title: A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.
abstract: Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels ( approximately 2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (approximately 10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.
authors.affiliation: Modern Virology Research Center and AIDS Center, State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, People's Republic of China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Fang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ke
authors.initials: K
authors.lastname: Zhuang
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Po
authors.initials: P
authors.lastname: Tian
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors; D023281:Genomics; D007107:Immune System; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism; D012900:Smallpox Vaccine / Q000737:chemistry; D014611:Vaccination; D014612:Vaccines; D014613:Vaccines, Attenuated / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014612:Vaccines; D014613:Vaccines, Attenuated