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C Barone

Publications and source records attributed to C Barone.

At least 19 recordsLinked to original sources
PubMed2004

Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study.

BACKGROUND: Cisplatin, paclitaxel and 5-fluorouracil (5-FU) have demonstrated significant activity in patients with advanced squamous head and neck cancer (HNSCC) despite relevant toxicity. A weekly administration of cisplatin and paclitaxel with continuous infusion of 5-FU could offer a better toxicity profile without affecting dose intensity or treatment outcome. We evaluated the toxicity and the activity of weekly cisplatin/paclitaxel with continuous infusion 5-FU in patients with recurrent and/or metastatic HNSCC. METHODS: A total of 44 patients were studied. Treatment consisted of two 6-week cycles with weekly cisplatin 20 mg/m2 and paclitaxel 60 mg/m2 and daily continuous infusion 5-FU 200 mg/m2 from day 1 to 42. Patients were evaluated for toxicity and response. RESULTS: 40 out of 44 patients were evaluable for response. After two cycles we observed seven complete responses (16%) and 12 partial responses (27%), with a 43% (95% CI 28-58%) overall response rate. Stable disease was seen in 13 patients (29%) and progressive disease in 12 patients (27%). Toxicity was mild in treated patients: we observed less than 10% of grade 3/4 hematological and gastroenteric toxicity. CONCLUSIONS: A weekly schedule of cisplatin and paclitaxel associated with continuous infusion 5-FU showed low toxicity in the treatment of advanced HNSCC while significant activity was conserved.

Adult↗
PubMed2004

Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients.

BACKGROUND: The aim of this study was to observe the effects of neoadjuvant therapy with irinotecan and 5-fluorouracil (5-FU)/folinic acid (FA) on the resection rate and survival of colorectal cancer patients with initially unresectable hepatic metastases. PATIENTS AND METHODS: Forty patients received neoadjuvant chemotherapy comprising irinotecan 180 mg/m(2) administered intravenously (i.v.) on day 1, FA 200 mg/m(2) i.v. on days 1 and 2, 5-FU 400 mg/m(2) i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m(2) as a continuous 48-h i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was assessed every 12 weeks (six cycles). RESULTS: The objective response rate to chemotherapy was 47.5% (n = 19), with two complete responses and disease stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients undergoing surgery within 2 weeks. Treatment was well tolerated and adverse events were typical of the chemotherapy agents used. Twenty-seven (67.5%) patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%) reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%) underwent potentially curative liver resection following chemotherapy. Chemotherapy was particularly effective in patients with large metastases on entry to the study. The median time to progression is 14.3 months and, at a median follow-up of 19 months, all patients are alive. CONCLUSIONS: Neoadjuvant therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. The effects of treatment on survival have yet to be determined.

Adult↗
PubMed2004

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study.

BACKGROUND: To identify the most effective of two combinations, irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) and irinotecan/cisplatin, in the treatment of advanced gastric cancer, for investigation in a phase III trial. PATIENTS AND METHODS: Patients were randomized to receive irinotecan [80 mg/m2 intravenously (i.v.)], FA (500 mg/m2 i.v.) and a 22-h infusion of 5-FU (2000 mg/m2 i.v.), weekly for 6 weeks with a 1-week rest, or irinotecan (200 mg/m2 i.v.) and cisplatin (60 mg/m2 i.v.), on day 1 for 3 weeks. RESULTS: A total of 115 patients were eligible for analysis in the per-protocol population. The overall response rate in the irinotecan/5-FU/FA arm (n=59) was 42.4%, with a complete response rate of 5.1%. Corresponding figures for the irinotecan/cisplatin arm (n=56) were 32.1% and 1.8%, respectively. The median time to progression was 6.5 months (irinotecan/5-FU/FA) and 4.2 months (irinotecan/cisplatin) (P < 0.0001), with median survival times of 10.7 and 6.9 months, respectively (P=0.0018). The major toxicity was grade 3/4 neutropenia, which was more pronounced with irinotecan/cisplatin than with irinotecan/5-FU/FA (65.7% versus 27%). Diarrhea was the main grade 3/4 non-hematological toxicity with both irinotecan/5-FU/FA (27.0%) and irinotecan/cisplatin (18.1%). CONCLUSIONS: Both combinations were active, with acceptable safety profiles. Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer.

Adenocarcinoma↗
PubMed2004

Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin, etoposide and cisplatin in gastric cancer.

