High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV patients

Clostridium difficile is the most commonly identified bacterial cause of nosocomial and HIV-related diarrhea. In many developing countries, antibiotic access is unregulated. Nigeria has the third highest HIV burden worldwide. Due to perceptions of low prevalence and resource incapacity, patients with diarrhea are not tested for toxinogenic C. difficile infection (CDI). In this pilot study which included 97 HIV-positive patients at two hospitals in Nigeria, the estimated prevalence of CDI was 43% and 14% for in-patients and out-patients respectively. HIV-positive out-patients were more likely to have toxinogenic CDI than non-HIV out-patients (P = 0.007, Fisher's exact test).     

Evaluation of recombinant Mycoplasma hyopneumoniae P97/P102 paralogs formulated with selected adjuvants as vaccines against mycoplasmal pneumonia in pigs

Pig responses to recombinant subunit vaccines containing fragments of eight multifunctional adhesins of the Mycoplasma hyopneumoniae (Mhp) P97/P102 paralog family formulated with Alhydrogel^® or Montanide™ Gel01 were compared with a commercial bacterin following experimental challenge. Pigs, vaccinated intramuscularly at 9, 12 and 15 weeks of age with either of the recombinant formulations (n = 10 per group) or Suvaxyn^® M. hyo (n = 12), were challenged with Mhp strain Hillcrest at 17 weeks of age. Unvaccinated, challenged pigs (n = 12) served as a control group. Coughing was assessed daily. Antigen-specific antibody responses were monitored by ELISA in serum and tracheobronchial lavage fluid (TBLF), while TBLF was also assayed for cytokine responses (ELISA) and bacterial load (qPCR). At slaughter, gross and histopathology of lungs were quantified and damage to epithelial cilia in the porcine trachea was evaluated by scanning electron microscopy. Suvaxyn^® M. hyo administration induced significant serological responses against Mhp strain 232 whole cell lysates (wcl) and recombinant antigen F3_P216, but not against the remaining vaccine subunit antigens. Alhydrogel^® and Montanide™ Gel01-adjuvanted antigen induced significant antigen-specific IgG responses, with the latter adjuvant eliciting comparable Mhp strain 232 wcl specific IgG responses to Suvaxyn^® M. hyo. No significant post-vaccination antigen-specific mucosal responses were detected with the recombinant vaccinates. Suvaxyn^® M. hyo was superior in reducing clinical signs, lung lesion severity and bacterial load but the recombinant formulations offered comparable protection against cilial damage. Lower IL-1β, TNF-α and IL-6 responses after challenge were associated with reduced lung lesion severity in Suvaxyn^® M. hyo vaccinates, while elevated pathology scores in recombinant vaccinates corresponded to cytokine levels that were similarly elevated as in unvaccinated pigs. This study highlights the need for continued research into protective antigens and vaccination strategies that will prevent Mhp colonisation and establishment of infection.     

Nosocomial diarrhea and Clostridium Difficile associated diarrhea in a Turkish University Hospital

Background

Clostridium difficile (C. difficile) is a well-established cause of nosocomial diarrhea. The aim of our study was to define the incidence of nosocomial diarrhea in our hospital and to determine the role of C. difficile. Additionally, the risk factors for nosocomial diarrhea and Clostridium difficile associated diarrhea (CDAD) were investigated.

Methods

We included all patients, 18 years of age or more, who were admitted to the Uludag Teaching Hospital between October 1, 2004 and February 1, 2005, and developed diarrhea at least three days after hospital admission. A case-control study was performed.

Results

The total incidence of nosocomial diarrhea was 0.6 per 1,000 hospitalization-days and 5 per 1,000 patients’ admissions. Previous use of chemotherapy was found to be an important predisposing factor for nosocomial diarrhea. The incidence of CDAD was 0.26 per 1,000 hospitalization-days and 2.1 per 1,000 admissions, comparable with incidence rates in Europe.CDAD was diagnosed in 43% of patients with nosocomial diarrhea. No severe cases of CDAD were diagnosed. A correlation was found between CDAD and antibiotic use before admission and during admission in univariate analysis. PCR ribotyping revealed four strains of PCR ribotype 002 and 1 strain of ribotype 012 out of 5 C. difficile strains available for extensive identification.

