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.
Bielinska
Anna U
AU
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
Chepurnov
Alexander A
AA
Landers
Jeffrey J
JJ
Janczak
Katarzyna W
KW
Chepurnova
Tatiana S
TS
Luker
Gary D
GD
Baker
James R
JR
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