OBJECTIVE: The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both resectability and survival. Here, we report the results of the long-term follow-up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of patients carefully staged by computed tomography (CT), endoscopic ultrasound and laparoscopy. METHODS: Twenty-five stage II-III patients with histologically proven gastric adenocarcinoma were enrolled in the study. All patients gave informed consent and were thoroughly staged. Patients were treated with epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre-operative cycles before CT clinical restaging followed by laparotomy and D2 gastrectomy. Three further cycles of chemotherapy were planned after radical surgery. RESULTS: Twenty-four patients received the planned pre-operative chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7 patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a result of gastric bleeding. Perioperative complications occurred in 5 patients (failure of anastomosis in 1 patient and wound infection in the other 4). The pathologic response rate included 7 partial responses (29.1%) and 10 patients with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%), which occurred more frequently during the postoperative chemotherapy, and fatigue (68%). Fever or infection, however, were never observed. The median disease-free survival was 37 months, and median survival has not been reached after 40 months of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%, respectively. CONCLUSION: The notable long-term survival in the present study suggests a comparison between the neoadjuvant approach, including new drug combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced gastric cancer.

Adenocarcinoma↗
PubMed2004

Isolated splenic metastasis from colon cancer.

Solid-tumor metastases of the spleen are rare and usually associated with disseminated disease. There are only seven reports in literature of isolated splenic metastases from colorectal carcinoma, which generally metastasize to regional lymphonodes, liver and abdominal peritoneum. We report a case of isolated splenic metastasis in a 55-year-old woman who had undergone left hemicolectomy, lymphadenectomy and chemotherapy 18 months earlier for adenocarcinoma of the sigmoid colon with positive pericolic and inter-aortocaval lymphonodes. This is the eighth documented case of isolated splenic metastasis from colon cancer. Previously reported cases of this type are reviewed along with the mechanism underlying neoplastic spread to the spleen.

Adenocarcinoma↗
PubMed2003

Weekly gemcitabine and 24-hour infusional 5-fluorouracil in advanced pancreatic cancer: a phase I-II study.

OBJECTIVE: In this phase I-II study we explored the potential of the combination of weekly gemcitabine (GEM) and 24-hour continuous infusion of 5-fluorouracil (5-FU) in order to determine the toxicity profile in pancreatic cancer. The efficacy of this drug combination was studied as a secondary endpoint. METHODS: Twenty-one patients with histologically or cytologically proven unresectable or metastatic previously untreated pancreatic adenocarcinoma were included in this study. Two dose levels of GEM and two dose levels of 5-FU were evaluated in three cohorts of patients who received GEM 1,000 mg/m(2) and 5-FU 2,000 mg/m(2), GEM 1,200 mg/m(2) and 5-FU 2,000 mg/m(2), or GEM 1,200 mg/m(2) and 5-FU 2,250 mg/m(2), on days 1, 8, and 15, every 4 weeks, respectively. RESULTS: Grade 3-4 neutropenia was observed in 10% of the cycles. Non-myelosuppressive toxicities included fatigue (22%), grade 1-2 diarrhea (12%) and grade 1 liver toxicity. There was no limiting toxicity and the maximum tolerated dose has not been reached. Two patients experienced a partial response (9.5 +/- 12.6%) and 12 patients had stable disease (57.1 +/- 21.2%). Seven of the 14 symptomatic patients improved their disease-related symptoms and 4 of the 8 patients evaluable for clinical benefit had a clinically beneficial response (50 +/- 34.6%). The median progression-free survival was 6 months (range 2-28), median survival was 11 months (range 3-32+), and the actuarial 1-year survival rate 33%. CONCLUSION: The weekly administration of GEM combined with 24-hour continuous infusion of 5-FU shows a good safety profile at the dose levels evaluated. Some partial responses had also been achieved, disregarding the dose level of the two drugs. Survival confirms the activity of this drug combination.

Adult↗
PubMed2002

Duplex scanning of neck vessels: need for extending the consensus on indications.

