Efficacy of Coxiella burnetii and its chloroform-methanol residue (CMR) fraction against Rift Valley fever virus infection in mice

Strains of Coxiella burnetii phase I and II whole cells (WC-I and WC-II) or whole cell fractions were assessed for their potential to induce long-lasting protection in endotoxin-non-responder C3H/HeJ or CD-1 mice against Rift Valley fever (RVF) virus challenge. Among the whole cell fractions, only the chloroform-methanol residue (CMR), administered as a single dose (100 micrograms per mouse) 24 h before viral challenge, effectively protected 100% of the mice from RVF virus; the CMR of the Ohio strain of C. burnetii was not protective. Most of the RVF virus-infected mice treated with other C. burnetii cell fractions died, although their times to death varied. Lipopolysaccharide (LPS) associated with CMR preparations used in these studies, did not protect against RVF virus challenge. A single dose of 100 micrograms of CMR given 24 h before viral challenge completely eradicated 4-5 logs of RVF virus in the serum, liver, spleen, and central nervous system. Compared to several other immunomodulators, CMR was an equally effective antiviral agent. Efficacy of CMR of both Henzerling and Ohio strains disappeared or was marginal when treatment was initiated 2-3 days before RVF viral challenge, even when a second or a third dose of CMR was administered after challenge. A single dose of liposome-encapsulated CMR to RVF virus-infected mice extended the range of therapeutic efficacy of this biologically active component of C. burnetii to 4 days before infection.     

Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques

The authors examined the efficacy of Bacillus anthracis protective antigen (PA) combined with adjuvants as vaccines against an aerosol challenge of virulent anthrax spores in rhesus macaques. Adjuvants tested included i) aluminum hydroxide (Alhydrogel), ii) saponin QS-21 and iii) monophosphoryl lipid A (MPL) in squalene/lecithin/Tween 80 emulsion (SLT). Animals were immunized once with either 50 micrograms of recombinant PA plus adjuvant, or with Anthrax Vaccine Adsorbed (AVA), the licensed human anthrax vaccine. The serological response to PA was measured by enzyme linked immunosorbent assay. Lymphocyte proliferation and serum neutralization of in vitro lethal toxin cytotoxicity were also assayed. In all vaccine groups, anti-PA IgM and IgG titers peaked at 2 weeks and 4-5 weeks postimmunization, respectively. Five weeks postimmunization, animals in all vaccine groups demonstrated PA-specific lymphocyte proliferation and sera that neutralized in vitro cytotoxicity. Six weeks after immunization, the animals were challenged by aerosol with approximately 93 LD50 of virulent anthrax spores. Animals were bled daily for 1 week to monitor bacteremia, and deaths were recorded. Anti-PA ELISA titers in all groups of immunized animals were substantially increased 2 weeks after challenge. One dose of each vaccine provided significant protection (> 90%) against inhalation anthrax in the rhesus macaques.     

Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE)

We report a case of acute glomerulonephritis associated with acute Q fever. An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy. Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis. Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody. Other known causes of glomerulonephritis were excluded. Most reports of renal complications of C. burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever. Renal involvement in patients with acute C. burnetii infection has been rarely described. Glomerulonephritis should be recognized as a complication of acute C. burnetii infection and endocarditis due to chronic Q fever.     

Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine

In anticipation of future combination vaccines, a recombinant class 3 porin (rPorB) of group B meningococci was evaluated as an alternative carrier protein for a Haemophilus influenzae type b (Hib) polyribosylribotol phosphate (PRP) conjugate vaccine. The use of rPorB may avoid undesirable immunologic interactions among vaccine components, including epitopic suppression from conventional carriers (e.g. tetanus toxoid [TT]), as well as provide desirable immunomodulatory effects. Rats were found to be more reliable and consistent than mice or guinea pigs for studying antibody responses to the Hib conjugates. Different Hib conjugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reductive amination to TT or rPorB, were compared in rats. Commercially available, licensed vaccines, HbOC (HibTITER) and PRP-T (OmniHib), were used as reference controls. Maximum geometric mean ELISA IgG titers were obtained in rats after only two doses, showing booster effects for all. However, Hib-rPorB immunization consistently resulted in responses that were 1-2 orders of magnitude greater than those for the other conjugates, including the licensed control vaccines. A maximum 4600-fold rise was observed for Hib-rPorB after two doses, and, unlike the other conjugates, a 100% response rate was always achieved without adjuvant. These results warrant further investigation of Hib-rPorB in combination with DTaP.     

