Aerogenic Immunization of the Monkey and Guinea Pig with Live Tularemia Vaccine

Oral immunization of mice with the live vaccine strain (LVS) of Francisella tularensis protects mice against respiratory challenge with virulent type A F. tularensis

“…On the other hand, it has been shown previously in humans, guinea pigs, and monkeys [10,11], and more recently in mice [14,15] that aerosol or intranasal administration of LVS enhances protection against subsequent respiratory challenge with virulent type A F. tularensis, suggesting that the induction of local mucosal immune responses may be important for the control of tularemia initiated via the respiratory route. However, LVS retains residual virulence when administered as an aerosol and can cause overt tularemia in experimental animals and humans [8,11,15]. Therefore, the present study evaluated the potential of oral LVS immunization for its ability to elicit a protective immune response against systemic and respiratory tularemia using murine models of the disease.…”

“…Limited epidemiological evidence and experimental studies in human volunteers and animal models indicate that systemic vaccination with LVS provides solid protection against subsequent massive systemic challenge with highly virulent type A F. tularensis, and, to a lesser extent, against the airborne pathogen [4,5,8,11,[13][14][15][24][25][26]. This could be a concern because typhoidal tularemia, the deadliest form of the disease with a mortality rate of >30% if untreated, is thought to be initiated by inhalation of the pathogen and the respiratory route is considered a likely portal in the event of a bioterrorist attack [6].…”

“…This could be a concern because typhoidal tularemia, the deadliest form of the disease with a mortality rate of >30% if untreated, is thought to be initiated by inhalation of the pathogen and the respiratory route is considered a likely portal in the event of a bioterrorist attack [6]. On the other hand, it has been shown previously in humans, guinea pigs, and monkeys [10,11], and more recently in mice [14,15] that aerosol or intranasal administration of LVS enhances protection against subsequent respiratory challenge with virulent type A F. tularensis, suggesting that the induction of local mucosal immune responses may be important for the control of tularemia initiated via the respiratory route. However, LVS retains residual virulence when administered as an aerosol and can cause overt tularemia in experimental animals and humans [8,11,15].…”

“…This vaccine, when given by scarification, protects well against subsequent exposure to large dose systemic and small dose aerosol challenge with type A F. tularensis, but appears to be less protective against large dose aerosol challenge [4,5,8,9]. These findings were mimicked in animal models of tularemia using monkeys, guinea pigs and mice [10][11][12][13][14]. Thus, continued efforts to explore improved tularemia vaccine formulations and/or alternative immunization strategies for effective control of respiratory infection with the highly virulent type A F. tularensis are warranted.…”

“…Thus, continued efforts to explore improved tularemia vaccine formulations and/or alternative immunization strategies for effective control of respiratory infection with the highly virulent type A F. tularensis are warranted. In this regard, it has been shown that, compared to systemic immunization, immunization of mice, monkeys, guinea pigs, and humans with LVS by aerosol or intranasal inoculation afforded better protection against subsequent respiratory challenge with type A F. tularensis [8,11,14,15]. However, LVS is much more virulent for humans and experimental animals when administered by the respiratory route than the dermal route [8,11,16].…”