Conclusion

The incidence rates of nosocomial diarrhea and CDAD are not different than the usual incidence rates in Europe. C. difficile was the causative agent in 43% of patients with nosocomial diarrhea.     

Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response

A live oral cholera vaccine developed from a non-toxigenic Vibrio cholerae O1 El Tor strain VA1.3 was tested in a double-blind randomized placebo controlled study for safety and immunogenicity in 304 men aged between 16 and 50 years from Kolkata, India. A dose of 5 × 10⁹ CFU (n = 186) or a placebo (n = 116) containing the diluent buffer was administered. The vaccine did not elicit adverse events except in two vaccine recipients with mild diarrhoea and vomiting. None excreted the vaccine strain. Vibriocidal antibody response developed in 105/186 (57%) and 5/116 (4%) in vaccine and placebo recipients, respectively. In a subgroup, anti-CT antibody rose (≥2-folds) in 23/30 (77%) and 6/19 (32%) in vaccine and placebo recipients, respectively. These studies demonstrate that VA1.3 at a dose of 5 × 10⁹ is safe and immunogenic in adults from a cholera endemic region.     

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae prior to introduction of the 10-valent pneumococcal conjugate vaccine in Brazil, 2000-2007

This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine.The active hospital-based surveillance showed a decline in the annual incidence rates of pneumococcal meningitis during the period of study, from 1.12 cases to 0.83 cases/100,000 persons for all age groups (P < 0.001), with an overall case-fatality rate of 28.6% (113 of 395) for all patients and 41.9% (57 of 136) for those <5 years of age. Serotypes 14 (n = 55; 13.9%), 3 (n = 32; 8.1%), 23F (n = 32; 8.1%), 19F (n = 31; 7.8%), 6B (n = 30; 7.6%), 18C (n = 28; 7.1%), and 6A (n = 20; 5%) were the most prevalent serotypes. In patients <5 years the estimated projected coverage of 7-, 10- and 13-valent conjugate vaccines was 74.3%, 75.7% and 83.1%, respectively. Antimicrobial susceptibility testing revealed that 22.1% (n = 88) of isolates were non-susceptible to penicillin, 56% were non-susceptible to trimethoprim/sulphamethoxazole, and 29.6% were non-susceptible to tetracycline. Nonsusceptibility to penicillin and cefotaxime was detected solely among serotype 14 isolates (n = 4; 1%). This study provides an important baseline to assess the impact of conjugate vaccine implantation on the epidemiology of meningitis due to Streptococcus pneumoniae in Salvador, Brazil.     

Induction of protection in mice against a respiratory challenge by a vaccine formulated with the Chlamydia major outer membrane protein adjuvanted with IC31®

IC31^®, a novel adjuvant, has been shown to be effective by increasing the levels of IFN-γ in animal models when delivered with several antigens. Here, we tested the ability of IC31^®, to enhance the protective ability of the Chlamydia trachomatis native major outer membrane protein (nMOMP). BALB/c mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with nMOMP + IC31^®. Another group of animals was immunized with nMOMP + Alum and as a negative control mice were immunized with ovalbumin (Ova) + IC31^®. Animals immunized with nMOMP + IC31^® developed high Chlamydia-specific IgG titers. The serum levels of IgG1 were higher than those of the IgG2a. T cells, from the spleens of mice immunized with IC31^®-adjuvanted nMOMP demonstrated a strong lymphoproliferative reaction to Chlamydia elementary bodies (EB) compared with the groups immunized with nMOMP + Alum or Ova + IC31^®. A similar comparison between these groups of mice revealed that the levels of IFN-γ in the supernatants from stimulated T-cells were significantly higher in animals immunized with nMOMP + IC31^®. Following an intranasal challenge with C. trachomatis, the mice immunized with IC31^®-adjuvanted nMOMP showed significant protection. The change in body weight, an indication of the severity of the infection, was significantly less reduced in mice immunized with nMOMP + IC31^®. Furthermore, the weight of the lungs, as well as the pulmonary Chlamydia burden, was significantly lower in the animals immunized with nMOMP + IC31^® when compared with the groups immunized with nMOMP + Alum or with Ova + IC31^®. In conclusion, these results provide the rationale for further preclinical testing of IC31^® using other chlamydial antigens, and support the potential evaluation of this adjuvant in human vaccines against Chlamydia.     

Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant Hepatitis B vaccination

Probiotics have been shown to enhance specific immune responses to vaccines. We aim to assess the effect of probiotic supplementation on specific IgG antibody responses to Hepatitis B (HepB) vaccination in infants. Compared to controls, probiotic supplementation improved HepB surface antibody responses in subjects receiving monovalent doses of HepB vaccine at 0, 1 month and a DTPa–HepB combination vaccine at 6 months [placebo (n = 28): 187.97 (180.70–195.24), probiotic (n = 29): 345.70 (339.41–351.99) mIU/ml] (p = 0.069), but not those who received 3 monovalent doses [placebo (n = 68): 302.34 (296.31–308.37), probiotic (n = 77): 302.06 (296.31–307.81) mIU/ml] (p = 0.996). Probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules.     

Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia,hospitalisation, and mortality: Re-analysis of a randomised trial in The Gambia

Background

Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children.

Methods

We reanalysed data from a randomised placebo-controlled trial. Infants aged 6–51 weeks were allocated to three doses of nine-valent PCV (n = 8718) or placebo (n = 8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules.

Results

Predicted efficacy in the groups aged 6 weeks (n = 2467, 154 events) or 10 weeks (n = 2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19–43%) and 33% (95% CI 21–44%), against hospitalisation 14% (95% CI 3–23%) and 17% (95% CI 7–26%), and against mortality 17% (95% CI −3 to 33%) and 16% (95% CI −3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n = 2701, 133 events) or 2 months (n = 1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20–44%) and 36% (95% CI 24–46%), against hospitalisation 15% (95% CI 5–24%) and 18% (95% CI 8–27%), and against mortality 17% (95% CI −2 to 33%) and 13% (95% CI −8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules.

Conclusions

We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.     

Pneumocystis jirovecii colonization and infection among non HIV-infected patients

Objective and method

The epidemiology of pneumocystosis has changed in the last decade with a decreased incidence in HIV infected patients, and the emerging concept of Pneumocystis colonization. The study objective was to describe Pneumocystis infection as well as colonization among non-HIV infected patients in the Rouen teaching hospital and cancer institute. A retrospective study was made of all patients with a positive respiratory sample for Pneumocystis jirovecii between January 1, 2000 and June 6, 2007.

Results

Fifty-four cases were reported (46 cases of pneumocystosis and eight of asymptomatic carriage) and an increasing yearly incidence over the study period was observed. Underlying diseases for pneumocystosis were haematological malignancies (n = 25; 54%), organ transplantation (n = 8; 17.4%), inflammatory disorders (n = 6; 13%), and solid cancer (n = 5; 10.8%). Sixty-five per cent of patients were under long-term steroid therapy. The overall mortality rate was 21.4%. The CD4 count for 26 patients, ranged from 18 to 1449/mm³ (median: 107). Eight cases of asymptomatic carriage were reported with an underlying immunodepression (n = 6) and pulmonary disease (n = 2).

Discussion

The increasing incidence of pneumocystosis in immunosuppressed patients without AIDS is due to more frequent favorable conditions and progress of diagnostic tools. The clinical presentations are severe. Prophylaxis is badly codified because there is no threshold value for CD4 count. Colonization could present a warning value.     

T-cell-derived cytokines,nitric oxide production by peripheral blood monocytes and seric anti-Leishmania (Leishmania) chagasi IgG subclass patterns following immunization against canine visceral leishmaniasis using Leishvaccine and Leishmune