Influence of pentoxifylline on fevers induced by bacterial lipopolysaccharide and tumor necrosis factor-alpha in guinea pigs

In guinea pigs intraperitoneal (i.p.) injections of 50 mg/kg pentoxifylline had no influence on abdominal temperature while higher doses of pentoxifylline caused a hypothermic response lasting for 2-3 h. Administration of 50 mg/kg pentoxifylline 1 h before intramuscular (i.m.) injections of 20 micrograms/kg bacterial lipopolysaccharide reduced the lipopolysaccharide-induced production of endogenous tumor necrosis factor-alpha (TNF-alpha) by 68%. The second phase of lipopolysaccharide-induced fever was significantly attenuated by pretreatment with 50 mg/kg pentoxifylline, a dose which had, per se, no influence on core temperature of guinea pigs. The thermal response of guinea pigs to administration of exogenous TNF-alpha was not modulated by pretreatment with pentoxifylline. Intra-arterial infusions with 5 micrograms/kg TNF-alpha, a dose which yielded the same circulating TNF bioactivity as i.m. injections of 20 micrograms/kg lipopolysaccharide, induced a biphasic febrile response. The magnitude and duration of TNF-induced fever were the same whether guinea pigs were pretreated with pentoxifylline or with 0.9% saline. The results indicate that endogenous formation of TNF-alpha may contribute to the development of fever induced by lipopolysaccharide, but is not its only mediator, since the first phase of lipopolysaccharide-induced fever was not altered by the blockade of TNF production.     

Differences in eosinophil migration into the lungs following inhaled antigen challenge of parasite-naive guinea pigs with genetically determined differences in responsiveness to a gastrointestinal nematode parasite

Parasite-naive guinea pigs with genetically determined differences in responsiveness to infection with the gastrointestinal nematode parasite Trichostrongylus colubriformis were sensitised to ovalbumin and later challenged by exposure to an ovalbumin aerosol. The resultant cellular migration into the lungs was assessed by histological examination of the lungs and enumeration of cells in bronchoalveolar lavage fluid 24 h, 72 h and 7 days later. Compared with parasite-low-responder guinea pigs, there were approximately 10 times more eosinophils in lavage fluid from parasite-high-responder animals but similar numbers of neutrophils.     

The importance of MHC-I and MHC-II responses in vaccine efficacy against lethal herpes simplex virus type 1 challenge

