A novel, killed-virus nasal vaccinia virus vaccine.
Live-virus vaccines for smallpox are effective but have risks that are no longer acceptable for routine use in populations at minimal risk of infection. We have developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for at least 60 min causes the complete disruption and inactivation of VV. Simple mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE vaccine produced protection against lethal infection equal to vaccination by scarification, with 100% survival after challenge with 77 times the 50% lethal dose of live VV. However, animals protected with VV/NE immunization did after virus challenge have clinical symptoms more extensive than animals vaccinated by scarification. VV/NE-based vaccines are highly immunogenic and induce protective mucosal and systemic immunity without the need for an inflammatory adjuvant or infection with live virus.
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
Anna U
AU
Bielinska
Alexander A
AA
Chepurnov
Jeffrey J
JJ
Landers
Katarzyna W
KW
Janczak
Tatiana S
TS
Chepurnova
Gary D
GD
Luker
James R
JR
Baker
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012899:Smallpox / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D038301:Virus Inactivation
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012900:Smallpox Vaccine; D015164:Vaccines, Inactivated; D007371:Interferon-gamma