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Synthetic peptides derived from bovine rotavirus C-486 (BRV) outer capsid (VP7 and VP4) and inner capsid (VP6) proteins were tested to evaluate their ability to prime and induce an anti-rotavirus antibody response. Peptides corresponding to the amino acid residues 232-255 of VP4 (VP4-peptide), 275-295 of VP7 (VP7-peptide) and 40-60 of VP6 (VP6-peptide) of BRV were chemically synthesized. These peptides...
A rhesus rotavirus vaccine adjuvanted with ISCOMs was injected intramuscularly to 5 pregnant baboons, with repeated doses 1-2 and 14 weeks after delivery. Maternal blood and milk samples and blood samples from their babies were collected at 2-weekly intervals until 26 weeks after parturition. Samples were assayed for rotavirus antibodies by ELISAs and neutralisation tests. Vaccination produced...
To examine the effect of MDP-Lys (L18), a derivative of muramyl dipeptide (MDP), as a mucosal immunoadjuvant, we investigated its activity to augment host resistance against mucosal infections by Sendai virus and rotavirus in mice. In an experimental infection model that suckling mice (10-day-old) were inoculated perorally (p.o.) with 1.5 10 6 p.f.u. mouse -1 of rotavirus...
Vaccines are commonly administered by the parenteral route. Therefore, adjuvant strategies which include parenteral immunization may improve the efficacy of a number of current vaccines. The capacity of aqueous-based microencapsulation to enhance virus-specific IgG responses in mice inoculated intramuscularly with small quantities of antigen was evaluated. Mice were inoculated with either 10 ...
Antibody responses and protection against shedding following oral challenge with murine rotavirus (EDIM) were determined in mice after sequential oral-parenteral immunization. Oral immunization of 4-day-old BALB/c mice with live, heterologous rotavirus (RRV) stimulated serum rotavirus IgG but little serum or intestinal rotavirus IgA and small but significant (P<0.001) reductions in EDIM shedding...
This study assessed the frequency of symptomatic and asymptomatic primary and secondary infections with rotavirus in children under 24 months and determined protection against symptomatic illness afforded by rhesus and human-rhesus rotavirus reassortant vaccines. Successive cohorts of children (n=236) were followed through five winter rotavirus seasons with cultures of each reported episode of diarrheal...
I.m. immunization of mice with inactivated rotavirus particles protects against subsequent infection. To optimize protection, the effects of different adjuvants (QS-21, QS-7, QUIL A, PCPP and RAS) with potential for human use were compared. Twenty-eight days after i.m. immunization with 20 μg of purified, UV/psoralen-inactivated murine rotavirus (EDIM), either with or without adjuvant, BALB/c mice...
The US just licensed of an oral tetravalent rhesus reassortant vaccine for routine immunization of infants against rotavirus. The virus was first identified 25 years ago and is now recognized to be the most common single cause of severe diarrhea throughout the world. Most children suffer at least one infection and reinfection is common. Studies of natural immunity show that breastfeeding may merely...
A parenterally administered rotavirus vaccine composed of virus-like particles (VLPs) is being evaluated for human use. VLPs composed of bovine VP6 and simian VP7 (SA11, G3) proteins (6/7-VLPs) or of bovine VP2, bovine VP6, and simian VP7 (SA11, G3) proteins (2/6/7-VLPs) were synthesized and purified from Sf9 insect cells co-infected with recombinant baculoviruses. 6/7- and 2/6/7-VLP administered...
The outer capsid protein of rotavirus, VP7, is a major neutralization antigen. A chimeric protein comprising Escherichia coli (E. coli) outer membrane protein A (OmpA) and part of porcine rotavirus VP7 containing all three antigenic regions (217 amino acids) was expressed in Salmonella and E. coli as an outer-membrane associated protein. Mice immunized intraperitoneally or orally, respectively, with...
We have previously shown that gene-gun delivery of murine rotavirus DNA vaccines to the epidermis induced protection against rotavirus challenge in mice. In this study, we used a rotavirus group antigen (VP6)-specific DNA vaccine to compare epidermal immunization with immunization to the anorectal epithelium for efficacy in inducing protective immunity. The vaccine was administered into cells of the...
This report describes the results of additional analyses of the trial carried out with the rhesus rotavirus-based quadrivalent vaccine in Venezuela. In the present study, we re-examined the data from this previous rotavirus vaccine trial to assess the statistical interaction between vaccine efficacy and (i) the duration of efficacy into the second year of life, (ii) socioeconomic conditions, and (iii)...
Intramuscular (i.m.) injection of murine VP6 DNA vaccines raised high titers of rotavirus-specific serum IgG and IgA antibodies in BALB/c mice. A Th1-like antibody response was generated based on the ratio of serum IgG2a to IgG1 antibodies. Rotavirus-specific serum IgA but not fecal IgA was detected in mice prior to rotavirus challenge. Partial protection against rotavirus challenge was achieved as...
Rotavirus specifically infects the small intestine of young infants resulting in severe diarrhoea. Mucosal antibody responses are required to cure the infection, and mucosal administration of rotavirus-like particles induces protective immunity without requiring a mucosal adjuvant such as cholera toxin. In addition, the rotavirus protein VP6 has been defined as a protective antigen in an adult mouse...
The undesirable side effects and variable efficacy of some oral live rotavirus vaccines in infants have necessitated alternative vaccine approaches. We evaluated a recombinant RFVP2/WaVP6 rotavirus-like-particle (2/6VLP) oral vaccine, using an immunostimulating complex (ISCOM) matrix as adjuvant, in a gnotobiotic (Gn) pig model of human rotavirus (HRV) disease. The 2/6VLPs adhered to the ISCOM-matrix...
Intranasal (i.n.) immunization of BALB/c mice with chimeric murine rotavirus EDIM (epizootic diarrhea of infant mice) VP6 and attenuated E. coli heat-labile toxin (LT), LT(R192G), stimulated >99% protection against rotavirus shedding after EDIM challenge. Here, we evaluated other potential adjuvants with chimeric VP6 administered by two mucosal routes: i.n. and oral. Besides LT(R192G), the adjuvants...
Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2 d ) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to...
The immunogenicity and protective efficacy of inactivated rotavirus vaccine administered intramuscularly with lipid adjuvants; MPL ( R) (monophosphoryl lipid A from Salmonella minnesota) or L3 ( R) (monooleate/lauric acid) was evaluated in an infant mouse model. Purified and formalin-inactivated rhesus rotavirus (I-RRV) combined with one of the adjuvants were administered to female...
We recently used ''functional mapping'' to locate protective epitopes in the carboxyl terminus (aa 197-397) of the VP6 protein (designated CD) of the EDIM strain of murine rotavirus [J. Virol. 74 (2000) 11574]. For this, H-2 d BALB/c mice were given two intranasal (i.n.) immunizations (separated by 2 weeks) with VP6 or CD genetically-fused to maltose-binding protein, or with overlapping synthetic...
We evaluated antibody responses and protection induced by attenuated Wa human rotavirus (AttHRV) and VP2/6-rotavirus-like particles (VLP), 100 or 250μg/dose, with immunostimulating complexes (ISCOM) (VLP/ISCOM) each given orally, alone or sequentially to gnotobiotic pigs. The AttHRV-VLP 250μg/ISCOM and three-dose-AttHRV (AttHRV3x) groups had significantly higher serum IgA, IgG and intestinal IgA antibody...
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