To investigate the importance of major histocompatability complex (MHC) class I- and MHC class II-dependent immune responses in herpes simplex virus-1 (HSV-1) vaccine efficacy, groups of beta 2% (MHC I-) and Ab% (MHC II-) mice were inoculated with various vaccines, and then challenged intraperitoneally with HSV-1. Following vaccination with either live avirulent HSV-1, expressed HSV-1 glycoprotein D (gD), or a mixture of seven expressed HSV-1 glycoproteins (7gPs), Ab% (MHC-II-) mice developed no enzyme-linked immunosorbent assay (ELISA) or neutralizing antibody titres. In contrast, significant ELISA and neutralizing antibody titres were induced in beta 2m% (MHC-I-) mice by all three vaccines. The neutralizing antibody titres were similar for all three vaccines, but were only approximately 1/4 to 1/3 of that developed in C57BL/6 (parental) mice vaccinated with the same antigens. All three vaccines protected 100% of the wild-type C57BL/6 mice against lethal challenge with 2 x 10(7) plaque-forming units (PFU) of HSV-1. The live virus vaccine and the 7gPs vaccine also protected 80% of the beta 2m% mice against the same lethal HSV-1 challenge dose. In contrast, in Abo/o mice, none of the vaccines provided significant protection against the same lethal challenge dose of HSV-1. However, at a lower challenge dose of 2 x 10(6) PFU, all three vaccines protected 70-80% of the vaccinated Ab% mice (compared to only 10% survival in mock vaccinated controls). Thus, vaccination provided some protection against lethal HSV-1 challenge in both beta 2m% and Ab% mice; however, the protection was less than that seen in the parental C57BL/6 mice. In addition, Ab% mice were less well protected by vaccination than were beta 2m% mice. Our results suggest that (1) both MHC-I and MHC-II are involved in vaccine efficacy against HSV-1 challenge; (2) both types of responses must be present for maximum vaccine efficacy: and (3) the MHC-II-dependent immune response appeared to be more important than the MHC-I-dependent immune response for vaccine efficacy against HSV-I challenge.     

201Tl SPECT for suspected lung cancer in a case of a systemic arterial supply to the lung without sequestration

BACKGROUND: Q fever endocarditis is a life-threatening disease for which the diagnosis is usually based on serology. The major microbiologic criterion for the diagnosis of infectious endocarditis (two separate positive blood cultures) cannot be achieved in most routine laboratories because of the biohazard associated with the culture of Coxiella burnetii, the etiological agent of Q fever. PURPOSE: Recently, new criteria for the diagnosis of infectious endocarditis have been proposed, and in this study we attempted to assess the suitability of these criteria specifically for the diagnosis of Q fever endocarditis. PATIENTS AND METHODS: To achieve this aim, we first selected from our series 20 recent cases in whom endocarditis had been confirmed following valvular pathological examination, and for whom microbiological evidence for the involvement of C burnetii was available. Then, we applied the criteria proposed by the Duke Endocarditis Service (ie, C burnetii positive serology being considered a minor criterion) to this cohort of patients but excluding pathological findings. Although the Duke Endocarditis Service criteria confirmed diagnosis in 16 of the patients, 4 were misclassified as "possible" cases (20%). However, when the Q fever serological results (using an 1/800 antiphase I immunoglobulin G cut off) and single blood culture results were changed from minor to major diagnostic criteria, endocarditis was confirmed in them all. A second time, prospectively, we applied the Duke Endocarditis Service criteria to a further 5 patients affected with Q fever endocarditis. Strict application of these criteria resulted in 1 of the 5 being misdiagnosed. Applying the suggested modification for C burnetii results, all 5 were confirmed as having infectious endocarditis. CONCLUSION: We propose that the modifications discussed in this study be applied to the Duke Endocarditis Service criteria in order that the diagnosis of C burnetii induced endocarditis is improved.     

Isolation of Coxiella burnetii from dairy cattle and ticks, and some characteristics of the isolates in Japan

Coxiella burnetii was isolated from raw milk (36/214, 16.8%) and uterus swab samples (13/61, 21.3%) originating from dairy cattle with reproductive disorders, aborted bovine fetus samples (2/4, 50%), mammary gland samples (4/50, 8%) originating from healthy dairy cattle, and tick samples (4/15, 26.7%) originating from 2 pastures. Fifty-nine strains had various degrees of pathogenicity, high (8; 13.6%), moderate (28; 47.5%) and low (23; 39%), for guinea pigs. The results of isolation suggested a high prevalence of Coxiella infection in dairy cattle with reproductive problems in Japan. Twelve strains (7, 2 and 3 strains from cattle, ticks and humans, respectively) and the reference Nine Mile strain of phases I and II were propagated in both yolk sacs of embryonated hen eggs and Buffalo green monkey (BGM) cell cultures. Protein profiles of these strains were similar to those of the reference strain of phase I. Lipopolysaccharide (LPS) profiles of 12 strains were similar to those of the reference strain of phase I and different from those of the reference strain of phase II. The LPS profiles of 12 strains suggested that these strains are associated with an acute form of Q fever.     

