原创力文档side-by-side comparison of gene-based smallpox vaccine with mva in nonhuman primates基于基因的天花疫苗的对比与mva非人灵长类动物.pdfVIP
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side-by-side comparison of gene-based smallpox vaccine with mva in nonhuman primates基于基因的天花疫苗的对比与mva非人灵长类动物
Side-by-Side Comparison of Gene-Based Smallpox
Vaccine with MVA in Nonhuman Primates
1 1 2 3 4 3
Joseph W. Golden , Matthew Josleyn , Eric M. Mucker , Chien-Fu Hung , Peter T. Loudon , T. C. Wu ,
Jay W. Hooper1*
1 Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of
America, 2 Department of Viral Therapeutics, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States
of America, 3 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America, 4 Pfizer, Sandwich Laboratories, Sandwich,
Kent, United Kingdom
Abstract
Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with
serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the
most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed
4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates
from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia
coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly
increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a
monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice wit
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