We studied the percentage and distribution of appropriate indications for duplex scanning of neck vessels in an outpatient population. A total of 650 consecutive outpatients sent by their general practitioner (GP) or a specialist for duplex scanning of epi-aortic arterial vessels were studied. The aim was to verify the percentage of appropriate (APR) an inappropriate (INAPR) indications for the examination, according to the current literature. After analysis of indications as reported by GPs or specialists and a brief anamnestic examination, 77% of patients were found to have had one or more APR and 23% of patients had none. Analysis of severity of atheromasic lesions between the two groups showed that patients with APR had significantly ( p<0.001, chi-square test) more severe lesions than patients with INAPR. In more detail, no patient with INAPR had severe (>60%) stenosis while 6.4% of patients with APR had severe stenosis. Moreover, the percentage of normal examinations or intima-media thickness only was 32.5% in patients with INAPR but fell to 17.2% in patients with APR. In the entire group, women were more represented than men even after consideration of the natural prevalence of female gender in the local population. Among inappropriate indications for the examination, isolated dizziness or vertigo, syncope and tinnitus were the most frequent. Continuous medical education is needed to reduce inappropriate indications and thus to find solutions, although partial, to shorten the waiting lists that have become an urgent problem for the public health systems of several Western countries. However, this appears to be difficult challenge, as experiments conducted on this issue by other researchers only gave transient positive results.

Aged↗
PubMed2002

Predictive value of thymidylate synthase expression in resected metastases of colorectal cancer.

Recent investigations have focused on the prognostic value of thymidylate synthase (TS) assessment in metastases of colorectal carcinoma (CRC). In order to evaluate the prognostic impact of TS expression after resection of metastases of colorectal cancer followed by systemic adjuvant chemotherapy, we performed an immunohistochemical characterisation of TS in the primary tumours and in the corresponding radically resected hepatic and pulmonary metastases. An additional objective was to compare the levels of TS in primary and metastatic disease. TS expression was assessed by immunohistochemistry using the monoclonal antibody TS 106. The study population consisted of 60 patients: 48 underwent liver and 12 lung resection. All of them received adjuvant chemotherapy after metastasectomy according to the Mayo Clinic schedule. In the 49 evaluable primary tumours, TS score was high in 53% and low in 47% of patients, while in the 60 metastatic samples TS immunostaining was high in 33% and low in 67%. There was a significantly smaller number of high TS expressors in metastatic than in primary tumours (P<0.04). No correlation was observed between TS expression and the site of the metastasis. TS status did not significantly correlate with the median disease-free interval (DFI) after metastasectomy, although this parameter was longer for patients with low TS immunoreactivity in the resected metastases than for those with high TS lesions (19.6 versus 13.8 months). Patients with high TS levels, however, had a significantly shorter median overall survival (OS) (27.6 months) than those with low TS expression (36.3 months) (P<0.008). TS status in the resected metastases confirmed its independent prognostic value in the multivariate analysis and was the only prognostic marker of OS in the subgroup of patients with resected liver metastases. These results suggest that high TS levels in resected metastases of colorectal cancer are associated with a poor outcome after surgery and 5-FU adjuvant therapy; therefore, a prospective assessment of TS levels in resected colorectal metastases could be useful to define which patients will most likely benefit from 5-FU adjuvant therapy after metastasectomy. Chemotherapeutic agents that target TS may not be the appropriate adjuvant treatment after metastasectomy for patients with a high TS expression in the resected metastases of colorectal cancer.

Adult↗
PubMed2001

Allele varepsilon4 of apolipoprotein E gene is less frequent in Down syndrome patient of the Sicilian population and has no influence on the grade of mental retardation.

We evaluated the allele (and genotype frequencies in 60 Down syndrome (DS), 25 mothers and 57 controls from Sicily and its relation with mental retardation. DS patients and sex ratio (M:F) was 22.1+/-10.5 and 1.14, respectively. Allele varepsilon4 and varepsilon3 frequencies were respectively lower (P=0.015) and higher (P=0.005) in DS patients compared to controls. Genotype varepsilon3/varepsilon4 and varepsilon3/varepsilon3 were less (P=0.03) and more frequent (P=0.001) in DS patients, with respective odd ratios of 0.31 (CI at 95%: 0.18-0.49) and of 4.4 (CI at 95%: 3.4-5.7). No difference of allele (distribution was found in function of the grades of mental retardation according to DMS-IV. Our results show that the implication of Apo-E4 in the pathogenesis of Alzheimer disease cannot be extrapolated in that of dementia of DS.

Adolescent↗
PubMed2000

Evidence of cerebral hypoperfusion in scleroderma patients.

