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Infections with the chikungunya virus are increasingly reported due to many reasons including climate change. Two vaccines against chikungunya have recently been approved in Europe, the live-attenuated vaccine (LAV) Ixchiq and the virus like particle (VLP) vaccine Vimkunya. However, no systematic review of phase 3 clinical trial data has been published that summarizes the currently available evidence on the immunogenicity, tolerability, and safety of these vaccines. Therefore, these data were systematically analyzed by a working group of the German Standing Committee on Vaccination (STIKO) and the German Society for Tropical Medicine, Travel Medicine and Global Health (DTG). We conducted a systematic review of the immunogenicity, tolerability and safety of Ixchiq and Vimkunya using Embase and PubMed (OVID) according to predefined PICO criteria, including placebo-controlled randomized control trials, cohort, and case-control studies. Risk of bias (RoB) was assessed with the RoB 2-tool. Additionally, post-marketing safety data were studied. Clinical efficacy data were not available. Instead, seropositivity rates above a predefined threshold served as a surrogate of protection. Both vaccines demonstrated strong immunogenicity with seroprotection rates for Ixchiq of >98% after 4 weeks, and for Vimkunya after 3 weeks of >97% in 12–59-year-olds and > 87% in ≥65-year-olds. In the pivotal studies, both vaccines showed also an acceptable safety profile. Post-marketing safety data showed a higher risk for serious adverse events in elderly patients for Ixchiq. In addition to mosquito protection and vector control, two vaccines with a good efficacy profile based on the surrogate marker of seroprotection are now available to prevent chikungunya. While both vaccines showed acceptable tolerability, the safety of vaccines must be continuously assessed based on further data from post-marketing surveillance of the respective populations.

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O’nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8–9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout.

Recent epidemics of dengue and chikungunya have highlighted the urgent need for vaccines to reduce the risk of infection in travellers. Given challenges with tracking chikungunya outbreaks in real-time and the widespread resurgence of dengue, broader indications for the use of the new chikungunya and dengue vaccines should be considered.

Abstract Background Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV). Methods Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18 years in two Phase 3 trials [N = 656 participants (per protocol analysis set)]. Immunogenicity data to 180 days post-vaccination [geometric mean titres (GMTs), seroresponse rate, seroconversion rate] were pooled for the two trials. A comparison of subgroups based on age, sex, body mass index (BMI), race and baseline seropositivity was included. All analyses were descriptive. Results Most participants were aged 18–64 years (N = 569/656 [86.7%]), there were slightly more females (N = 372/656 [56.7%]), most were not Hispanic/Latino (N = 579/656 [88.3%]), and most were White (N = 517/656 [78.8%]). In baseline seronegative participants, GMT peaked at Day 29 post-vaccination, and subsequently declined slightly but remained elevated until Day 180. At Days 29, 85 and 180, seroresponse rate was 98.3, 97.7 and 96.4% and seroconversion rate was 98.5, 98.4 and 98.2%. There were no differences in seroresponse rate in participants aged 18–64 years or ≥65 years at Day 29 (98.1 vs 100%), Day 85 (97.4 vs 100%) and Day 180 (96.3 vs 96.5%) nor based on sex, BMI, ethnicity or race. An immune response was shown in a small heterogenous population of baseline seropositive participants, with GMTs showing the same trend as baseline seronegative participants. Conclusions A single dose of VLA1553 elicited a very strong immune response by Day 29 that remained elevated at Day 180 in both baseline seronegative and seropositive participants in a combined evaluation of two Phase 3 trials. The vaccine was similarly immunogenic in participants aged ≥65 years and 18–64 years, and there were no differences based on subgroup analyses for sex, BMI, ethnicity or race.

In 2024-2025, Réunion Island experienced a large outbreak driven by East-Central-South African (ECSA)-2 lineage of chikungunya virus (CHIKV), leading to the implementation of a vaccination campaign using live-attenuated IXCHIQ (VLA1553). Currently, distinguishing vaccine-derived viremia from wild-type infection relies on genomic sequencing, which is resource-intensive and not routinely available in many diagnostic laboratories. To address this gap, we developed a duplex real-time RT-qPCR assay specifically designed to differentiate VLA1553 from wild-type ECSA strains circulating in La Réunion. The assay targets the non-structural protein 3 hypervariable region, including the 61-amino-acid deletion characteristic of the VLA1553 backbone. Analytical performance was assessed using a panel of CHIKV isolates representing different lineages and a VLA1553-like strain generated using an Infectious Subgenomic Amplicon system. Clinical performance was evaluated using samples from recently vaccinated individuals and patients infected with ECSA-2 strains, and compared with two RT-qPCR assays routinely used by the French National Reference Centers for arboviruses. The duplex assay proved to be specific, detecting wild-type ECSA strains exclusively in the FAM channel and the vaccine strain exclusively in the HEX channel, with no cross-reactivity. It demonstrated high sensitivity, with LOD95 values of 0.9 and 1.1 copies/µL for the vaccine-specific and wild-type-specific targets, respectively. All clinical samples were correctly classified, including one vaccinated individual simultaneously infected with a circulating wild-type strain, as confirmed by sequencing. This duplex assay provides a rapid and reliable method to distinguish vaccine-derived from naturally-acquired CHIKV viremia, supporting more accurate clinical and epidemiological investigations in settings where vaccination and viral circulation overlap.

