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 6

Viremia in macaques following challenge with WT LR-CHIKV (vaccine study) or infection with Δ5 virus (safety study).

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Viremia in macaques following challenge with WT LR-CHIKV (vaccine study)...
(A) Plasma viremia of vaccinated animals after challenge. Vaccinated animals (groups Δ5, DD, DM) or control animals that had received saline only (group 4) were challenged with 100 50% animal infections dose (AID50) (about 7,000–10,000 PFU) of WT LR-CHIKV. Only the control group (NaCl, orange squares) displayed any viremia. The groups Δ5 (red circle), DD (green square), and DM (blue triangle) did not display any viremia. (B) Plasma viremia of naive animals infected with 1 × 105 PFU of the Δ5 virus (group Δ5-B in Figure 1). Animals shown in red (n = 4) were infected by inoculating the virus s.c. in the back, whereas animals inoculated s.c. in the wrist (SCw) (n = 2) are indicated in purple. (C) Comparison of mean viremia + SEM in LR-CHIKV (WT CHIKV) challenged control animals (from A) with mean viremia + SEM in Δ5 infected animals (from B). The viremia from WT and Δ5 differ significantly at the time point indicated (****P < 0.0001; 2-way ANOVA + Bonferroni’s multiple comparisons test). (D) Total viral production in LR-CHIKV challenged control animals and Δ5 infected animals. AUC were computed using trapezoid rules taking in account a baseline setup at the limit of quantitation of the qPCR we used (100 copies/ml = 2 in Log10). Statistics was done using Mann & Whitney U test.