.6) | 79.6 (65.7–89.8) |
6 months post-dose 3 | 49 | 52.5 (32.1–85.8) | 79.6 (65.7–89.8) | 39 | 38.1 (21.7–67.0) | 69.2 (52.4–83.0) | 58 | 53.0 (37.4–75.2) | 91.4 (81.0–97.1) | 46 | 26.0 (17.2–39.3) | 67.4 (52.0–80.5) |
12 months post-dose 3 | NA | NA | 56 | 32.7 (22.6–47.4) | 82.1 (69.6–91.1) | 44 | 22.9 (15.5–33.7) | 68.2 (52.4–81.4) | ||||
Serotype 3 | ||||||||||||
Baseline | 63 | 5.61 (4.89–6.45) | 4.8 (1.0–13.3) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) | 65 | 5.53 (5.06–6.05) | 7.7 (2.5–17.0) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) |
28 days post-dose 3 | 52 | 44.8 (31.3–64.3) | 84.6 (71.9–93.1) | 42 | 46.9 (30.9–71.2) | 85.7 (71.5–94.6) | 59 | 71.2 (53.4–94.8) | 94.9 (85.9–98.9) | 48 | 47.3 (32.5–69.0) | 85.4 (72.2–93.9) |
6 months post-dose 3 | 49 | 33.0 (23.4–46.5) | 85.7 (72.8–94.1) | 39 | 27.1 (16.6–44.3) | 71.8 (55.1–85.0) | 58 | 48.5 (36.0–65.3) | 87.9 (76.7–95.0) | 46 | 22.5 (16.3–31.0) | 71.7 (56.5–84.0) |
12 months post-dose 3 | NA | NA | 56 | 24.1 (17.6–33.0) | 73.2 (59.7–84.2) | 44 | 15.4 (11.1–21.2) | 61.4 (45.5–75.6) | ||||
Serotype 4 | ||||||||||||
Baseline | 63 | 6.55 (5.32–8.07) | 12.7 (5.6–23.5) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) | 65 | 5.20 (4.81–5.63) | 1.5 (0.0–8.3) | 54 | 5.00 (NC) | 0.0 (0.0–6.6) |
28 days post-dose 3 | 52 | 51.7 (35.1–76.2) | 82.7 (69.7–91.8) | 42 | 91.8 (63.3–133) | 95.2 (83.8–99.4) | 59 | 78.5 (54.3–114) | 88.1 (77.1–95.1) | 48 | 89.2 (53.3–149) | 83.3 (69.8–92.5) |
6 months post-dose 3 | 49 | 60.0 (38.4–93.8) | 81.6 (68.0–91.2) | 39 | 98.7 (64.8–150) | 92.3 (79.1–98.4) | 58 | 39.8 (26.9–59.0) | 70.7 (57.3–81.9) | 46 | 44.3 (28.3–69.5) | 78.3 (63.6–89.1) |
12 months post-dose 3 | NA | NA | 56 | 46.9 (32.2–68.4) | 80.4 (67.6–89.8) | 44 | 48.7 (30.5–77.5) | 81.8 (67.3–91.8) |
Impact of YF vaccine co-administration
Time point | Group 1 and 2 pooled, YF− (n = 116) | Group 3, YF− (n = 108) | ||||
---|---|---|---|---|---|---|
n | GMT (95% CI) | Seropositive, % (95% CI) | n | GMT (95% CI) | Seropositive, % (95% CI) | |
Serotype 1 | ||||||
Baseline | 116 | 5.19 (4.87–5.53) | 1.7 (0.2–6.1) | 108 | 5.00 (NC) | 0 (0.0–3.4) |
Post-dose 1 | 116 | 8.71 (7.04–10.8) | 23.3 (15.9–32.0) | 108 | 7.68 (6.46–9.14) | 20.4 (13.2–29.2) |
Serotype 2 | ||||||
Baseline | 116 | 5.06 (4.94–5.19) | 0.9 (0.0–4.7) | 108 | 5.06 (4.94–5.20) | 0.9 (0.0–5.1) |
Post-dose 1 | 116 | 18.8 (13.9–25.3) | 46.6 (37.2–56.0) | 108 | 10.8 (8.63–13.4) | 35.2 (26.2–45.0) |
Serotype 3 | ||||||
Baseline | 116 | 5.21 (4.97–5.47) | 2.6 (0.5–7.4) | 108 | 5.28 (4.90–5.69) | 2.8 (0.6–7.9) |
Post-dose 1 | 114 | 28.5 (20.4–39.7) | 57.9 (48.3–67.1) | 108 | 8.88 (7.23–10.9) | 25.0 (17.2–34.3) |
Serotype 4 | ||||||
Baseline | 116 | 5.43 (4.99–5.92) | 3.4 (0.9–8.6) | 108 | 5.26 (4.90–5.65) | 1.9 (0.2–6.5) |
Post-dose 1 | 114 | 229 (139–378) | 74.6 (65.6–82.3) | 107 | 22.6 (15.9–32.3) | 48.6 (38.8–58.5) |
