Host range restricted, non-replicating vaccinia virus vectors as vaccine candidates.
Three model systems were used to demonstrate the immunogenicity of highly attenuated and replication-defective recombinant MVA. (1) Intramuscular inoculation of MVA-IN-Fha/np induced humoral and cell-mediated immune responses in mice and protectively immunized them against a lethal respiratory challenge with influenza virus. Intranasal vaccination was also protective, although higher doses were needed. (2) In rhesus macaques, an immunization scheme involving intramuscular injections of MVA-SIVenv/gag/pol greatly reduced the severity of disease caused by an SIV challenge. (3) In a murine cancer model, immunization with MVA-beta gal prevented the establishment of tumor metastases and even prolonged life in animals with established tumors. These results, together with previous data on the safety of MVA in humans, suggest the potential usefulness of recombinant MVA for prophylactic vaccination and therapeutic treatment of infectious diseases and cancer.
Moss
B
B
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Carroll
M W
MW
Wyatt
L S
LS
Bennink
J R
JR
Hirsch
V M
VM
Goldstein
S
S
Elkins
W R
WR
Fuerst
T R
TR
Lifson
J D
JD
Piatak
M
M
Restifo
N P
NP
Overwijk
W
W
Chamberlain
R
R
Rosenberg
S A
SA
Sutter
G
G
D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control; D005822:Genetic Vectors; D006801:Humans; D007252:Influenza Vaccines; D009374:Neoplasms, Experimental / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus; D014162:Transfection; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000502:physiology; D014765:Viral Vaccines; D014779:Virus Replication
D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines