Valneva Austria GmbH, Austria
Title: Chikungunya – A reemerged tropical disease: Development of a live- attenuated vaccine
Biography: Andrea Fritzer
Chikungunya virus (CHIKV) is a mosquito-borne virus resulting in many patients in chronic and incapacitating arthralgia affecting all gender and age groups. CHIKV was typically transmitted by Aedes aegypti mosquitos however, an adaptation enabled unusually efficient transmission by Aedes albopictus mosquitos. Thus, the virus re-emerged in 2004 and rapidly spread over Africa, Asia, the Americas and locally also in Europe since then. CHIKV is regarded as one of the most-likely re-emerged viruses to spread globally. Morbidity due to this virus is considered a serious threat to global public health raising an urgent demand for efficient prophylaxis. However, at present there is no treatment or vaccine available. Facing the unmet medical need for a prophylactic intervention, we initiated a program to develop a vaccine candidate (VLA1553) against CHIKV infections.
Valneva’s live-attenuated CHIKV vaccine candidate, VLA1553, is based on the La Reunion strain of the East Central South African genotype. The Vero cell based vaccine is characterized by a 60 amino acid deletion in the nsP3 viral replicase complex gene leading to attenuation of the virus in vivo.
The safety, immunogenicity as well as protective efficacy of the vaccine candidate was evaluated in mice and non-human primates. We demonstrate, that our vaccine candidate is highly attenuated in animal models and causes no clinical manifestations typically associated with wild-type CHIKV infections in addition to strongly reduced viremia and cytokine levels. Moreover, VLA1553 is highly immunogenic and induces a strong and long-lasting neutralizing antibody response in animal models. In addition, cross-neutralizing antibodies against a Caribbean CHIKV strain are induced. VLA1553 protects against a high dose wild-type CHIKV challenge after a single immunization and no anamnestic response was observed after challenge.
Due to its safe and immunogenic potential we entered into a blinded, randomized phase 1 first-in-human clinical study investigating the safety and immunogenicity of three dose levels administered intramuscularly in a CHIKV-naïve population as a single-shot immunization designed to elicit long-term immunological memory (NCT:NCT03382964).
Hallengärd D, Kakoulidou M, Lulla A, Kümmerer BM, Johansson DX, Mutso M, Lulla V, Fazakerley JK, Roques P, Le Grand R, Merits A, Liljeström P (2014) Novel attenuated Chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice. J Virol 88:2858-2866.
- Roques P, Ljungberg K, Kümmerer BM, Gosse L, Dereuddre-Bosquet N, Tchitchek N, Hallengärd D, Garcia-Arriaza J, Meinke A, Esteban M, Merits A, Le Grand R, Liljeström P (2017) Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus. J Clin Invest Insight 2:e83527.