Primary and Secondary Antibody Responses of Chickens to Pasteurella Tularensis

Nutter, John E.

doi:10.21236/ad0808292

Cited by 1 publication

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“…There are only two reports in the literature, from studies conducted back in the 1960s, describing immune responses to F. tularensis LVS given to rabbits by different routes [18; 20]. One of them focused on cellular interactions between F. tularensis and macrophages [18] and the other one on procedures to enhance antibody production, such as combination of LVS with Freund adjuvant and use of accelerated immunization schedules, in proof of principle experiments [20]. These studies did not address vaccine safety and tolerability nor describe the pathology or microbiology related to LVS inoculations [17].…”

Section: Discussionmentioning

confidence: 99%

An improved Francisella tularensis live vaccine strain (LVS) is well tolerated and highly immunogenic when administered to rabbits in escalating doses using various immunization routes

Pasetti¹,

Cuberos²,

Horn³

et al. 2008

Vaccine

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Tularemia is a severe disease for which there is no licensed vaccine. An attenuated F. tularensis live vaccine strain (LVS) was protective when administered to humans but safety concerns precluded its licensure and use in large scale immunization. An improved F. tularensis LVS preparation was produced under current Good Manufacturing Practice (cGMP) guidelines for evaluation in clinical trials. Preclinical safety, tolerability and immunogenicity were investigated in rabbits that received LVS in escalating doses (1x10 5 to 1x10 9 CFU) by the intradermal, subcutaneous or percutaneous (scarification) route. This improved LVS formulation was well tolerated at all doses; no death or adverse clinical signs were observed and necropsies showed no signs of pathology. No live organisms were detected in liver or spleen. Transient local reactogenicity was observed after scarification injection. Erythema and edema developed after intradermal injection in the highest dose cohorts. High levels of F. tularensis-specific IgM, IgG and IgA developed early after immunization, in a dose-dependent fashion. Scarification elicited higher levels of IgA. Antibodies elicited by LVS also recognized F. tularensis Schu-S4 antigens and there was a significant correlation between antibody titers measured against both LVS and Schu-S4. The ELISA titers also correlated closely with those measured by microagglutination. This is the first report describing comprehensive toxicological and immunological studies of F. tularensis LVS in rabbits. This animal model, which closely resembles human disease, proved adequate to assess safety and immunogenicity of F. tularensis vaccine candidates. This new LVS vaccine preparation is being evaluated in human clinical studies.

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Section: Discussionmentioning

confidence: 99%