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- Title
Construction of a recombinant vaccine expressing Nipah virus glycoprotein using the replicative and highly attenuated vaccinia virus strain LC16m8.
- Authors
Watanabe, Shumpei; Yoshikawa, Tomoki; Kaku, Yoshihiro; Kurosu, Takeshi; Fukushi, Shuetsu; Sugimoto, Satoko; Nishisaka, Yuki; Fuji, Hikaru; Marsh, Glenn; Maeda, Ken; Ebihara, Hideki; Morikawa, Shigeru; Shimojima, Masayuki; Saijo, Masayuki
- Abstract
Nipah virus (NiV) is a highly pathogenic zoonotic virus that causes severe encephalitis and respiratory diseases and has a high mortality rate in humans (>40%). Epidemiological studies on various fruit bat species, which are natural reservoirs of the virus, have shown that NiV is widely distributed throughout Southeast Asia. Therefore, there is an urgent need to develop effective NiV vaccines. In this study, we generated recombinant vaccinia viruses expressing the NiV glycoprotein (G) or fusion (F) protein using the LC16m8 strain, and examined their antigenicity and ability to induce immunity. Neutralizing antibodies against NiV were successfully induced in hamsters inoculated with LC16m8 expressing NiV G or F, and the antibody titers were higher than those induced by other vaccinia virus vectors previously reported to prevent lethal NiV infection. These findings indicate that the LC16m8-based vaccine format has superior features as a proliferative vaccine compared with other poxvirus-based vaccines. Moreover, the data collected over the course of antibody elevation during three rounds of vaccination in hamsters provide an important basis for the clinical use of vaccinia virus-based vaccines against NiV disease. Trial Registration: NCT05398796. Author summary: The Nipah virus (NiV) is an emerging paramyxovirus that is widely observed in Southeast Asia and causes fatal respiratory and neurological diseases in humans and animals. The World Health Organization considers NiV diseases priority infectious disease for which an effective vaccine should be developed. LC16m8 is a highly attenuated strain of the vaccinia virus, and more than 100,000 people have been vaccinated against it in Japan without severe side effects. Compared to other attenuated vaccinia virus vaccines, LC16m8 has a relatively high or modest proliferative potential in mammalian hosts, resulting in efficient induction of immune responses in humans. In the present study, we successfully generated recombinant LC16m8 expressing the surface glycoprotein of NiV and confirmed that these vaccine candidates could efficiently induce neutralizing antibodies against NiV in hamsters.
- Subjects
SOUTHEAST Asia; VACCINIA; NIPAH virus; WORLD Health Organization; ANIMAL diseases; VACCINE effectiveness; VIRAL vaccines; Q fever; MELIOIDOSIS
- Publication
PLoS Neglected Tropical Diseases, 2023, Vol 17, Issue 12, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0011851