Group 1 (N = 120) | Group 2 (N = 120) | Group 3 (N = 119) | ||||
---|---|---|---|---|---|---|
n/M | % (95% CI) | n/M | % (95% CI) | n/M | % (95% CI) | |
First CYD-TDV dose | ||||||
Solicited reaction | 75/118 | 63.6 (54.2–72.2) | 77/119 | 64.7 (55.4–73.2) | 87/115 | 75.7 (66.8–83.2) |
Solicited injection site reactiona | 34/118 | 28.8 (20.8–37.9) | 42/118 | 35.3 (26.8–44.6) | 40/115 | 34.8 (26.1–44.2) |
Solicited systemic reaction | 65/118 | 55.1 (45.7–64.3) | 68/118 | 57.1 (47.7–66.2) | 77/115 | 67.0 (57.6–75.4) |
Unsolicited non-serious AE | 34/120 | 28.3 (20.5–37.3) | 32/120 | 26.7 (19.0–35.5) | 27/119 | 22.7 (15.5–31.3) |
Unsolicited non-serious AR | 7/120 | 5.8 (2.4–11.6) | 4/120 | 3.3 (0.9–8.3) | 9/119 | 7.6 (3.5–13.9) |
Unsolicited non-serious injection site ARa | 4/120 | 3.3 (0.9–8.3) | 3/120 | 2.5 (0.5–7.1) | 0/119 | 0.0 (0.0–3.1) |
Unsolicited non-serious systemic AE | 31/120 | 25.8 (18.3–34.6) | 30/120 | 25.0 (17.5–33.7) | 25/119 | 21.0 (14.1–29.4) |
Unsolicited non-serious systemic AR | 3/120 | 2.5 (0.5–7.1) | 2/120 | 1.7 (0.2–5.9) | 7/119 | 5.9 (2.4–11.7) |
Second CYD-TDV dose | ||||||
Solicited reaction | 44/101 | 43.6 (33.7–53.8) | 57/114 | 50.0 (40.5–59.5) | 40/96 | 41.7 (31.7–52.2) |
Solicited injection site reaction | 21/101 | 20.8 (13.4–30.0) | 32/114 | 28.1 (20.1–37.3) | 24/96 | 25.0 (16.7–34.9) |
Solicited systemic reaction | 38/101 | 37.6 (28.2–47.8) | 43/114 | 37.7 (28.8–47.3) | 33/96 | 34.4 (25.0–44.8) |
Unsolicited non-serious AE | 15/105 | 14.3 (8.2–22.5) | 18/116 | 15.5 (9.5–23.4) | 15/108 | 13.9 (8.0–21.9) |
Unsolicited non-serious AR | 3/105 | 2.9 (0.6–8.1) | 2/116 | 1.7 (0.2–6.1) | 0/108 | 0.0 (0.0–3.4) |
Unsolicited non-serious injection site AR | 1/105 | 1.0 (0.0–5.2) | 1/116 | 0.9 (0.0–4.7) | 0/108 | 0.0 (0.0–3.4) |
Unsolicited non-serious systemic AE | 15/105 | 14.3 (8.2–22.5) | 18/116 | 15.5 (9.5–23.4) | 15/108 | 13.9 (8.0–21.9) |
Unsolicited non-serious systemic AR | 2/105 | 1.9 (0.2–6.7) | 1/116 | 0.9 (0.0–4.7) | 0/108 | 0.0 (0.0–3.4) |
Third CYD-TDV dose | ||||||
Solicited reaction | 36/91 | 39.6 (29.5–50.4) | 47/107 | 43.9 (34.3–53.9) | 37/89 | 41.6 (31.2–52.5) |
Solicited injection site reaction | 19/91 | 20.9 (13.1–30.7) | 29/106 | 27.4 (19.1–36.9) | 21/89 | 23.6 (15.2–33.8) |
Solicited systemic reaction | 32/91 | 35.2 (25.4–45.9) | 39/107 | 36.4 (27.4–46.3) | 32/89 | 36.0 (26.1–46.8) |
Unsolicited non-serious AE | 19/98 | 19.4 (12.1–28.6) | 17/110 | 15.5 (9.3–23.6) | 13/95 | 13.7 (7.5–22.3) |
Unsolicited non-serious AR | 2/98 | 2.0 (0.2–7.2) | 0/110 | 0.0 (0.0–3.3) | 1/95 | 1.1 (0.0–5.7) |
Unsolicited non-serious injection site AR | 2/98 | 2.0 (0.2–7.2) | 0/110 | 0.0 (0.0–3.3) | 0/95 | 0.0 (0.0–3.8) |
Unsolicited non-serious systemic AE | 17/98 | 17.3 (10.4–26.3) | 17/110 | 15.5 (9.3–23.6) | 13/95 | 13.7 (7.5–22.3) |
Unsolicited non-serious systemic AR | 0/98 | 0.0 (0.0–3.7) | 0/110 | 0.0 (0.0–3.3) | 1/95 | 1.1 (0.0–5.7) |