It is generally accepted that distinct cytokine expression by the cellular immune response plays a critical role during the outcome of experimental as well as natural canine visceral Leishmaniasis (CVL). Despite the fact that immunoprophylaxis of CVL has become an important control strategy and protective immunity has been reported upon immunization with whole as well as purified Leishmania antigens, the cytokine profile of T-cells triggered by anti-CVL vaccines still remain to be determined. Herein, we have developed a cross-sectional analysis of German Shepherd dogs submitted to vaccination protocols with Leishvaccine (n = 6) and Leishmune^® (n = 6). Our data identified distinct immunological profiles elicited by Leishvaccine and Leishmune^®, with the Leishvaccine triggering a mixed, IFN-γ and IL-4, cytokine pattern in addition to high levels of anti-Leishmania IgG1, whereas the Leishmune^® induced an immunological pattern characterized by enhanced levels of IFN-γ, NO and anti-Leishmania chagasi IgG2. It was important to notice that despite the distinct immunological patterns triggered by Leishvaccine and Leishmune^®, the ability of both immunobiologicals to activate T-cell-derived IFN-γ synthesis further suggesting their immunogenic potential against CVL. These findings added support to our hypothesis that both antigenic composition (whole antigen in Leishvaccine versus purified antigen in Leishmune^®) as well as the adjuvant nature (BGC and saponin) used for the vaccine formulation may count for the distinct activation pattern observed.     

A systematic review of experimental infections with enterotoxigenic Escherichia coli (ETEC)

Volunteer challenge with enterotoxigenic Escherichia coli (ETEC) has been used for four decades to elucidate the pathogenesis and immune responses and assess efficacy of various interventions. We performed a systematic review of these studies and a meta-analysis of individual patient-level data (IPD) from a subset of studies using standard methodology.We identified 27 studies of 11 ETEC strains administered to 443 naive subjects at doses from 1 × 10⁶ to 1 × 10¹⁰ colony forming units (cfu). Diarrhea attack rates varied by strain, dose and enterotoxin. Similar rates were seen at doses of 5 × 10⁸ to 1 × 10¹⁰ cfu with the three most commonly used strains B7A, E24377A, H10407. In IPD analysis, the highest diarrhea attack rates were seen with strains B7A, H10407 and E24377A. The H10407 induced significantly higher stool output than the other strains. Additionally, the rate of output was different across strains.The risk of diarrhea, abdominal cramps, nausea and headaches differed significantly by ETEC strain. An increased risk of nausea, abdominal cramps and headaches was seen for females. Baseline anti-LT IgG titers appeared to be associated with a decrease risk of diarrhea outcomes, a trend not seen with anti-LT IgA or seen consistently with anti-colonization factor antibodies. Neither early antibiotic treatment nor diarrhea duration significantly affected the frequency or magnitude of serologic responses.These studies have served as an invaluable tool in understanding disease course, pathogenicity, innate immune responses and an early assessment of product efficacy. When designing and planning experimental ETEC infection studies in this age of increased ethical scrutiny and growing appreciation of post-infectious sequelae, better understanding of available data is essential.     

Recombinant Liver Stage Antigen-1 (LSA-1) formulated with AS01 or AS02 is safe,elicits high titer antibody and induces IFN-γ/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection

Plasmodium falciparum Liver Stage Antigen 1 (LSA-1) is a pre-erythrocytic stage antigen. Our LSA-1 vaccine candidate is a recombinant protein with full-length C- and N-terminal flanking domains and two of the 17 amino acid repeats from the central repeat region termed “LSA-NRC.” We describe the first Phase I/II study of this recombinant LSA-NRC protein formulated with either the AS01 or AS02 adjuvant system. We conducted an open-label Phase I/II study. Thirty-six healthy malaria-naïve adults received one of four formulations by intra-deltoid injection on a 0 and 1 month schedule; low dose (LD) LSA-NRC/AS01:10 μg LSA-NRC/0.5 ml AS01 (n = 5), high dose (HD) LSA-NRC/AS01: 50 μg LSA-NRC/0.5 ml AS01 (n = 13); LD LSA-NRC/AS02: 10 μg LSA-NRC/0.5 ml AS02 (n = 5) and HD LSA-NRC/AS02: 50 μg LSA-NRC/0.5 ml AS02 (n = 13). Two weeks post-second immunization, the high dose vaccinees and 6 non-immunized infectivity controls underwent experimental malaria sporozoite challenge.     

