Trypanosoma brucei: immunogenicity of the variant surface coat glycoprotein of virulent and avirulent subspecies

Comparative analyses were made to define the immunogenic role in mice of the variant surface coat glycoprotein (VSG) of African trypanosomes. Less than 10 micrograms of the glycoprotein fixed to trypanosomes or covalently linked to sheep erythrocytes were 100 times more immunogenic than soluble VSG. Therefore, although VSG is present on the parasites and in the blood of infected hosts, the cell-bound form most likely elicits immunity. Intravenous administration of soluble or cell-bound VSG was a better route of immunization than the subcutaneous route. Therefore, although parasites grow at the site of infection, in tissue spaces, and in the blood, control of blood parasitemia is best developed if the antigen is introduced to the vascular bed. Full protection against homologous challenge occurred by 4 days and was maintained through 30 days. Trypanosome-agglutinating antibody titers could be measured at 3 days, peaked at 5 days, and remained high through 14 days after immunization. Therefore, mice immunized with an optimal dosage of VSG, 2 days before challenge, should have had ample time to elicit a protective response. Most of these mice, however, developed patent infections, and one-third died during the first peak of parasitemia at about the same time as untreated control mice. This indicates that active infection inhibits the early phases of induction of immunity. Mice, suboptimally immunized against and challenged with an avirulent isolate of Trypanosoma brucei gambiense, survived at higher rates than mice immunized and challenged with a virulent clone of T. b. rhodesiense. Cell-fixed and soluble VSG from both parasites elicited similar agglutinating-antibody titers, indicating that the two trypanosomes were equally antigenic. Results from neutralization tests, however, revealed that, per unit of immune mouse serum, 400 times more T. b. gambiense became noninfective than T. b. rhodesiense. Apparently, virulence is related to relative sensitivity of the trypanosomes to immunological assault.     

Strain-Specific Protective Effect of the Immunity Induced by Live Malarial Sporozoites under Chloroquine Cover

The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2–4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2–5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites’ circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the parasite stage at which the strain-specific protective immunity is directed, it is possible that the target of this immunity could be either the pre-erythrocytic stage, or the blood-stage, or both.     

食蟹猴疟原虫感染恒河猴的长期观察

本项研究证明,食蟹猴疟原虫感染恒河猴后出现的红细胞内期是一个长期的寄生过程,不论血传或子孢子感染,于原虫密度高峰后,均有较长期的低原虫密度阶段。恒河猴均可耐受食蟹猴疟原虫高密度的感染。     

Comparative infectivity of knobless and knobby clones of Plasmodium falciparum in splenectomized and intact Aotus trivirgatus monkeys

In two experiments, two knobless (K-) and two knob-producing (K+) clone-cultures of Plasmodium falciparum, FCR-3/Gambia strain, were injected into four Aotus trivirgatus monkeys. The parasitemia in the K(-)-infected splenectomized (S-) monkey rose to a peak of 2.1% on the 16th day, while it reached only 0.7% at the same time in the K+ infected S- animal. Passage from these animals (karyotype VI) into two intact (S+), naive monkeys of karyotype III resulted in very light infections somewhat higher with K+ than with K-. This experiment was repeated with two different clones in two other S- monkeys of karyotype III. Again, the parasitemia of the K+ infected monkey was appreciably below that of the K- monkey. Transfer of parasites into S+ animals of karyotype II resulted in very light infection and, as before, the K+ did somewhat better. About 2 months after its initial infection, the K(+)-infected S- animal from the second experiment came down with a recurrent malaria infection. Electron-microscopic observations on blood from this monkey revealed that the previously K+ parasites had become knobless (K-). Transfer of this material into an S+, naive monkey, again, gave a barely detectable infection. After splenectomy a recrudescence occurred. The results strongly indicate that K- clones of P. falciparum are more infectious to S- Aotus monkeys than K+ clones, whereas in S+ monkeys the situation is reversed.     

