Twenty‐four specific pathogen‐free beagles were randomly allocated into four groups (three vaccinated groups and one control group) and inoculated at nine and 12 weeks of age with one of three commercial inactivated Leptospira vaccines: A (Vanguard 7; Pfizer Santé Animale), B (Dohyvac 7L; Fort Dodge), and C (Nobivac DHPPi + Lepto; Intervet Intemational); the control group received Nobivac DHPPi (Intervet International). Seven weeks after the second vaccination all the dogs were challenged with Leptospira interrogans serogroup canicola. All the vaccinated dogs developed a mild serological response (microscopic agglutination titres) after the booster vaccination. A significant serological response after the challenge was observed, particularly in the controls. The challenge induced fever and clinical disorders in the control group, whereas in the vaccinated groups the clinical signs were mild. Blood cultures became positive in all control dogs, and in one of six dogs vaccinated with vaccine A and two of four dogs vaccinated with vaccine B; none of the six dogs vaccinated with vaccine C was leptospiraemic at any stage of the experiment. Urine cultures were positive in all the control dogs two weeks after the challenge. One of six dogs vaccinated with vaccine A and two of four dogs vaccinated with vaccine B shed bacteria in their urine after the challenge, but none of the dogs vaccinated with vaccine C shed bacteria in their urine at any time during the experiment.
Idiotypic specificity can also serve as a V-region genetic marker. This is the case when a shared idiotype is present on some of the antibodies made in response to an antigen in nearly all mice of one or more inbred strains but not in other strains.Idiotypic specificities have been localized to V regions (5, 6), and a number of genetic studies with inbred mice have demonstrated linkage between genes governing idiotype and CH region allotypes (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Genetic recombination between genes governing idiotype and allotype has been reported (14-17). In the system used in the present studies, an idiotype that appears in antibodies to the p-azophenylarsonate hapten (anti-Ar antibodies) of all A/J mice (20) is also expressed by the AL/N strain (7), which has a CH-allotype similar to but distinct from that of strain A/J (21). The C.AL-20 strain, which possesses the CH region allotype of AL/N on the genetic background of the idiotype-negative (Id-) BALB/c strain, is idiotype-positive (Id+), demonstrating the linkage of idiotype with allotype (7).Results that suggest linkage of idiotype solely with CH region allotype are paradoxical, because the light (L) chain is known to be required for expression of all such idiotypes tested to date (including the anti-Ar idiotype of A/J mice) (e.g., refs. 22 and 23), and the genes governing H and L chain expression are thought to be unlinked in man (24), rabbit (25,26), and mouse (see below). A possible explanation for these results is that the various inbred strains employed in these studies possess similar or identical VL region repertoires while differing with respect to their VH region repertoires.Data consistent with this explanation were provided by the observation that L chains from normal serum IgG of most inbred strains of mice gave identical patterns of cysteine-containing peptides when analyzed by tryptic peptide mapping (27). However, such peptide maps of L chains obtained from four inbred strains (AKR/J, C58/J, PL/J, and RF/J) were distinct from those of all other mice tested, and amino acid sequence analysis of the cysteine-containing peptides unique to L chains from these strains indicated that they were derived from the V region of the K L chain (VK).
Inoculation of rabbit anti-idiotypic (anti-id) antibodies suppresses the subsequent appearance of a cross-reactive idiotype (CRI) associated with the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. Such suppressed mice produce normal concentrations of anti-Ar antibodies which lack the CRI, but against which anti-id antisera can be prepared. The anti-Ar antibodies of an individual, suppressed mouse do not in general share idiotype with anti-Ar antibodies of other A/J mice, either suppressed or nonsuppressed. The present experiments were undertaken to quantitate several "private idiotypes" in a large number of hyperimmunized A/J mice. Anti-Ar antibodies of three mice, suppressed for the CRI, were labeled with 125I and subjected to isoelectric focusing. Four single peaks, that were over 90% reactive with autologous antiid, were randomly selected for use as ligands in a radioimmunoassay, and ascitic fluids containing anti-Ar antibodies from 181 A/J mice were tested as inhibitors. Two of the four idiotypes could not be detected in any mouse other than the donor. The concentration of the idiotype was less than 1 part in 1,250 to less than 1 part in 25,000 of the anti-Ar antibody population; these are minimum values. A third idiotype was detected in 3 of the 181 mice, but at very low concentrations. The fourth idiotype was present in 28% of the mice, again at a low concentration. The data support the existence of a very large repertoire of anti-Ar antibodies in the A/J strain and are consistent with a process of random somatic mutation for generating diversity in hypervariable regions. It is proposed that the cross-reactive idiotype may be controlled by a germ line gene or a gene related to a germ line gene through a small number of somatic mutations; and that the idiotypes that were not detectable in other mice were the products of genes that had undergone extensive mutations, with a low probability of recurrence in other mice.
A novel intranasal vaccine against disease caused by Bordetella bronchiseptica in cats was tested in a series of three experiments. In the first experiment a vaccinated group and an unvaccinated control group of kittens were challenged by the aerosol route with virulent B bronchiseptica three weeks after they had been vaccinated. The control kittens developed upper respiratory tract signs typical of feline B bronchiseptica infection, including rhinitis, a serous ocular and nasal discharge, fever, sneezing and coughing. The mean (sd) clinical score for the cats in the unvaccinated control group was 19.5 (5.4) compared with 1.53 (1.9) for the vaccinated group. In the second experiment vaccinated kittens were challenged with virulent B bronchiseptica 72 hours after they were vaccinated. Their mean clinical score was 2.76 (2.62) compared with 13.4 (3.33) for the control group. In the final experiment, vaccinated and unvaccinated control cats were challenged after six or 12 months. After six months the mean clinical scores were 13.9 (4.7) for the control group, compared with 1.33 (1.56) for the vaccinated group, and after 12 months the scores were 9.92 (5.79) for the control group compared with 0.92 (0.89) for the vaccinated group.
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