Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera
Pierre Roques, … , Urban Lundberg, Andreas Meinke
Pierre Roques, … , Urban Lundberg, Andreas Meinke
Published June 14, 2022
Citation Information: JCI Insight. 2022;7(14):e160173. https://doi.org/10.1172/jci.insight.160173.
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Research Article Infectious disease Vaccines

Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera

Abstract

Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus responsible for numerous outbreaks. Chikungunya can cause debilitating acute and chronic disease. Thus, the development of a safe and effective CHIKV vaccine is an urgent global health priority. This study evaluated the effectiveness of the live-attenuated CHIKV vaccine VLA1553 against WT CHIKV infection by using passive transfer of sera from vaccinated volunteers to nonhuman primates (NHP) subsequently exposed to WT CHIKV and established a serological surrogate of protection. We demonstrated that human VLA1553 sera transferred to NHPs conferred complete protection from CHIKV viremia and fever after challenge with homologous WT CHIKV. In addition, serum transfer protected animals from other CHIKV-associated clinical symptoms and from CHIKV persistence in tissue. Based on this passive transfer study, a 50% micro–plaque reduction neutralization test titer of ≥ 150 was determined as a surrogate of protection, which was supported by analysis of samples from a seroepidemiological study. In conclusion, considering the unfeasibility of an efficacy trial due to the unpredictability and explosive, rapidly moving nature of chikungunya outbreaks, the definition of a surrogate of protection for VLA1553 is an important step toward vaccine licensure to reduce the medical burden caused by chikungunya.

Authors

Pierre Roques, Andrea Fritzer, Nathalie Dereuddre-Bosquet, Nina Wressnigg, Romana Hochreiter, Laetitia Bossevot, Quentin Pascal, Fabienne Guehenneux, Annegret Bitzer, Irena Corbic Ramljak, Roger Le Grand, Urban Lundberg, Andreas Meinke

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Figure 4

Body temperature after WT CHIKV challenge in control and VLA1553 phase I serum–treated NHPs.

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Body temperature after WT CHIKV challenge in control and VLA1553 phase I...
(A–D) Data represent mean ± SD of body temperature measured with implanted STAR ODDI chips every 2 hours for animals treated with LS d28 (in blue) and MS d28 (in green) (A), ULS d28 (in orange) and HS d28 (in pink) (B), HS d14 (in blue) and MHS d84 (in red) (C), and HS d180 (in red) and MS d180 (in brown) (D). Black lines show the control animals receiving human nonimmune serum. For all 4 panels, data for the same control animals are shown in comparison with the respective treated animals. Temperature was normalized to the night temperature (baseline on 10 consecutive nights; 10 p.m. to 6 a.m.) for each animal treated with d28 sera and to 3 consecutive nights for animals treated with d14, d84, and d180 serum as recorded chip temperature can also vary depending on animal size and exact location of the chip in the back. Temperature record from time of sampling was removed for clarity as temperature drops (around 10 a.m.) due to anesthesia were registered, except for the ones signing the serum injection (d–1) and virus exposure (d0, time 0). Remaining temperature drops in the middle of the daytime were due to nap periods. Mean ± SD were obtained from 5 animals except for 4 animals receiving LS d28 and for 3 animals receiving ULS d28 due to defective chips.