Background Chikungunya virus (CHIKV) is a mosquito-transmitted, arthritogenic alphavirus that causes sporadic outbreaks of often debilitating rheumatic disease. The recently approved CHIKV vaccine, IXCHIQ, is based on a live-attenuated CHIKV strain (VLA1553), with viraemic vaccine recipients theoretically able to transmit VLA1553 to mosquitoes with ensuing onward transmission. We thus evaluated VLA1553 transmission from artificial blood meals to Aedes albopictus mosquitoes, and onward transmission to mice. Methods Female A. albopictus mosquitoes were fed on defibrinated sheep blood containing wild-type CHIKV (viral titre: 7.50 log 10 CCID 50 /mL) or VLA1553 (viral titres: 7.85, 5.72, 4.58, and 3.79 log 10 CCID 50 /mL). Viral titres in mosquito bodies and saliva were determined using CCID 50 assays 7–8 days after the blood meal. After providing CHIKV or VLA1553 (viral titres ~ 7–8 log 10 CCID 50 /mL) in blood meals to mosquitoes, infected mosquitoes were fed on highly susceptible Irf3/7 −/− mice ( n  = 3 per group). Data were re-analysed using the same reverse transcription quantitative polymerase chain reaction (RT-qPCR) as for an earlier VLA1553 phase 1 clinical trial, to allow correlations between blood meal titres and viraemia in vaccine recipients. Results Mosquito body viral titres were significantly higher ( P  < 0.0001) for CHIKV versus VLA1553-fed mosquitoes at blood meal viral titres of ~ 7–8 log 10 CCID 50 /mL. Mosquito body VLA1553 titres decreased with reducing blood meal titres, but there was no dose-dependent effect on saliva viral titres. No dissemination to salivary glands was seen at blood meal titres ≤ 3.875 log 10 CCID 50 /mL. CHIKV-fed mosquitoes were able to transmit virus, and induce viraemia in, 3/3 Irf3/7 −/− mice via mosquito bites. In contrast, 0/3 Irf3/7 −/− mice became infected after bites from VLA1553-fed mosquitoes. RT-qPCR comparisons with phase 1 clinical data for VLA1553-vaccinated individuals indicated that VLA1553 viraemia was at or below the aforementioned threshold for transmission. Conclusions The evidence presented herein argue that the low viraemia in VLA1553-vaccinated individuals would mitigate against transmission. In addition, replication of VLA1553 in mosquito bodies was also significantly attenuated. Overall, mosquito-borne transmission of VLA1553 from vaccinated individuals to others appears improbable. Graphical Abstract

Keywords: chikungunya, CHIKV vaccine, Ixchiq, alphavirus, Pakistan

Chikungunya is a febrile illness caused by an arbovirus transmitted by Aedes spp. mosquitoes, which are abundant worldwide and can easily establish new habitats. With urbanization and climate change, the vector has spread to new areas. Chikungunya has caused multiple outbreaks worldwide in most continents. Molecular evidence suggests that a single mutation in the chikungunya virus can influence vector specificity, enhancing its potential to cause explosive outbreaks. The infection commonly presents with a triad of fever, rash, and arthritis. The latter symptom occurs in more than 90% of sufferers and may persist for many months to years, causing significant morbidity. Currently, no antiviral therapy is available, and management is primarily supportive. Several cases of Chikungunya acquired through international travel have been reported. Travel-associated viremic cases can drive introduction and local transmission in new geographical areas where the mosquito vector is abundant. Awareness of the disease among both travelers and healthcare providers remains poor. A global one health approach, with strengthened public health policies, enhanced surveillance, and travel-related prevention, is currently the most effective way to curb the reemerging threat of the disease. Two vaccines are currently available and are durable for at least 2 years; though they lack efficacy data, they have both been approved. First, VLA1553, trade-named IXCHIQ, is a live-attenuated vaccine with nearly 99% seroprotection; however, it has many safety concerns, including Chikungunya-like illness (CLI), and has recently been paused for use in persons older than 60 years. Second, PXVX0317, trade-named Vimkunya, is a virus-like particle with nearly 98% seroprotection, but it does not cause CLI. Both vaccines are currently recommended for travelers visiting areas with a CDC-declared outbreak.