Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus
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
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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Research Article Infectious disease Vaccines

Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

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 4

CHIKV-specific T cell responses induced by CHIKV vaccine candidates.

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CHIKV-specific T cell responses induced by CHIKV vaccine candidates. Δ5,...
Δ5, attenuated virus (n = 6) (red); DD, homologous prime-boost (n = 4) (green); DM, heterologous prime-boost (n = 6) (blue); Control, no vaccine but NaCl injection only (n = 4) (orange). Panels compare the sum of IFN-γ T cell responses from each group measured by FluoroSpot assays on PBMC collected at 14 days after boost (A), 7 days before challenge (B), and 7 days after challenge (C) and stimulated with envelope E1 and E2, Capsid, and nsP1 peptide pools. Statistical comparisons were performed at 14 days after boost, 7 days prechallenge, and 7 days after challenge. Panel D compares cumulated IFN-γ responses against all peptides for each group (mean ± SEM). Animals were immunized on days 0 and/or 42 (y axis and black vertical dotted line) and challenged on day 123 (red vertical dotted line). CHIKV-specific IFN-γ T cells responses against E1 (E, G, I) and E2 (F, H, J) peptide pools at 14 days after boost (E and F), 7 days before challenge (G and H), and 7 days after challenge (I and J). Panels show IFN-γ responses in individual animals with mean (± SEM). For statistical analyses, the Kruskal-Wallis test followed by the Mann-Whitney U test were used to identify differences between groups. Significance is represented by *P < 0.05 or **P < 0.01; 95% CI.