Cross-neutralizing activity of the chikungunya vaccine VLA1553 against three prevalent chikungunya lineages

Abstract

Cross-neutralization is generally a prerequisite for cross-protection of vaccines against diseases caused by heterologous viruses. Using sera obtained from a randomized clinical phase 3 trial in adults, we investigated the cross-neutralization activity of VLA1553, a vaccine recently approved to prevent chikungunya disease. Analysed in a plaque reduction neutralization test, the three major chikungunya virus (CHIKV) lineages, namely the East Central South African, the West African, and the Asian lineage, were inhibited by CHIKV-specific neutralizing antibodies present in the sera from vaccinated humans. This effect was independent of the time elapsed since vaccination. Moreover, the magnitude of the immune response was similar to the antibody levels detected in sera from convalescent chikungunya patients. Thus, VLA1553 has the potential to diminish the burden of chikungunya disease on a global scale.Trial registration: ClinicalTrials.gov identifier: NCT04546724.

Keywords: CHIKV lineages; Chikungunya virus; VLA1553; cross-neutralization; vaccine.

Figure 1.

Cross-neutralization titres over time after vaccination with VLA1553. A, B, C: comparison of PRNT50 titres of the three investigated CHIKV lineages ECSA (strain LR2006_OPY1), West-African (strain WA_37997), and Asian (Caribbean_clone M109); D: corresponding µPRNT50 titres (strain: TSI-GSD-218) from the phase 3 clinical trial; only participants seronegative at baseline were included; data from vaccine sera are represented as GMT with 95% CI; limit of detection: PRNT50 = 10; all results below 10 were imputed as PRNT50 = 5 in the data set. limit of detection: µPRNT50 = 20.

Figure 2.

Absence of anamnestic response after vaccination with VLA1553. PRNT50 titres were analysed in samples from baseline positive participants with three CHIKV lineages: ECSA (strain LR2006_OPY1), West-African (strain WA_37997), and Asian (Caribbean_clone M109); data are represented as individual dots per sample and bars show the GMT; limit of detection: PRNT50 = 10.

Figure 3.

Comparison of PRNT50 titres from post-vaccination and convalescent sera. Neutralization titres from samples of baseline seropositive participants previously exposed to CHIKV (convalescent sera collected at day 1; n=5) and serum from individuals seronegative at baseline (post-vaccination sera collected at day 29; n=27) were analysed with three CHIKV lineages: ECSA (strain LR2006_OPY1), West-African (strain WA_37997), and Asian (Caribbean_clone M109). Data are represented as individual dots per sample and bars show the GMT with 95% CI; limit of detection: PRNT50 = 10; all results below 10 were imputed as PRNT50 = 5 in the data set.