Respiratory tularemia: comparison of selected routes of vaccination in Fischer 344 rats

Abstract

Fischer 344 rats were given the attenuated live vaccine strain of Francisella tularensis by small-particle aerosol, intranasal instillation, or intraperitoneal, intramuscular, or subcutaneous injection. All of the vaccinated rats developed subclinical infection by 3 days after exposure, which cleared by day 28. Temporal patterns and concentrations of the live vaccine strain organism within the hosts were dependent on the route of vaccination. Pathological alterations were limited to minimal lung lesions in aerosol-vaccinated rats and mild splenitis in intraperitoneally vaccinated rats. Agglutinins to live vaccine strain were detected in the serum of each vaccinated animal and in the bronchoalveolar wash fluids of 66% of the aerosol-vaccinated rats. Agglutinin activity of the vaccinated rats was associated predominantly with the immunoglobulin M class. Regardless of the route of vaccine administration, all vaccinated rats survived an aerosol challenge of 5.3 log10 cells of virulent F. tularensis, whereas all nonvaccinated rats died. Systemic infection did not occur in the vaccinated rats. Pulmonary infection was not prevented in the vaccinated rats after aerosol challenge, but proliferation of the virulent F. tularensis organisms in the lungs was significantly lower (analysis of variance, P less or equal to 0.01) than that which occurred in the control animals. These studies demonstrate the utility of the inbred Fischer 344 rat as a model host for further investigations of F. tularensis infection and its associated immune response.

Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis

“…is 1 CFU in mice, 1 CFU in guinea pigs, 1 CFU in rabbits, and >10 8 CFU (s.c.) in White rats; the LD 50 of SCHU S4 by the respiratory route is 1-3 CFU in mice (i.n. ), 1 CFU in cynomolgus macaques (aerosol), and >5 × 10 2 CFU in Fisher rats (intratreacheal); in humans, as few as 10–50 CFU SCHU S4 can cause clinical tularemia (Eigelsbach et al, 1951 ; McCrumb, 1961 ; Saslaw et al, 1961a , b ; Schricker et al, 1972 ; Kostiala et al, 1975 ; Jemski, 1981 ; Conlan et al, 2003 ; Barker and Klose, 2007 ; Lyons and Wu, 2007 ; Raymond and Conlan, 2009 ; Wu et al, 2009 ; Ray et al, 2010 ; Chu et al, 2014 ; Kingry and Petersen, 2014 ; Hutt et al, 2017 ; Nguyen et al, 2017 ). Mice, rats, guinea pigs, and primates also differ in the degree of vaccine-induced protective immunity against virulent SCHU S4 challenge.…”

“…In addition to the macrophage, F. tularensis can infect alveolar type II epithelial cells, neutrophils, dendritic cells, and others (Metzger et al, 2007 ). Studies on the pathogenesis of experimental tularemia were mostly conducted in mice and to a lesser extent in Fisher rats and non-human primates (Jemski, 1981 ; Lyons and Wu, 2007 ; Hutt et al, 2017 ). Upon i.d.…”

Comparison of virulence of Francisella tularensis ssp. holarctica genotypes B.12 and B.FTNF002-00

“…The susceptibility of Fischer 344 rats to tularemia was described in previous examinations [ 17 , 19 , 20 ]. Experimental infection of Fischer 344 rats with intra-peritoneal inoculation of 10 1 CFU of a F. tularensis ssp.…”

“…Fischer 344 rats reflected best the human susceptibility to tularemia and showed higher resistance to the pathogen compared to other laboratory animals (e.g. mice) [ 17 – 20 ]. Difference in susceptibility of Fischer 344 rats to F. tularensis ssp.…”

Protection induced by a Francisella tularensis subunit vaccine delivered by glucan particles

“…tularensis vaccine efficacy testing as it is more resistant to tularemia than the highly susceptible mouse model and overall the pathogenesis of respiratory tularemia in the rat model appears to replicate tularemia in humans [ 66 ]. Killed whole cell formulations were able to induce protective immune responses in rats against systemic challenge [ 67 ] and LVS immunisation was protective against aerosol challenge [ 68 ]. The efficacy of the GP vaccines in inducing protective immune responses was therefore evaluated in the Fischer 344 rat.…”