Trypanosoma rhodesiense: protection in mice by inoculations of homologous parasite products

Mice were immunized against Trypanosoma rhodesiense (Wellcome strain) with whole lyophilized trypanosomes, with antigens produced by disrupting lyophilized trypanosomes under pressure, and with excretions and secretions of the living parasites. The survival rate in groups of 40 mice inoculated with disrupted trypansomes and challenged with the homologous strain was 48% with a soluble fraction, and 70% with a particulate fraction of the parasites. There was 95% survival after challenge in a group immunized with lyophilized trypanosomes; none of the controls survived. Results were essentially the same whether or not an aluminum hydroxide adjuvant was used. In subsequent experiments, complete protection was obtained with either crude excretion-secretion (ES) antigens or the particulate fraction of the ES antigen, while 40% of the mice survived challenge after inoculations of ES supernatant fluid. Mice immunized with crude ES antigen failed to survive challenge with a heterologous strain, although their mean survival time was prolonged several days beyond that of the controls.     

Resistance of mice immunized with irradiated and lyophilized stages of Trypanosoma cruzi to infections with metacyclics

Okanla E. O., Stumpf J. L. &; Dusanic D. G. 1982. Resistance of mice immunized with irradiated and lyophilized stages of Trypanosoma cruzi to infections with metacyclics. International Journal for Parasitology12: 251–256. BALB/c mice were immunized with either irradiated or lyophilized metacyclic, epimastigote or bloodstream forms of Trypanosoma cruzi in three weekly injections of 1 × 10⁸ trypanosomes/injection. The lyophilized trypanosomes were emulsified in equal quantities of Freund's complete adjuvant. Two weeks following the final immunization, the mice were challenged subcutaneously with metacyclics obtained from either culture or the vector Triatoma infestans. The mice challenged with metacyclics from culture included groups of mice immunized with each of the three stages, while those challenged with metacyclics from the T. infestans included mice immunized with the epimastigotes or metacyclics. Mice immunized with the irradiated epimastigotes, metacyclics and blood-stream form trypomastigote challenged with metacyclics from culture exhibited reduced parasitemias compared to mice of the control groups. Parasitemias were lowest in those mice immunized with irradiated metacyclics. The parasitemias terminated in the immunized mice before those of the control animals. No protection was detected in the mice inoculated with lyophilized trypanosomes and challenged with culture metacyclics. Groups of mice injected with either irradiated or lyophilized epimastigotes or metacyclics and challenged with metacyclics from T. infestans exhibited resistance both by reduction of the parasitemias and the duration of the parasitemias when compared to the infected control animals. This study demonstrated the comparative effectiveness in mice of irradiated and lyophilized vaccines produced from either metacyclics, epimastigotes or bloodstream forms when challenged with metacyclics obtained from culture and the vector.     

Plasmodium berghei: biological variation in immune serum-treated mice.

Antiserum was obtained from mice which had been immunized with irradiated Plasmodium berghei parasitized erythrocytes and which survived subsequent challenge. This antiserum suppressed P. berghei infections in mice; parasitemia and mortality were delayed 7–8 days as compared to those of control animals. Parasites surviving in antiserum-treated animals were isolated by inoculation of blood into normal recipients. When antiserum was tested against this derived parasite population, there was no observable effect on parasitemia or mortality. The derived parasites also exhibited a decreased virulence for mice. This work confirms the previous observation that antiserum treatment can result in a biologically variant population of P. berghei.     

Antibody Responses to a Novel Plasmodium falciparum Merozoite Surface Protein Vaccine Correlate with Protection against Experimental Malaria Infection in Aotus Monkeys