Novel vector vaccine against Brucella abortus based on influenza A viruses expressing Brucella L7/L12 or Omp16 proteins: Evaluation of protection in pregnant heifers

The present study provides the first information about the protection of a novel influenza viral vector vaccine expressing the Brucella proteins ribosomal L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n = 10) or subcutaneous (n = 10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with Brucella abortus S19 (n = 10) or B. abortus RB51 (n = 10) and a negative (PBS + Montanide Gel01; n = 10) control group. Via both the conjunctival or subcutaneous route, evaluation of protectiveness against abortion, effectiveness of vaccination and index of infection (in heifers and their fetuses or calves) demonstrated the vector vaccine provided good protection against B. abortus 544 infection compared to the negative control group (PBS + Montanide Gel01) and comparable protection to commercial vaccines B. abortus S19 or B. abortus RB51.     

Oligomannose-coated liposome-entrapped dense granule protein 7 induces protective immune response to Neospora caninum in cattle

Neospora caninum is an intracellular protozoan parasite that causes abortion in cows. Vaccination is an important strategy for control of neosporosis, and a safe and effective vaccine suitable for cattle is required. Dense granule protein 7 of N. caninum (NcGRA7) is a secretory protein with high antigenicity in hosts. We demonstrated previously that NcGRA7 entrapped in liposomes coated with mannotriose (M3-NcGRA7) could induce a parasite-specific T-helper type 1 immune response and produce humoral antibodies that resulted in increased offspring survival and decreased infection in the brains of mice dams. In the present study, the efficacy of M3-NcGRA7 as a vaccine candidate against N. caninum has been evaluated in cattle (n = 12). Cattle were immunized with M3-NcGRA7 containing 50 μg (n = 4) or 200 μg NcGRA7 (n = 4) subcutaneously twice with a 4-week interval and all cattle including the non-immunized controls (n = 4) were inoculated with 10⁷ tachyzoites of Nc-1 strain 27 days after the second immunization and euthanized at 85–87 days post infection (dpi). In immunized cattle, NcGRA7-specific antibody production and IFN-γ production in PBMC was induced before challenge. At 3 dpi, body temperature and concentration of serum IFN-γ tended to be higher in control cattle than in the immunized cattle. Furthermore, the parasite load in the brain significantly decreased in cattle immunized with 50 μg M3-NcGRA7 compared with controls. These results suggest that M3-NcGRA7 can induce protective immune responses to N. caninum tachyzoites in cattle, which could lead to practical application of safe and effective subunit vaccines.     

Immunotherapy with the saponin enriched-Leishmune vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis

Leishmune^®, the first licensed vaccine for prophylaxis against canine visceral leishmaniasis (CVL) and is also immunotherapeutic when used with double saponin adjuvant concentration. The Leishmune^® therapeutic vaccine was assessed for immunotherapy (IT) in 31 infected dogs and for immunochemotherapy (ICT) in combination with allopurinol or amphotericinB/allopurinol, in 35 dogs. Compared to infected untreated control dogs, at month 3, both treatments increased the proportion of dogs showing intradermal response to Leishmania antigen to a similar extent (from 8 to 67%, in the IT and to 76%, in the ICT groups), and conversely reduced from 100 to 38% (IT) and to 18% (ICT) the proportion of symptomatic cases, from 54 to 12% (IT) and to 15% (ICT) the proportion of parasite evidence in lymph nodes and from 48 to 19% (IT) and 12% (ICT) the proportion of deaths, indicating that the immunotherapy with enriched-Leishmune^® vaccine promotes the control of the clinical and parasitological signs of CVL rendering most dogs asymptomatic although PCR positive. By month 8, negative lymph node PCR results were obtained in 80% of the ICT-treated dogs, but only in 33% of the IT group (p = 0.0253), suggesting that the combination of additional chemotherapy with Leishmune^®-enriched saponin vaccination abolished, not only the symptoms but also the latent infection condition, curing the dogs. The animals were followed up until 4.5 years after the beginning of the experiment and, compared to the untreated control group at month 3 (12/25 dogs; 48%), a decrease in the rate of CVL deaths was only seen after ICT treatment (7/35 dogs; 20%; 0.0273) but not after IT treatment (10/31 dogs; 32%; p = 0.278), pointing out an additional advantage of the ICT treatment with the enriched-Leishmune^® in the control and cure of CVL.     

