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The last two years in scientific news
Scientific result | Highlight | Health ＆ life sciences | Vaccine | Infectious diseases | Chikungunya
In a study published in JCI Insight, researchers from IDMIT have demonstrated the vaccinal effectiveness of serum transfers from volunteers vaccinated against the chikungunya virus to an animal model. The team also quantified a neutralization test titer able to act as a surrogate of protection. This work is an important step toward vaccine marketing approval, as the nature of chikungunya epidemics hampers the deployment of conventional efficacy trials.
The arbovirus chikungunya (CHIKV) was first identified in Tanzania in 1952. Infection by it occurs via bites from Aedes genus mosquitos and causes most notably debilitating joint pain in the patient. Chikungunya epidemics were noted in tropical zones of Asia and Africa in the 1970s and 1980s and thereafter on Réunion Island in 2005. In 2010, the disease became a more global issue, with new outbreaks occurring in Asia, India, Africa and finally South America, due most notably to the invasive arrival of tiger mosquitos (Aedes albopictus), one of the main vector species for CHIKV. Now considered endemic in those regions, chikungunya causes recurrent epidemics involving millions of people.
In 2005, during the epidemic on Réunion Island, a team from IDMIT (CEA-Jacob) developed a non-human primate (NHP) model of CHIKV infection to characterize the pathophysiology of the infection (Labadie et al., 2010). That model enabled the demonstration of viral persistence and the potential role of that persistence in lingering arthralgia and other symptoms experienced by many patients.
After that initial work and with the first autochthonous infections in Italy resulting from the tiger mosquito's arrival in southern Europe, an H2020 (ICRES) program brought together French (IDMIT and UMR-S 1184 (Inserm/ UPSaclay/CEA Fontenay-aux-Roses)), Swedish, English and German teams to evaluate a range of vaccine candidates (subunit, inactivated virus, attenuated virus, etc.) in mouse models (Hallengärd et al., 2014) and in the NHP model developed by IDMIT (Roques et al., 2017). The resulting studies first financed by Europe then by the company Valneva led to the identification of a very promising and easily-deployed attenuated-virus vaccine candidate, called VLA1553 and developed at the Karolinska Institutet in Sweden. Because of the relatively small population affected by CHIKV and the unpredictably of epidemics, Valneva benefited from a European program (CEPI) in 2010 to carry out phase I trials (Wressningg et al., 2020).
For their recent work published in JCI Insight, the IDMIT researchers performed a passive transfer of sera from human volunteers vaccinated with VLA1553 to the non-human primates, then exposed these latter to wild-type CHIKV. The researchers found that the vaccinated human sera protected the NHPs from CHIKV viremia, fever and other clinical symptoms associated with the pathogen, and furthermore from viral persistence in the tissues. Building upon those first results, the team also quantified a neutralization test titer able to act as a surrogate of protection and further verified its pertinence with an analysis of seroepidemiology samples.
This most recent study by the IDMIT researchers and especially the surrogate of protection they established carry great importance for marketing approval of VLA1553, as this latter cannot be tested in a conventional efficacy trial due to the unpredictable, rapid and explosive nature of CHIKV outbreaks.
Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera | JCI Insight
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.