The Block 2 region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum has been identified as a target of protective immunity by a combination of seroepidemiology and parasite population genetics. Immunogenicity studies in small animals and Aotus monkeys were used to determine the efficacy of recombinant antigens derived from this region of MSP-1 as a potential vaccine antigen. Aotus lemurinus griseimembra monkeys were immunized three times with a recombinant antigen derived from the Block 2 region of MSP-1 of the monkey-adapted challenge strain, FVO of Plasmodium falciparum, using an adjuvant suitable for use in humans. Immunofluorescent antibody assays (IFA) against erythrocytes infected with P. falciparum using sera from the immunized monkeys showed that the MSP-1 Block 2 antigen induced significant antibody responses to whole malaria parasites. MSP-1 Block 2 antigen-specific enzyme-linked immunosorbent assays (ELISA) showed no significant differences in antibody titers between immunized animals. Immunized animals were challenged with the virulent P. falciparum FVO isolate and monitored for 21 days. Two out of four immunized animals were able to control their parasitaemia during the follow-up period, whereas two out of two controls developed fulminating parasitemia. Parasite-specific serum antibody titers measured by IFA were four-fold higher in protected animals than in unprotected animals. In addition, peptide-based epitope mapping of serum antibodies from immunized Aotus showed distinct differences in epitope specificities between protected and unprotected animals.     

Immunogenicity and protective efficacy of three DNA vaccines encoding pre-erythrocytic- and erythrocytic-stage antigens of Plasmodium cynomolgi in rhesus monkeys

Although several malaria vaccine candidate antigens have been identified, the most suitable methods for their delivery are still being investigated. In this regard, direct immunization with DNA encoding these vaccine target antigens is an attractive alternative. Here, we have investigated the immune responses to DNA immunization with three major vaccine target antigens: the apical membrane antigen-1 and the 19-kDa C-terminal fragment of merozoite surface protein-1 from the erythrocytic stage, and the thrombospondin-related adhesive protein from the pre-erythrocytic stage of Plasmodium cynomolgi in rhesus monkeys. Antigen-specific antibodies were developed in all the immunized monkeys and peripheral blood mononuclear cells from all immunized monkeys proliferated to different extents upon in vitro stimulation with the corresponding recombinant proteins. The immunized monkeys were challenged with P. cynomolgi sporozoites. All of the immunized animals developed infection but although there was no significant difference between the control and vaccinated animals in terms of pre-patent period, total duration of patency and primary peak parasitemia, the vaccinated animals had significantly lower secondary peak parasitemia than the control animals.     

Plasmodium fragile: Inhibition of cultures by serum from Rhesus monkeys immunized with homologous parasites

Rhesus monkeys, Macaco mulatto, that had previously been immunized with the Nilgiri strain of Plasmodium fragile grown in culture, together with control monkeys with and without inoculation of Freund's adjuvant, were challenged with cultured parasites. After treatment with chloroquine, the monkeys were rechallenged. Serum specimens from three immunized monkeys caused a specific, dose-dependent inhibition of parasite growth in culture. Fifty percent inhibition of in vitro growth was obtained using 5% immune serum combined with 10% normal rhesus serum. The specific inhibitory component of immune serum was shown to be IgG antibody. Results of the study demonstrated that there is good correlation between the inhibitory activity of immune serum, parasite growth in vitro, the in vivo response to challenge, and the indirect fluorescent antibody titer.     

Experimental American leishmaniasis and Chagas'' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi

, and 1988. Experimental American leishmaniasis and Chagas' disease in the Brazilian squirrel monkey: cross immunity and electrocardiographic studies of monkeys infected with Leishmania braziliensis and Trypanosoma cruzi. International Journal for Parasitology 18: 1053–1059. Adult, laboratory-bred squirrel monkeys (Saimiri sciureus) previously infected with either Leishmania braziliensis braziliensis or L. b. panamensis were challenge infected with blood-form trypomastigotes of Trypanosoma cruzi (Brazil strain). Monkeys previously infected with T. cruzi were challenged with stationary phase promastigote forms of L. b. braziliensis. Monkeys were examined during the course of challenge for evidence of infection, electrocardiographic alterations and parasite-specific antibody responses. T. cruzi epimastigotes were cultured from the blood of monkeys up to 3 months after challenge with this parasite. Unulcerated cutaneous lesions appeared and persisted in monkeys challenged with L. b. braziliensis. The formation of satellite lesions was observed in one monkey. Increased QRS intervals were not observed in T. cruzi challenged monkeys without prior cardiac irregularities and QRS left axis shifts were observed in only two of these monkeys. Elevated titers of parasite binding IgM and IgG specific for both T. cruzi and L. braziliensis were observed in all monkeys following challenge. These results indicate that prior infection with T. cruzi or L. braziliensis does not protect against heterologous challenge infection with these organisms. However, prior infection with Leishmania parasites may provide some protection against chagasic cardiopathies.     

