Risk assessment of the ZKBS for a recombinant Chikungunya virus

In which Chikungunya virus (CHIKV) It is a member of the Togaviridae family. The enveloped virus has a linear, single-stranded RNA genome of positive polarity. CHIKV is transmitted by mosquitoes of the genus Aedes; natural hosts include humans, monkeys, rodents, and birds. Symptoms of CHIKV infection in humans include sudden onset of fever, rash, and joint pain. In rare cases, CHIVK infection can be fatal, especially in newborns and people with pre-existing conditions (fatality rate 0.1%). CHIKV is included in the ZKBS list of risk-assessed donor and recipient organisms for genetic engineering work. Risk group 3 assigned.

In the recombinant CHIKV Δ5nsP3 it is a attenuated virus based on an infectious clone of the CHIKV La Réunion strain. To produce CHIKV Δ5nsP3, the gene coding for the Non-structural protein 3 (nsP3) was introduced. This deletion reduces the replication capacity of CHIKV, as nsP3 plays an important role in replication and formation of virus particles. CHIKV Δ5nsP3 is currently under development as Vaccine candidate. The genetic stability The attenuation of CHIKV Δ5nsP3 is high, as has already been demonstrated by two in vitro studies. The virus showed no alterations in its genome even after 15 to 20 passages on Vero cells. In vivo, genetic stability was investigated using serum samples from participants in a Phase I study who had been administered CHIKV Δ5nsP3. Here, too, no noticeable alterations were found in the CHIVK Δ5nsP3 genome. The attenuation of CHIKV Δ5nsP3 was investigated in C57BL/6 mice, cynomolgus monkeys, and rabbits. The animals subsequently had a viral titer reduced by several logs compared to infection with the wild-type virus and showed no symptoms of disease. CHIKV Δ5nsP3 induced a strong, long-lasting, and protective effect in the animals. antibody response after a single vaccination. CHIKV Δ5nsP3 l has now been shown to be generally safe in several clinical studies. CHIKV Δ5nsP3 has therefore already been classified in risk group 1 in both Austria and Brazil. According to Section 5 Paragraph 1 GenTSV in conjunction with the criteria in Annex 1 GenTSV, the ZKBS classifies the CHIKV Δ5nsP3 of risk group 1 In contrast to the wild type, the recombinant virus is highly attenuated due to a deletion in the nsP3 gene and exhibits high genetic stability. In several studies, CHIKV Δ5nsP3 has also proven to be safe and well-tolerated.

The complete ZKBS recommendation can be found at File number 45110.2123 can be retrieved.