Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial.
2017 08 24
Journal Article
Authors:
Mulligan, M.J.;
Stapleton, J.T.;
Keitel, W.A.;
Frey, S.E.;
Chen, W.H.;
Rouphael, N.;
Edupuganti, S.;
Beck, A.;
Winokur, P.L.;
Sahly, H.M.El;
Patel, S.M.;
Atmar, R.L.;
Graham, I.;
Anderson, E.;
El-Kamary, S.S.;
Pasetti, M.F.;
Sztein, M.B.;
Hill, H.;
Goll, J.B.
Secondary:
Vaccine
Volume:
35
Pagination:
4730-4737
Issue:
36
PMID:
28750854
DOI:
10.1016/j.vaccine.2017.07.024
Keywords:
Adolescent; Adult; Agglutination Tests; Antibodies, Bacterial; Bacterial Vaccines; Double-Blind Method; Female; Francisella tularensis; Humans; Male; Middle Aged; Seroconversion; Tularemia; Vaccination; Vaccines, Attenuated; Young Adult
Abstract:
BACKGROUND: Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices.METHODS: A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180.PRINCIPAL RESULTS: Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was -6.9% (-16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001).MAJOR CONCLUSIONS: The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695.
