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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

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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 3

Peak viremia titers plotted against μPRNT50 titers.

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Peak viremia titers plotted against μPRNT50 titers.
The μPRNT50 titers o...
The μPRNT50 titers of the control NHPs receiving nonimmune serum were all negative (<10; Supplemental Table 1) and were, therefore, imputed to 5. Undetectable viremia titers were imputed to 10. Filled symbols denote VLA1553 phase I sera at d28; unfilled symbols denote sera obtained at d14, d84, and d180 after vaccination. For HS d28, 2 data points have identical μPRNT50 titers with undetectable RNA; they are, thus, represented by 1 data point. Horizontal red dotted lines show LLOQ (500 copies/mL) and LLOD (60 copies/mL) of the qPCR. Vertical red dotted lines show μPRNT50 titers of 50 and 100, while the vertical solid line shows the μPRNT50 titer of 150. ULS, ultra-low titer serum; LS, low titer serum; MHS, medium high titer serum; MS, medium titer serum; and HS, high titer serum.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

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