Detection and quantification of variant specific antigen in the plasma of rats and mice infected with Trypanosoma brucei brucei

Variant specific antigen (VSA), the principal constituent of the surface coat of salivarian trypanosomes, was detected by gel immunoassays in the plasma of rats and mice infected with Trypanosoma brucei brucei. The quantity of VSA in plasma was measured in radial immunodiffusion tests using a monospecific antiserum and purified VSA as a standard. During the first peak of parasitemia, a statistically significant, linear relationship was determined between the number of parasites in the blood (in the range between 4 x 10(8) and 10(9)/ml) and the concentration of VSA in the plasma (28-320 microgram/ml). The VSA from parasites of the first peak was lost within 2 days of remission. Variant antigens of parasites constituting the second peak then began to appear in the plasma of infected rats. All plasma samples had been separated from parasites and blood cells within 15 min of blood collection. The pH of plasma was controlled with a buffered anticoagulant. No soluble parasite antigens, other than VSA, were detected in the plasma of infected hosts. The results of this study extend the observation that salivarian trypanosomes shed surface coat material during the course of infection. Thus, sloughed VSA may be the parasite product that has been hypothesized to cause the nonspecific lymphocyte proliferation, immunosuppression, and/or hypergammaglobulinemia which occur during African trypanosomiasis.     

The effect of BCG on the course of experimental Chagas' disease in mice

Experiments were done to determine the effect of BCG treatment on longevity, development of parasitemia, and in vivo distribution of ⁵¹Cr-labelled trypanosomes in C3H(He) female mice infected with a Brazil strain of Trypanosoma cruzi. BCG sensitization of mice was accomplished by a single IV injection of 3·0 mg (wet weight) of BCG. Twenty-one days after BCG injection mice were infected with 5 × 10⁴ blood-form trypomastigotes. Parasitemia determinations were made on alternate days during the experiment while in vivo distribution of exogenously supplied ⁵¹Cr-epimastigotes was made in groups of BCG or PBS stimulated mice on day 15 of the T. cruzi infection.It was found that BCG sensitization had no effect on longevity or parasitemia development in T. cruzi infected C3H(He) female mice. There were, however, some differences in the in vivo distribution of parasites between BCG treated and control mice. BCG stimulated mice accumulated greater numbers of radiolabelled trypanosomes in the kidneys and small intestines while PBS treated mice were found to have greater numbers of labelled parasites in the liver. Although no significant differences were observed in longevity of BCG or PBS treated mice, it was noted that BCG treated animals which were bled for parasitemia determinations lived significantly longer than those which were merely observed for longevity.     

William Trager: An Appreciation

SYNOPSIS. Additional information on host interactions with trypanosomatid membranes was obtained from studies of a monomorphic strain of Trypanosoma brucei harvested at peak parasitemia from intact and lethally irradiated rats. Pellets of trypanosomes were fixed briefly in glutaraldehyde and processed for thin section electron microscopy or freeze-cleave replicas. Observations of sectioned material facilitated orientation and comparison of details seen in replicas. Fracture faces of cell body and flagellar membranes as well as 3-dimensional views of the nuclear membrane were studied. Cell body membranes of 80% of the organisms from intact rats contained random arrays of intramembranous particles (IMP). Aggregated clusters of particles appeared on the fracture faces of 20% of the trypanosomes. Some of these membranes had nonrandomly distributed particles aligned in distinct rows on the outer fracture face of both cell body and flagellum. Many inner face fractures of the cell body membranes had a particle arrangement similar to the longitudinal alignment of cytoskeletal microtubules. No aggregated particle distribution was seen in membranes of trypanosomes harvested from lethally irradiated rats. Replicas of trypanosome pellets also had plasmanemes as a series of attached, empty, coated membrane vesicles. These structures were found in close association with, as well as widely separated from the parasites. The shedding of these vesicles and the variation of particles in cell body membranes are discussed in light of antibody-induced architectural and antigenic changes in surface properties of trypanosomatids. The convex face of the inner membrane of the nucleus also is covered with randomly arrayed particles. More IMP were observed on the inner than on the outer nuclear membranes. Images of nuclear pores were also seen. The importance of these structures in drug and developmental studies of trypanosomes is discussed. On fracture faces of the flagellar membrane there were miniature maculae adherentes, unique to the inner fracture face and occurring only at regions of membrane apposition between cell body and flagellum. Each cluster of particles exposed by the freeze-cleave method corresponds to an electron-dense plaque seen in thin section images. However, because of a unique fracture pattern, these plaques were not revealed on the apposing body membranes, as illustrated in thin sectioned organisms.     

