Chikungunya vaccine (live) powder and solvent for solution for injection 0.5ml vials

BackgroundVLA1553 is a live-attenuated vaccine candidate for active immunisation and prevention of disease caused by chikungunya virus. We report safety and immunogenicity data up to day 180 after vaccination with VLA1553.MethodsThis double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA. Eligible participants were healthy volunteers aged 18 years and older. Patients were excluded if they had history of chikungunya virus infection or immune-mediated or chronic arthritis or arthralgia, known or suspected defect of the immune system, any inactivated vaccine received within 2 weeks before vaccination with VLA1553, or any live vaccine received within 4 weeks before vaccination with VLA1553. Participants were randomised (3:1) to receive VLA1553 or placebo. The primary endpoint was the proportion of baseline negative participants with a seroprotective chikungunya virus antibody level defined as 50% plaque reduction in a micro plaque reduction neutralisation test (μPRNT) with a μPRNT50 titre of at least 150, 28 days after vaccination. The safety analysis included all individuals who received vaccination. Immunogenicity analyses were done in a subset of participants at 12 pre-selected study sites. These participants were required to have no major protocol deviations to be included in the per-protocol population for immunogenicity analyses. This trial is registered at ClinicalTrials.gov, NCT04546724.FindingsBetween Sept 17, 2020 and April 10, 2021, 6100 people were screened for eligibility. 1972 people were excluded and 4128 participants were enrolled and randomised (3093 to VLA1553 and 1035 to placebo). 358 participants in the VLA1553 group and 133 participants in the placebo group discontinued before trial end. The per-protocol population for immunogenicity analysis comprised 362 participants (266 in the VLA1553 group and 96 in the placebo group). After a single vaccination, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 263 (98·9%) of 266 participants in the VLA1553 group (95% CI 96·7–99·8; p<0·0001) 28 days post-vaccination, independent of age. VLA1553 was generally safe with an adverse event profile similar to other licensed vaccines and equally well tolerated in younger and older adults. Serious adverse events were reported in 46 (1·5%) of 3082 participants exposed to VLA1553 and eight (0·8%) of 1033 participants in the placebo arm. Only two serious adverse events were considered related to VLA1553 treatment (one mild myalgia and one syndrome of inappropriate antidiuretic hormone secretion). Both participants recovered fully.InterpretationThe strong immune response and the generation of seroprotective titres in almost all vaccinated participants suggests that VLA1553 is an excellent candidate for the prevention of disease caused by chikungunya virus.FundingValneva, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020.

Abstract licence: CC BY-NC-ND

In recent decades, there has been an increased interest in developing a vaccine for chikungunya. However, due to its unpredictable transmission, planning for a chikungunya vaccine trial is challenging. To inform decision making on the selection of sites for a vaccine efficacy trial, we developed a new framework for projecting the expected number of endpoint events at a given site. In this framework, we first accounted for population immunity using serological data collated from a systematic review and used it to estimate parameters related to the timing and size of past outbreaks, as predicted by an SIR transmission model. Then, we used that model to project the infection attack rate of a hypothetical future outbreak, in the event that one were to occur at the time of a future trial. This informed projections of how many endpoint events could be expected if a trial were to take place at that site. Our results suggest that some sites may have sufficient transmission potential and susceptibility to support future vaccine trials, in the event that an outbreak were to occur at those sites. In general, we conclude that sites that have experienced outbreaks within the past 10 years may be poorer targets for chikungunya vaccine efficacy trials in the near future. Our framework also generates projections of the numbers of endpoint events by age, which could inform study participant recruitment efforts.

Abstract licence: CC BY

Chikungunya is a neglected tropical disease of growing public health concern with outbreaks in more than 114 countries in Asia, Africa, Americas, Europe, and Oceania since 2004. There are no specific antiviral treatment options for chikungunya virus infection. This article describes the chikungunya vaccine pipeline and assesses the challenges in the path to licensure, access, and uptake of chikungunya vaccines in populations at risk. Ixchiq (VLA1533/Ixchiq - Valneva) was the first licensed chikungunya vaccine by the US Food and Drug Administration in November 2023, European Medicines Agency in May 2024, and Health Canada in June 2024. Five chikungunya vaccine candidates (BBV87 - BBIL/IVI, MV-CHIK - Themis Bioscience, ChAdOx1 Chik - University of Oxford, PXVX0317 / VRC-CHKVLP059-00-VP - Bavarian Nordic, and mRNA-1388 - Moderna) are in development. Evidence on chikungunya disease burden alongside the public health and economic impact of vaccination are critical for decision-making on chikungunya vaccine introduction in endemic and epidemic settings. Further, global and regional stakeholders need to agree on a sustainable financing mechanism for manufacturing at scale to facilitate fair access and equitable vaccine distribution to at-risk populations in different geographic settings. This could partly be facilitated through obtaining consensus on scientific and regulatory principles for initial vaccine introduction and generating evidence on chikungunya burden and disease awareness among populations at risk. Specifically, this article advocates for the formation of a global chikungunya vaccine consortium that includes regulators, policymakers, sponsors, and manufacturers to assist in overcoming the global and local challenges for chikungunya vaccine licensure, policy, financing, demand generation, and access to at-risk populations.

Abstract licence: CC BY

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the US FDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. This article explores various vaccine candidates, including live attenuated, killed, nucleic acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines have emerged as promising candidates due to their rapid response capabilities and enhanced safety profile. This review underscores the importance of the E1 and E2 proteins as immunogens, emphasizing their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates. This article discusses potential antiviral targets, the significance of E1 and E2 proteins, monoclonal antibodies, and RNA vaccines as prospective Chikungunya virus vaccine candidates.

Abstract licence: CC BY

CHIKV is a re-emerging mosquito-borne arthritogenic alphavirus associated with large outbreaks and severe joint pain, and it poses a growing global health threat. Toll-like receptors (TLRs), as key pattern recognition receptors, detect viral components and initiate antiviral immune responses. Increasing evidence highlights the role of TLR signaling in shaping CHIKV infection outcomes, though its precise contribution remains unclear. CHIKV has developed mechanisms to evade host innate immune surveillance, promoting viral replication. TLR agonists show promise as vaccine adjuvants by enhancing immune responses. In this review, we summarize current insights into TLR-mediated immunity during CHIKV infection, the virus's innate immune evasion strategies, and the potential of TLR agonists in improving vaccine efficacy.

Abstract licence: CC BY