Purification, potency, and efficacy of the botulinum neurotoxin type A binding domain from Pichia pastoris as a recombinant vaccine candidate

Recombinant botulinum neurotoxin serotype A binding domain [BoNT/A(Hc)], expressed in Pichia pastoris, was developed as a vaccine candidate for preventing botulinum neurotoxin type A (BoNT/A) intoxication. After fermentation and cell disruption, BoNT/A(Hc) was purified by using a three-step chromatographic process consisting of expanded-bed chromatography, Mono S cation-exchange chromatography, and hydrophobic interaction chromatography. Two pools of immunogenic product were separated on the Mono S column and processed individually. Both products were more than 95% pure and indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Each protein was assayed for potency in mice at immunogen doses ranging from 2.4 ng to 10 microg, followed by challenge with 1,000 mouse intraperitoneal 50% lethal doses (i.p. LD50) of BoNT/A. The calculated 50% effective dose for both peaks was approximately 0.1 microg/mouse. Peak 1 was evaluated further in a mouse efficacy assay. Mice were injected either once, twice, or three times at five different doses and subsequently challenged with 100,000 mouse i.p. LD50 of BoNT/A. In general, multiple injections protected better than one, with complete or nearly complete protection realized at doses of >/=0.5 microg/mouse. Serum neutralization and ELISA titers were also determined. Tellingly, 82 of 83 mice with antibody titers of >/=1, 600, as measured by ELISA, survived, but only 6 of 42 mice with titers of 相似文献   

Effect on viraemia of an American and a European serotype PRRSV vaccine after challenge with European wild-type strains of the virus

Three groups of 10 pigs were vaccinated with an American serotype porcine reproductive and respiratory syndrome virus (PRRSV) vaccine and three groups of 10 pigs were vaccinated with a European serotype PRRSV vaccine. A control group of 12 pigs was left unvaccinated. Four weeks after vaccination the PRRSV-specific antibody titres were determined and each group was challenged with either a Spanish, German or Dutch PRRSV wild-type strain. The serological responses four weeks after vaccination confirmed that the two vaccines were of different serotypes. Vaccination with the American serotype vaccine hardly reduced the level of viraemia after challenge with the European PRRSV wild-type strains, and only after challenge with the Spanish PRRSV strain was a moderate, statistically significant reduction in viraemia observed. In contrast, after vaccination with the European serotype vaccine, viraemia was completely suppressed after challenge with the German PRRSV isolate and almost completely suppressed after challenge with the Spanish and Dutch PRRSV isolates.     

Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene

The authors have designed and constructed a plant-optimize synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 micrograms LT-B, or gavaged weekly with 5 micrograms of LT-B from recombinant E. coli. One week after the third dose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 micrograms LT, and protection assessed by comparing the gut/carcass mass ratios. Although none of the mice were completely protected, the higher dose potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LT-B is feasible.     

International bank for foot-and-mouth disease vaccine: assessment of Montanide ISA 25 and ISA 206, two commercially available oil adjuvants

The International Vaccine Bank at Pirbright has recently installed large-scale vaccine formulation equipment for the preparation of oil-adjuvanted vaccines. Such vaccines are claimed to offer a number of advantages over Al(OH)3, particularly their ability to raise better immunity in pigs. This paper reports on the potency in pigs, cattle and guinea-pigs of foot-and-mouth disease vaccines prepared with two novel oil adjuvants, Montanide ISA 25 and 206 (Seppic, Paris). The results indicate that vaccines adjuvanted with these oils retain potency for a longer period than our conventional aqueous formulation, following storage at +4 degrees C, and elicit good antibody responses in both pigs and cattle regardless of injection route. In addition they gave no evidence of toxicity or prolonged pyrexia following their administration. Local reactions at the site of inoculation were not observed in cattle vaccinated intramuscularly, even following a booster dose. Pigs vaccinated intramuscularly only showed local reactions if the volume administered exceeded the 2.0 ml dose or the animals received a second vaccination. These observations on the efficacy of such oil formulated vaccines suggest that they have potential as an alternative to the current aqueous formulation.     

Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.     

Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin

A small study was performed to examine whether the instillation of ricin toxoid vaccine into the lungs of Porton rats offered protection from lethal effects of subsequent intratracheal challenge with ricin toxin. Further the immune response to liposomally-encapsulated vaccine and the protection offered was compared with vaccine either adsorbed to Alhydrogel adjuvant or as a simple aqueous solution. The formaldehyde-treated ricin toxin vaccine (RTV) was administered at two dose levels, 500 and 100 micrograms kg-1 body weight to groups of rats, on two occasions by intratracheal instillation. Liposomally-encapsulated vaccine (LRTV) produced a higher titre of ricin-specific antibodies than Alhydrogel-vaccine (ARTV) and vaccine solution. When challenged with 3 LD50 of ricin by intratracheal instillation 7 weeks after the second vaccine instillation, all rats in both LRTV dose groups survived with minimal signs of incapacitation. Analysis of antibody secretion by spleen cells, 14 days post challenge, showed that the IgG isotype in the LRTV group was significantly higher than that in the ARTV and RTV groups and also that the proportion of specific IgA in lung fluid was higher in the LRTV group than in the ARTV and RTV groups. The results of this study indicate that effective vaccinations against inhaled ricin could be achieved with liposomally-encapsulated ricin toxoid, via the lung and should be investigated further.     

Prediction of microcirculatory oxygen transport by erythrocyte/hemoglobin solution mixtures

Vaccination with naked DNA may be an alternative to conventional vaccines because it combines the efficacy of attenuated vaccines with the biological safety of inactivated vaccines. We recently showed that the vaccination with naked DNA coding for the immunorelevant glycoprotein D (gD) of pseudorabies virus (PRV) induced both antibody and cell-mediated immunity in pigs and provided protection against challenge infection. To determine whether the efficacy of the naked DNA vaccination against PRV could be improved, we compared three sets of variables. First, the efficacy of the naked DNA vaccine coding only for the immunorelevant gD was compared with a cocktail vaccine containing additional plasmids coding for two other immunorelevant glycoproteins, gB and gC. Second, the intramuscular route of vaccination was compared with the intradermal route. Third, the commonly used needle method of inoculation was compared with the needleless Pigjet injector method. Five groups of five pigs were vaccinated three times at 4-weeks intervals and challenged with the virulent NIA-3 strain of PRV 6 weeks after the last vaccination. Results showed that although the cocktail vaccine induced stronger cell-mediated immune responses than the vaccine containing only gD plasmid, both vaccines protected pigs equally well against challenge infection. Intradermal inoculation with a needle induced significantly stronger antibody and cell-mediated immune responses and better protection against challenge infection than intramuscular inoculation. Our data show that the route of administering DNA vaccines in pigs is important for an optimal induction of protective immunity.     

An aromatic-dependent mutant of the fish pathogen Aeromonas salmonicida is attenuated in fish and is effective as a live vaccine against the salmonid disease furunculosis