Revaccination with Fendrix or HBVaxPro results in better response rates than does revaccination with three doses of Engerix-B in previous non-responders

Because non-response (<10 IU/l anti-HBs) after revaccination for hepatitis B occurs frequently (50%), this study aimed to provide evidence for a more effective revaccination regimen by comparing four different revaccinations: (1) three revaccinations with Engerix-B^® (n = 201); (2) one revaccination with Engerix-B^® (n = 37); (3) one revaccination with HBVaxPro-40^® (n = 108); (4) one revaccination with Fendrix^® (n = 39). The level of anti-HBs antibodies was determined with the AXSYM-MEIA system (Abbott, Chicago, USA). Using linear and logistic regression, the efficacy (antibody response) after the four revaccinations was compared. Analyses were corrected for age, sex, primary titre and time lag between last revaccination and the titre measurement. The height of the primary titre independently predicted antibody response. Compared to the revaccination scheme using three Engerix-B^® doses, revaccination with a single dose of HBVaxPro-40^® or Fendrix^® performed significantly better. The use of these highly potent vaccines should be considered when revaccinating hepatitis B vaccine non-responders.     

Comparison of two commercial vaccines against visceral leishmaniasis in dogs from endemic areas: IgG,and subclasses,parasitism, and parasite transmission by xenodiagnosis

Background

The incidence of zoonotic canine visceral leishmaniasis (CVL) would decrease if dogs were effectively vaccinated; however, additional data on the efficacy of canine vaccines are required for their approved preventative use.

Purpose

To prospectively evaluate vaccination outcomes using two products commercially available in Brazil, with respect to adverse reactions (reactogenicity), humoral response, disease signs, parasitism, and parasite infectiousness in naturally exposed pet dogs in an endemic area of visceral leishmaniasis (VL).

Methods

From 2010 to 2012, healthy dogs were vaccinated with Leishmune^® (50 animals) or Leish-Tec^® (50 animals). Each dog was examined to identify clinical signs during peri- and post-vaccination procedures every 2 months for 11 months to identify the presence of parasites or parasite DNA in splenic samples using culturing or PCR, respectively. Levels of anti-Leishmania IgG, IgG1, and IgG2 were quantified in sera by ELISA and infectiousness was assessed by xenodiagnosis.

Results

Adverse effects occurred in 2.2% (1/45) and 13.0% (6/46) of the animals in the Leishmune^® and Leish-Tec^® groups, respectively. IgG levels peaked on the 21st day following the first dose of Leishmune^® and on the 21st day after the second dose of Leish-Tec^®. The final seropositivity rate for IgG was 32.5% (13/40) and 30.9% (13/42) in the Leishmune^® and Leish-Tec^® groups, respectively. The Leishmune^® group presented higher levels of IgG1 and IgG2 compared to the Leish-Tec^® group (p < 0.001), and ELISA reactivity in both vaccinated groups was significantly lower (p < 0.001) than in infected positive control dogs. Parasitism was observed in 12.2% (5/41) of the Leishmune^® group, and 7.9% (3/38) of the Leish-Tec^® group, with xenodiagnostic transmission rates of Leishmania to Lutzomyia longipalpis of 5.1% (2/39), and 5.4% (2/37), respectively.

Conclusions

No significant differences were observed in dogs vaccinated with Leishmune^® or Leish-Tec^®, with respect to LVC clinical aspects, parasitism, IgG seropositivity, or dog infectiousness. The Leishmune^®-vaccinated animals presented higher levels of IgG, IgG1, and IgG2. The animals vaccinated with Leish-Tec^® exhibited adverse reactions with greater frequency and severity.     

Blinded, controlled field trial of two commercially available Mycoplasma bovis bacterin vaccines in veal calves