IFN-gamma-dependent nitric oxide production is not linked to resistance in experimental African trypanosomiasis

Resistance to African trypanosomes is dependent on B cell and Th1 cell responses to the variant surface glycoprotein (VSG). While B cell responses to VSG control levels of parasitemia, the cytokine responses of Th1 cells to VSG appear to be linked to the control of parasites in extravascular tissues. We have recently shown that IFN-gamma knockout (IFN-gamma KO) mice are highly susceptible to infection and have reduced levels of macrophage activation compared to the wild-type C57BL/6 (WT) parent strain, even though parasitemias were controlled by VSG-specific antibody responses in both strains. In the present work, we examine the role of IFN-gamma in the induction of nitric oxide (NO) production and host resistance and in the development of suppressor macrophage activity in mice infected with Trypanosoma brucei rhodesiense. In contrast to WT mice, susceptible IFN-gamma KO mice did not produce NO during infection and did not develop suppressor macrophage activity, suggesting that NO might be linked to resistance but that suppressor cell activity was not associated with resistance or susceptibility to trypanosome infection. To further examine the consequence of inducible NO production in infection, we monitored survival, parasitemia, and Th cell cytokine production in iNOS KO mice. While survival times and parasitemia of iNOS KO mice did not differ significantly from WT mice, VSG-specific Th1 cells from iNOS KO mice produced higher levels of IFN-gamma and IL-2 than cells from WT mice. Together, these results show for the first time that inducible NO production is not the central defect associated with susceptibility of IFN-gamma KO mice to African trypanosomes, that IFNgamma-induced factors other than iNOS may be important for resistance to the trypanosomes, and that suppressor macrophage activity is not linked to either the resistance or the susceptibility phenotypes.     

Trypanosoma gambiense: immunity with thymic cell transfer in mice.

This report deals with the enhanced agglutinin production and protection in thymectomized, lethally irradiated mice (TI-mice) with transferred thymic cells from mice immune to T. gambiense. Such mice, when sensitized with trypanosome antigen showed protection against experimental infection and also produced agglutinins. Thymic cells from cortisone-treated immune mice were able to induce the production of agglutinins in TI-mice subsequently injected with antigen. However, these agglutinin titers were very low. In bovine serum albumin gradient centrifugation experiments, agglutinin production could be efficiently induced by inoculation of TI-mice with a rather high density thymic cell subpopulation taken from immune mice. Fractionated by Sephadex G-200, the agglutinins displayed a division into two parts, a first and second peak. The main agglutination reaction was seen in the first or macroglobulin peak. In the fractionation of serum by DEAE-cellulose column chromatography, agglutinins were eluted in two parts, the 0.0175 M and 0.4 M effluents. The agglutination by the 0.4 M effluent was much stronger than that of the 0.0175 M effluent, in agreement with the gel filtration results. The sera containing agglutinins were able to enhance the phagocytosis of trypanosomes by cultured macrophages from the peritoneal cavity of normal and irradiated mice. Delay of parasitemia was evident in some of the TI-mice having detectable agglutinins. The delayed parasitemia resulted from antigenically altered trypanosomes which were able to withstand the lethal factors of TI-mice. Transplantation of thymic cells was considered to be responsible for agglutinins induced by the antigenic stimulation in TI-mice and for protection against experimental infection.     

