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Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus
Pierre Roques, … , Roger Le Grand, Peter Liljeström
Pierre Roques, … , Roger Le Grand, Peter Liljeström
Published March 23, 2017
Citation Information: JCI Insight. 2017;2(6):e83527. https://doi.org/10.1172/jci.insight.83527.
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Research Article Infectious disease Vaccines

Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

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Abstract

Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this virus is a serious threat to public health, but at present, there is no vaccine against this debilitating disease. We have recently developed a number of vaccine candidates, and here we have evaluated 3 of them in a nonhuman primate model. A single immunization with an attenuated strain of CHIKV (Δ5nsP3), a homologous prime-boost immunization with a DNA-launched RNA replicon encoding CHIKV envelope proteins (DREP-E), and a DREP-E prime followed by a recombinant modified vaccinia virus Ankara encoding CHIKV capsid and envelope (MVA-CE) boost all induced protection against WT CHIKV infection. The attenuated Δ5nsP3 virus proved to be safe and did not show any clinical signs typically associated with WT CHIKV infections such as fever, skin rash, lymphopenia, or joint swelling. These vaccines are based on an East/Central/South African strain of Indian Ocean lineage, but they also generated neutralizing antibodies against an isolate of the Asian genotype that now is rapidly spreading across the Americas. These results form the basis for clinical development of an efficacious CHIKV vaccine that generates both humoral and cellular immunity with long-term immunological memory.

Authors

Pierre Roques, Karl Ljungberg, Beate M. Kümmerer, Leslie Gosse, Nathalie Dereuddre-Bosquet, Nicolas Tchitchek, David Hallengärd, Juan García-Arriaza, Andreas Meinke, Mariano Esteban, Andres Merits, Roger Le Grand, Peter Liljeström

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Figure 1

CHIKV vaccines and immunizations.

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CHIKV vaccines and immunizations.
(A) Vaccine constructs are based on th...
(A) Vaccine constructs are based on the LR-CHIKV strain LR-2006OPY1. Top, Δ5nsP3, (Δ5), an infectious attenuated virus carrying a 60 amino acid–long deletion in the nsP3 replicase protein (9). Middle, the DREP-E (D) replicon DNA vaccine (9). Bottom, the recombinant modified vaccinia virus Ankara MVA-CE (M) vaccine (8) has a cDNA copy of the CHIKV structural gene cassette (C-E3-E2-6K-E1) inserted into the MVA genome and is expressed under the control of the MVA sE/L promoter. (B) Immunization schedule of cynomolgus macaques. Group Δ5nsP3-A received one s.c. injection of 1 × 105 PFU of Δ5 virus on day 42 (red arrow). Group Δ5nsP3-B received one s.c. injection of 1 × 105 PFU of Δ5 virus on day 0 (red arrow). Group DREP-E received 200 μg of D by intradermal (i.d.) injection followed by electroporation (EP) on days 0 and 42 (green arrows). Group DREP-E+MVA-CE was primed on day 0 with 200 μg of D followed by an i.m. injection of 1 × 108 PFU of M on day 42 (blue arrows). Group 4 (controls) received 0.9% NaCl injections i.d. followed by EP on day 0 and s.c, i.m., and i.d. injections followed by EP on day 42 (orange arrows). All animals were challenged with 100 animal infectious doses 50% (AID50) WT LR-CHIKV on day 123 for groups 1A, 2, 3, and 4 and on day 294 for group 1B (black arrows). The study ended on day 298 for all groups except group 1B, which ended on day 359.

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