OBJECTIVES: To investigate regional cerebral blood flow by (99m)Tc-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT) in a series of 40 patients (mean age 58.5+/-11.5 yr) affected by systemic sclerosis (SSc) in comparison with age-matched healthy controls. METHODS: Subjects affected by concomitant severe pathologies that might interfere with the interpretation of the SPECT results were excluded. SPECT findings were correlated with the severity of peripheral microvascular involvement, as assessed by nailfold videocapillaroscopy (NVC). Whenever possible, patients underwent magnetic resonance imaging (MRI) of the brain. RESULTS: Twenty-one SSc patients (52%) showed hypoperfusion in two or more regions of interest (ROIs) at the SPECT analysis. MRI was available in 14 of these patients, and was shown to be altered in eight of them (57%). One patient with both abnormal SPECT and abnormal MRI was affected by mild cognitive impairment. Transcranial Doppler sonography was normal in all but one of these patients with hypoperfusion. Nineteen patients exhibited a normal brain SPECT scan, but the MRI was shown to be altered in 3/12 of them (25%). No significant differences were found between the group of SSc patients showing hypoperfusion and those showing a normal SPECT scan regarding age, the duration of disease, the presence of vascular risk factors or damage of other organs typically involved in the disease, and the severity of peripheral microvascular involvement (NVC). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion was found in more than half of the neurologically asymptomatic SSc patients studied, paralleling the incidence of altered brain MRI. The hypoperfusion was not linked to ageing and possibly reflects the cerebral location of the microangiopathic process characterizing the disease.

Adult↗
PubMed2000

Use of drug effect interaction modeling with Monte Carlo simulation to examine the impact of dosing interval on the projected antiviral activity of the combination of abacavir and amprenavir.

The delineation of optimal regimens for combinations of agents is a difficult problem, in part because, to address it, one needs to (i) have effect relationships between the pathogen in question and the drugs in the combination, (ii) have knowledge of how the drugs interact (synergy, antagonism, and additivity), and (iii) address the issue of true between-patient variability in pharmacokinetics for the drugs in the population. We have developed an approach which employs a fully parametric assessment of drug interaction using the equation of W. R. Greco, G. Bravo, and J. C. Parsons (Pharmacol. Rev. 47:331-385, 1995) to generate an estimate of effects for the two drugs and have linked this approach to a population simulator, using Monte Carlo methods, which produce concentration-time profiles for the drugs in combination. This software automatically integrates the effect over a steady-state dosing interval and produces an estimate of the mean effect over a steady-state interval for each simulated subject. In this way, doses and schedules can be easily evaluated. This software allows for a rational choice of dose and schedule for evaluation in clinical trials. We evaluated different schedules of administration for the combination of the nucleoside analogue abacavir plus the human immunodeficiency virus type 1 protease inhibitor amprenavir. Amprenavir was simulated as either 800 mg every 8 h (q8h) or 1,200 mg q12h, each along with 300 mg q12h of abacavir. Both regimens produced excellent effects over the simulated population of 500 subjects, with average percentages of maximal effect (as determined from the in vitro assays) of 90.9%+/- 11.4% and 80.9%+/-18.6%, respectively. This difference is statistically significant (P<<0.001). In addition, 68.8 and 46.0% of the population had an average percentage of maximal effect which was greater than or equal to 90% for the two regimens. We can conclude that the combination of abacavir plus amprenavir is a potent combination when it is given on either schedule. However, the more fractionated schedule for the protease inhibitor produced significantly better effects in combination. Clinicians need to explicitly balance the improvement in antiviral effect seen with the more fractionated regimen against the loss of compliance attendant to the use of such a regimen. This approach may be helpful in the preclinical evaluation of multidrug anti-infective regimens.

Anti-HIV Agents↗
PubMed2000

Vinorelbine and alternating cisplatin and ifosfamide in the treatment of non-small cell lung cancer.

In order to explore the activity of a combination of vinorelbine (VNL) and alternating cisplatin (CDDP) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), a phase II study was performed. Seventy chemoradiotherapy naive patients with NSCLC, stage IIIA, IIIB and IV disease, PS (ECOG) </=2, were treated with CDDP 40 mg/m(2) on days 1, 2, 3, IFX 1,800 mg/m(2) on days 22, 23, 24 and VNL 30 mg/m(2) on days 1, 8, 22, 29 every 6 weeks up to 6 courses. In the 67 evaluable patients, an objective response rate was observed in 47.8 +/- 12% (95% CI) with complete responses in 6%; responses occurred more frequently in patients with locally advanced disease (stage IIIA/IIIB) and/or performance status 0. The median duration of survival was 12 months: 19.9 months in stage III patients who received an integrated treatment and 10 months in metastatic disease. The median time to treatment failure was 10.5 months. Toxicity was mainly hematological, even though it was not dose-limiting and easily manageable. This combination seems to be active, and the good safety profile is probably the result of the use of an alternating schedule of CDDP and IFX. Median overall survival was also encouraging in stage IV disease. The prolongation of survival obtained when surgery and/or radiotherapy is applicable needs confirmation through a larger study.