Trypanosoma lewisi: termination of pregnancy in the infected rat

Trypanosoma lewisi has previously been described as a nonpathogenic parasite of the rat, but these experiments demonstrate that both embryonal and maternal death may occur in the pregnant rat after infection with this parasite.Rats infected early in the first week of pregnancy resorbed their young with little apparent difficulty, and exhibited parasitemia curves typical of nonpregnant infected females of similar age.Rats infected late in the first week of pregnancy experienced greater difficulty resorbing the young, with half of the females dying shortly before parturition. The parasitemia counts were also similar to those of nonpregnant infected rats.The majority of rats infected during the midterm of pregnancy died at the time of parturition, without giving birth to their young. The number of parasites in these animals was abnormally high compared to nonpregnant infected females. Unusually large numbers of dividing trypanosomes were present in the placentae of these animals, many of them containing 8–16 nuclei and kinetoplasts.Animals infected during the last week of pregnancy gave birth to litters of normal size with little apparent difficulty, and had extremely low parasite counts.The hematocrits of all groups of infected animals showed a decrease at the time of peak parasitemia, and the hematocrits of all groups of pregnant rats showed a decrease at the time of birth, except for those infected when day 2 pregnant. These animals completely resorbed their young. The weight losses of rats infected on day 2 and day 6 of pregnancy reflected a termination of pregnancy.     

Some Quantitative Aspects of the Adoptive Transfer of Immunity to Plasmodium berghei with Immune Spleen Cells

SYNOPSIS. Some of the parameters concerned in the adoptive transfer of immunity to P. berghei in rats have been studied. Immunity was not transferred efficiently until about 10 days after recovery of donor rats had commenced, but thereafter was very effective, even after the infection appeared to have been sterilized. Animals protected by a standard dose of cells from immune spleens but challenged with different doses of parasites attained a parasitemia of about 5% at different times, but all overcame the infection at the same time. Animals protected by different doses of cells from immune spleens and challenged with a standard dose of parasites, attained a parasitemia of about 5% simultaneously but the time taken to control the infection was inversely proportional to the dose of protective cells. Up to a parasitemia of about 5% there was no difference in the multiplication rate of parasites in control animals, in animals which were not effectively protected and in protected animals. Beyond a parasitemia of about 5% there was no difference in the multiplication rate of parasites in control animals and in animals which were not effectively protected. It is suggested that there is a critical period at a parasitemia of about 5% when the level of the immune response determines the fate of the host. At that stage the immune response may be inadequate, or possibly exhausted, and the parasite will then continue to multiply unchecked. Saturation of reticulocytes with parasites at a level of about 5% total parasitized red cells probably gives the host a respite which may allow the adoptively transferred cells to control the infection.     

Trypanosoma congolense. 3. Serological responses of experimentally infected cattle

A complement fixation (CF) test for the diagnosis of Trypanosome congolense infection in cattle was developed and compared with the indirect fluorescent antibody (IFA) test.Serological investigations were made with cattle immunized with irradiated T. congolense and challenged with untreated T. congolense. Trypanosomal antibodies were demonstrated by the CF test. The results indicated good specificity and sensitivity between the CF method and the IFA test. The CF test also afforded easier reading of results than the IFA test; however, antigen preparation was more difficult in the former.The serological responses detected by the IFA and CF test appeared to be influenced by early variations of parasitemia, although no correlation appeared to exist between titer and parasitemia at later stages of the infection. Antibodies were detected in animals which received injections of irradiated T. congolense prior to challenge with viable organisms.     

Experimental infections with African trypanosomes: IV. Immunization of cattle with gamma-irradiated Trypanosoma rhodesiense

Cattle immunized with gamma-irradiated Trypanosoma rhodesiense were protected against a challenge inoculation of unirradiated trypanosomes given 1 wk later. These animals were still resistant when rechallenged after 8 mo and some residual immunity persisted for 14 mo after immunization. Animals which had undergone self-cure after infection were resistant when challenged 14 mo later. No resistance was observed in animals challenged with a heterologous strain of T. rhodesiense. The infections observed in unprotected bovines were of a mild nature. Leukopenia and fever were common early in the course of infection, but no anemia was evident at any time.