Aeromonas salmonicida is the etiological agent of furunculosis in salmonid fish. The disease is responsible for severe economic losses in intensively cultured salmon and trout. Bacterin vaccines provide inadequate protection against infection. We have constructed an aromatic-dependent mutant of A. salmonicida in order to investigate the possibility of an effective live-attenuated vaccine. The aroA gene of A. salmonicida was cloned in Escherichia coli, and the nucleotide sequence was determined. The codon usage pattern of aroA was found to be quite distinct from that of the vapA gene coding for the surface array protein layer (A layer). The aroA gene was inactivated by inserting a fragment expressing kanamycin resistance within the coding sequence. The aroA::Kar mutation was introduced into the chromosome of virulent A. salmonicida 644Rb and 640V2 by allele replacement by using a suicide plasmid delivery system. The aroA mutation did not revert at a detectable frequency (< 10(-11). The mutation resulted in attenuation when bacteria were injected intramuscularly into Atlantic salmon (Salmo salar L.). Introduction of the wild-type aroA gene into the A. salmonicida mutants on a broad-host-range plasmid restored virulence. A. salmonicida mutant 644Rb aroA::Kar persisted in the kidney of brown trout (Salmo trutta L.) for 12 days at 10 degrees C. Vaccination of brown trout with 10(7) CFU of A. salmonicida 644Rb aroA by intraperitoneal injection resulted in a 253-fold increase in the 50% lethal dose (LD50) compared with unvaccinated controls challenged with a virulent clinical isolate 9 weeks later. A second vaccination after 6 weeks increased the LD50 by a further 16-fold.     

The optimization of helper T lymphocyte (HTL) function in vaccine development

Helper T lymphocyte (HTL) responses play an important role in the induction of both humoral and cellular immune responses. Therefore, HTL epitopes are likely to be a crucial component of prophylactic and immunotherapeutic vaccines. For this reason, Pan DR helper T cell epitopes (PADRE), engineered to bind most common HLA-DR molecules with high affinity and act as powerful immunogens, were developed. Short linear peptide constructs comprising PADRE and Plasmodium-derived B cell epitopes induced antibody responses comparable to more complex multiple antigen peptides (MAP) constructs in mice. These antibody responses were composed mostly of the IgG subclass, reactive against intact sporozoites, inhibitory of schizont formation in liver invasion assays, and protective against sporozoite challenge in vivo. The PADRE HTL epitope has also been shown to augment the potency of vaccines designed to stimulate a cellular immune response. Using a HBV transgenic murine model, it was found that CTL tolerance was broken by PADRE-CTL epitope lipopeptide, but not by a similar construct containing a conventional HTL epitope. There are a number of prophylactic vaccines that are of limited efficacy, require multiple boosts, and/or confer protection to only a fraction of the immunized population. Also, in the case of virally infected or cancerous cells, new immunotherapeutic vaccines that induce strong cellular immune responses are desirable. Therefore, optimization of HTL function by use of synthetic epitopes such as PADRE or pathogen-derived, broadly crossreactive epitopes holds promise for a new generation of highly efficacious vaccines.     

Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice

We have expressed the proline-rich antigen (PRA) from Coccidioides immitis in Escherichia coli and evaluated its potential as a vaccine candidate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the recombinant protein (rPRA) revealed two bands, which exhibited virtually identical primary amino acid sequences. T cells from rPRA-immunized BALB/c mice showed a significant in vitro proliferative response to rPRA. A small but statistically significant proliferative response was also induced by rPRA in T cells from mice immunized with whole-cell coccidioidal vaccines. BALB/c mice immunized with rPRA and challenged intraperitoneally with virulent C. immitis had a greatly reduced fungal burden in their lungs and spleens compared to unvaccinated mice. The number of organisms in the lungs was reduced 500-fold, and similar reductions were observed in the spleens of immunized mice. These studies support the continued development of rPRA as a candidate vaccine for prevention of coccidioidomycosis.     

Q fever (Coxiella burnetii) investigations in dairy cattle: challenge of immunity after vaccination

The immunity of Holstein-Friesian dairy cows vaccinated against Coxiella burnetii was challenged with 4 X 10(8) infective guinea pig doses of viable rickettsiae. Cows that were vaccinated had normal full-term calves, whereas 2 nonvaccinated cows aborted late in pregnancy. Intrauterine infection of the fetus was indicated by recovery of the organism from tissues of the fetus. Coxiella burnetii was recovered from milk, colostrum, and placenta of vaccinated and nonvaccinated cows after challenge inoculation, but the rickettsiae recovered were as many as 1,000 times more numerous in nonvacinated cows.