Journal
VACCINE
Volume 38, Issue 3, Pages 644-654Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2019.10.049
Keywords
Smallpox; TPDXX (R); ACAM2000; Biodefense; Tecovirimat; ST-246 (R); Monkeypox virus; Vaccinia; Variola; Antiviral; Animal Rule
Categories
Funding
- National Institute of Allergy and Infectious Diseases at the National Institutes of Health [N01-AI-30063]
- SBIR/STTR Phase 2 Grant [5R44AI075747]
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Naturally occurring smallpox has been eradicated but research stocks of variola virus (VARV), the causative agent of smallpox, still exist in secure laboratories. Clandestine stores of the virus or resurrection of VARV via synthetic biology are possible and have led to concerns that VARV could be used as a biological weapon. The US government has prepared for such an event by stockpiling smallpox vaccines and TPDXX (R), SIGA Technologies' smallpox antiviral drug. While vaccination is effective as a pre-exposure prophylaxis, protection is limited when administered following exposure. Safety concerns preclude general use of the vaccine unless there is a smallpox outbreak. TPDXX is approved by the FDA for use after confirmed diagnosis of smallpox disease. Tecovirimat, the active pharmaceutical ingredient in TPDXX, targets a highly conserved orthopoxviral protein, inhibiting long-range dissemination of virus. Although indications for use of the vaccine and TPDXX do not overlap, concomitant use is possible, especially if the TPDXX indication is expanded to include post-exposure prophylaxis. It is therefore important to understand how vaccine and TPDXX may interact. In studies presented here, monkeys were vaccinated with the ACAM2000 (TM) live attenuated smallpox vaccine and concomitantly treated with tecovirimat or placebo. Immune responses to the vaccine and protective efficacy versus a lethal monkeypox virus (MPXV) challenge were evaluated. In two studies, primary and anamnestic humoral immune responses were similar regardless of tecovirimat treatment while the third study showed reduction in vaccine elicited humoral immunity. Following lethal MPXV challenge, all (12 of 12) vaccinated/placebo treated animals survived, and 12 of 13 vaccinated/tecovirimat treated animals survived. Clinical signs of disease were elevated in tecovirimat treated animals compared to placebo treated animals. This suggests that TPDXX may affect the immunogenicity of ACAM2000 if administered concomitantly. These studies may inform on how vaccine and TPDXX are used during a smallpox outbreak. (C) 2019 The Authors. Published by Elsevier Ltd.
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