We conducted studies with mice, rats, and monkeys which demonstrated the ability of glucan to induce either nonspecific or specific enhancement of host resistance to infectious diseases. Intravenous pretreatment of mice with glucan significantly enhanced the survival of mice challenged with either Venezuelan equine encephalomyelitis (VEE) virus or Rift Valley fever virus. Pretreatment was beneficial when initiated 3 days before challenge with VEE virus and 7 days before challenge with Rift Valley fever virus. Treatment of mice after VEE challenge did not increase their survival compared with controls. Glucan pretreatment of rats provided increased resistance to both intraperitoneal and low-dose aerosol challenges with virulent Francisella tularensis when the glucan was given intravenously, but not when it was administered intranasally. In contrast, intranasal glucan pretreatment enhanced the survival of mice when they were challenged by aerosol with Pseudomonas pseudomallei, whereas intravenous glucan pretreatment did not increase survival. mice given glucan combined with a marginally immunogenic dose of VEE vaccine were more resistant to homologous virus challenge than were mice given either Freund complete adjuvant plus vaccine or vaccine alone. Similarly, both primary and secondary VEE antibody titers in cynomolgus monkeys given glucan with VEE vaccine were significantly greater than titers in vaccine controls.

Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with anthrax toxin in Fischer 344 rats and against aerosol or intramuscular challenge with virulent anthrax spores in Hartley guinea pigs. Animals immunized with toxigenic, nonencapsulated (pXO1+, pXO2-) strains survived toxin and spore challenge and demonstrated postimmunization antibody titers to the three components of anthrax toxin (protective antigen, lethal factor, and edema factor). Immunization with two nontoxigenic, encapsulated (pXO1-, pXO2+), Pasteur vaccine strains neither provided protection nor elicited titers to any of the toxin components. Therefore, to immunize successfully against anthrax toxin or spore challenge, attenuated, live strains of B. anthracis must produce the toxin components specified by the pXO1 plasmid.

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.

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Effect of aerosol age on the infectivity of airborne Pasteurella tularensis for Macaca mulatta and man. J. Bacteriol. 91:2180-2184. 1966.-In aging aerosols of Pasteurella tularensis SCHU-S4, the respiratory infectivity for man and Macaca mulatta decreased more rapidly than the viability of the organisms. Infectivity was diminished after 120 min, and was reduced 10-fold after 180 min. These findings confirmed previous observations made in mice and guinea pigs, and also revealed that smaller losses of infectivity were detectable in the primate hosts.

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The results obtained in this study indicate that serum protease is not activated by either a rabbit or guinea pig antiovalbumin-ovalbumin system, in vitro. A precipitin reaction occurring in the presence of a serum protease precursor of three species (human, rabbit, and guinea pig) failed to activate the protease precursor. Furthermore, particulate material as preformed precipitates could not be shown to activate the protease of either human or rabbit serum or their euglobulin fractions. The material presented seems to be further evidence against the postulated role of serum protease in immunologic systems.

Mice were vaccinated intranasally (i.n.) or with small-particle aerosols (SPA; 2 ,um) or large-particle aerosols (LPA; 8 ,tm) of an attenuated, temperature-