Adult↗
PubMed2000

Comparison of three probiotics in the treatment of acute diarrhea in mentally retarded children.

BACKGROUND: This article aims to compare the use of VIS-01 (Yovis) with two other probiotics (lactic acid bacteria), such as Lactogèrmine and Codex in the treatment of acute diarrhea in children with mental retardation. A recent paper highlights the superiority of the first drug, claiming new perspectives in probiotic therapy. METHODS: The authors perform a prospective study on 33 mentally retarded children (mean age 10.3 years), divided in three groups, each treated with a different probiotic (VIS-01, Lactogèrmine and Codex) at the beginning of an acute diarrhea. These children were admitted at the Pediatric Unit of the Oasi Maria SS. Institute in Troina. The dosage was suited to the technical record of the drug. During the clinical course the following items have been recorded: number of evacuations; time of alvine normalization; presence, quality, and length of fever; other associated features or side effects. RESULTS: The time of alvine normalization did not show statistically significant differences between the three groups. CONCLUSIONS: In conclusion, the use of Yovis does not modify in a statistically significant way with respect to the remaining drugs the clinical course of acute diarrhea in the mentally retarded children of the present study.

Child↗
PubMed1999

Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles.

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine ECwt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.

Adjuvants, Immunologic↗
PubMed1999

A prevalence study of celiac disease in persons with Down syndrome residing in the United States of America.

In order to estimate the prevalence of celiac disease in persons with Down syndrome, 105 patients with this chromosomal disorder residing on the East Coast of the United States of America were enrolled in this study. IgA and IgG antigliadin antibodies (AGA) were determined using a fluorescent immunoenzymatic assay, and antiendomysium antibodies (AEA) were measured with immunofluorescence on monkey oesophagus. Of the 105 patients, 5 were positive for AEA, 4 were positive for IgG AGA, and 1 was positive for IgG AGA and AEA. Of the five patients with high titres of AEA, four consented to a jejunal biopsy, which revealed significant villous atrophy. Thus, 4 (possibly 5) patients in this cohort of 105 individuals with Down syndrome have celiac disease.

Adolescent↗
PubMed1999

Heterotypic protection and induction of a broad heterotypic neutralization response by rotavirus-like particles.

The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11. Immunization with VLPs may provide sufficient priming of the immune system to induce protective anamnestic heterotypic neutralizing antibody responses upon subsequent rotavirus infection. Therefore, a limited number of serotypes of VLPs may be sufficient to provide a broadly protective subunit vaccine.

Animals↗
PubMed1998

Rotavirus disease, but not infection and development of intestinal histopathological lesions, is age restricted in rabbits.

The rabbit model of rotavirus infection has proved to be useful for assessing active immunity and protection after infection or vaccination with virus or virus-like particles. One limitation of the rabbit model is that after experimental infection of rabbits, clinical diarrhea is not routinely induced. Lack of diarrhea in the rabbit model has been proposed to be due to the fluid absorptive capability of the cecum or attenuation of virus strains through tissue culture adaptation. To test whether a wild-type lapine rotavirus strain BAP (BAPwt) isolated from diarrheic rabbits would cause disease on passage in rabbits, 1-, 2-, 10-, and 16-week-old rabbits were orally inoculated with BAPwt, its tissue culture-adapted counterpart strain (BAP-2), tissue culture-adapted lapine strain ALA, or PBS. Lapine rotavirus infection in 1-week-old, but not >/=2-week-old, rabbits resulted in the development of disease characterized by soft, wet, yellow-to-brownish-green partially formed-to-liquid stools observed only at the time of virus antigen shedding. The level and duration of virus shedding after infection were prolonged in 1-week-old rabbits compared with rabbits >/=2 weeks of age. Although diarrhea was not observed beyond the first 2 weeks of life, histopathological changes, including villus shortening and fusion, increased vacuolation of epithelial cells, and mononuclear infiltration of the lamina propria, were observed throughout the small intestine between 12 and 120 h after ALA infection in 1-week-old, 1- to 2-month-old, and 11-month-old rabbits. In 11-month-old rabbits, onset of intestinal damage appeared to be slightly delayed, was less severe, and was not observed in the duodenum. There were no differences in the immune responses to rotavirus infection in rabbits of different age groups (1 week to 5 years of age). All lapine rotavirus-inoculated rabbits seroconverted and were protected from virus challenge at 28 days postinoculation. Like in mice, rotavirus disease is age restricted in rabbits.

Aging↗