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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.
AuthorsXiaoxing Huang, Bin Lu, Wenbo Yu, Qing Fang, Li Liu, Ke Zhuang, Tingting Shen, Haibo Wang, Po Tian, Linqi Zhang, Zhiwei Chen
JournalPloS one (PLoS One) Vol. 4 Issue 1 Pg. e4180 ( 2009) ISSN: 1932-6203 [Electronic] United States
PMID19159014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Viral
  • Smallpox Vaccine
  • Vaccines
  • Vaccines, Attenuated
Topics
  • Animals
  • Antibodies, Viral (chemistry)
  • Female
  • Genetic Vectors
  • Genomics
  • Immune System
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • SARS Virus (metabolism)
  • Smallpox Vaccine (chemistry)
  • Vaccination
  • Vaccines
  • Vaccines, Attenuated (genetics)
  • Vaccinia virus (genetics)

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