Mycoplasma bovis is an etiologic agent of pneumonia, arthritis, and otitis in young calves, such as those found in the special-fed veal industry. We conducted a blinded, controlled trial of two commercially available M. bovis bacterin vaccines for the prevention of respiratory disease in calves associated with M. bovis infection. Calves were randomly assigned to a subcutaneous treatment of vaccine A (n = 50), adjuvant A (n = 50), vaccine B (n = 50), or 0.9% sterile saline solution (n = 50) beginning at 27 days of age. Upper-respiratory tract colonization was not impacted by vaccination status. Vaccine A significantly reduced the presence of lung lesions (p = 0.0325), however there was no significant reduction of M. bovis in lung lesions. Vaccine B did not significantly reduce total lung lesions or M. bovis-specific lung lesions. The relative risk was determined to be 0.56, 1.0, and 1.36 for vaccine A, adjuvant A, and vaccine B, respectively. There was no association between the total specific antibody isotype (IgM, IgG1, IgG2, IgA) concentrations or M. bovis antibodies and the M. bovis-associated morbidity in the veal calves. Under the field conditions of this study, observed vaccine efficacy for vaccine A and vaccine B was 44% and less than 1%, respectively.     

Safety and immunogenicity of SC599, an oral live attenuated Shigella dysenteriae type-1 vaccine in healthy volunteers: Results of a Phase 2, randomized,double-blind placebo-controlled trial

SC599 vaccine is a live Shigella dysenteriae 1 strain attenuated by deletion of invasion [icsA], iron chelation [ent, fep] and shiga toxin A subunit [stxA] genes. In a preliminary Phase 1 single dose prospective study, we showed that SC599 vaccine was well tolerated, and the maximum tolerable dose was greater than 10⁸ CFU [Sadorge C, Ndiaye A, Beveridge N, Frazer S, Giemza R, Jolly N, et al. Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 ΔicsA Δent Δfep ΔstxA:HgR oral vaccine SC599 in healthy human adult volunteers. Vaccine 2008; 26(7):978–8]. In this Phase 2 trial, three groups of volunteers ingested a single dose of SC599 [10⁵ CFU, n = 38; 10⁷ CFU, n = 36] or placebo [n = 37]. Both 10⁵ and 10⁷ CFU doses were immunogenic, inducing significant IgA and IgG LPS-specific ASCs and antibody responses, comparable in magnitude to those of other strains that prevented illness following experimental challenge. In the intention to treat analysis, 34.2% and 44.4% IgA ASC responders were detected in the 10⁵ and 10⁷ CFU groups respectively (p < 0001 vs placebo for both groups), as well as 31.6% and 33.3% serum IgA responders (p < 001 and p < 0.001 vs placebo for 10⁵ and 10⁷ CFU groups, respectively). No difference between the two vaccine groups was observed. No stxB-specific antibody response was detected in the vaccines. SC599 excretion occurred in 23.7 and 30.6% of subjects in the 10⁵ and 10⁷ CFU groups, respectively. SC599 vaccine was well tolerated, and the reported adverse events were mainly digestive. These results indicate that a single oral immunization of SC599 vaccine elicits a significant circulating IgA ASC and serum antibody response that may confer protection against the most severe symptoms of Shigellosis in responders to the vaccine.     

Humoral immune response to oral rabies vaccination in raccoon kits: Problems and implications

Little is known about the immunogenicity of RABORAL V-RG^® (V-RG), an oral rabies vaccine, in raccoon kits (Procyon lotor). The objectives of this study were to characterize the immunogenicity of V-RG in young kits and investigate the potential impact of maternal antibodies on response to vaccination of nursing raccoon kits. Raccoon kits (n = 30) were vaccinated at either 3 weeks of age, 7 weeks of age, or assigned as contact controls. Nineteen kits (73%) that were whelped by unvaccinated mothers responded to V-RG exposure (orally or indirect contact) by production of detectable rabies virus neutralizing antibodies (RVNA) while 7 (27%) kits did not respond to V-RG exposure. Four kits were whelped by a mother with high levels of RVNA and all four kits acquired maternal rabies antibodies. At approximately 9 months of age, all kits were inoculated with a killed rabies vaccine, IMRAB3^®. The kits which initially responded to V-RG oral vaccination or contact with vaccinated littermates demonstrated a rapid anamnestic response. In contrast, the V-RG non-responders and those with acquired maternal antibodies exhibited a primary immune response to IMRAB3^®, where RVNA levels were substantially lower on days 5 and 7 than the levels in the animals with an anamnestic response. These findings suggest that the naïve contact kits and the nonresponsive kits most likely remained susceptible to rabies virus infection whereas the ones demonstrating response to V-RG would not have been susceptible to a rabies virus infection.