Development of inactivated zika virus vaccine by irradiation
Boonrat Tassaneetrithep1, Suwimol Jetawattana2, Chintana Phawong1, Witthawat Wiriyarat3, Yada Akkhawattanangkul4, Komgrid Charngkaew5, Nusara Chomanee5, Artit Wongsa1, Thongkoon Priengprom1, Chidchanok Ritkamrop1, Puttawat Suphaprueksapong1, Pumin Sintara1.
1Center of Research Excellence in Immunoregulation, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Academic Service Unit, Thailand Institute of Nuclear Technology, Nakhon Nayok, Thailand; 3The Monitoring and Surveillance Center for Zoonotic Diseases in Wildlife and Exotic Animals, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand; 4Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand; 5Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Zika virus disease is an infectious disease caused by mosquito-borne Zika virus (ZIKV). Zika virus infection during pregnancy may cause a birth defect called microcephaly and other central nervous system anomalies. The Zika virus is found worldwide with many lineages and strains, and there is no specific therapy or effective vaccine available. The objective of this study is to develop inactivated Thai strain Zika virus vaccine by gamma irradiation for local use in Thailand. We compared the effects of gamma irradiation on the Zika virus at 25, 50, and 100 kilogray (kGy). The virus was killed at all doses and viral genomes were still preserved. Only 25 and 50 kGy did not affect the morphology and virion size, and the immunogenicity did not differ significantly from non-irradiated viruses. The dose of 25 kGy was chosen to prepare the vaccine, with alum adjuvant, to test for safety and immunogenicity in animal model, using 2 doses of subcutaneous vaccination, 2 weeks apart to Balb/c mice. It was no effect on health or death. The vaccine-induced antibodies to Zika virus were non-neutralizing, resulting in no inhibition of Zika virus infection in vitro. The vaccine induced T cell proliferation and tended to induce cytokine production in splenocytes, but it was not significant. The vaccine might elicit better cellular immune responses than humoral immune responses. Using higher amounts of Zika protein in the vaccine will probably be able to induce better immune responses. We will also try other types of radiation, including X-ray and electron beams. Further study is needed to develop a safe and effective Zika virus vaccine for Thai people, especially pregnant women, who are at risk of Zika virus infection.
