Skills (5)
Publications (11) View all
-
Article: Construction and characterization of human rotavirus recombinant VP8* subunit parenteral vaccine candidates.
[show abstract] [hide abstract]
ABSTRACT: Two currently licensed live oral rotavirus vaccines (Rotarix(®) and RotaTeq(®)) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in Escherichia coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines.Vaccine 08/2012; 30(43):6121-6. · 3.77 Impact Factor -
Article: The VP7 genes of two G9 rotaviruses isolated in 1980 from diarrheal stool samples collected in Washington, DC, are unique molecularly and serotypically.
[show abstract] [hide abstract]
ABSTRACT: In a retrospective study of archival diarrheal stool samples collected from 1974 to 1991 at Children's Hospital National Medical Center, Washington, DC, we detected three genotype G9P[8] viruses in specimens collected in 1980, which represented the earliest human G9 viruses ever isolated. The VP7 genes of two culture-adapted 1980 G9 viruses were phylogenetically related closely to the lineage 2 G9 virus VP7 gene. Unexpectedly, however, the VP7s of the 1980 G9 viruses were more closely related serotypically to lineage 3 VP7s than to lineage 2 VP7, which may be supported by amino acid sequence analyses of the VP7 proteins.Journal of Virology 05/2008; 82(8):4175-9. · 5.40 Impact Factor -
Article: A rotavirus strain isolated from pig-tailed macaque (Macaca nemestrina) with diarrhea bears a P6[1]:G8 specificity.
[show abstract] [hide abstract]
ABSTRACT: A distinct rotavirus strain (PTRV) was isolated in cell cultures from a stool sample obtained from a diarrheic 3-year-old female pig-tailed macaque (Macaca nemestrina) that was born at the breeding colony of the University of Washington in Seattle. Unlike other known simian rotavirus strains including vervet monkey rotavirus SA11 which bears P5B[2]:G3 or P6[1]:G3 specificity, rhesus monkey rotavirus MMU18006 with P5B[3]:G3 specificity, pig-tailed macaque rotavirus YK-1 with P[3]:G3 specificity and rhesus monkey rotavirus TUCH with P[24]:G3 specificity, the cell-culture-grown PTRV strain was shown to bear P6[1]:G8 specificity as determined by VP4 (P)- and VP7 (G)-specific neutralization assays as well as gene sequence analyses. The virus in the original diarrhea stool was also shown to bear genotypes P[1] and G8. In addition, the PTRV strain exhibited a "long" electropherotype, subgroup I specificity and NSP4 genotype A specificity. The PTRV probe formed (i) 8-9 hybrid bands with genomic RNAs of various bovine rotavirus strains and (ii) only 2-3 hybrid bands with simian rotavirus RNAs as demonstrated by RNA-RNA hybridization, suggesting a possible bovine origin of the virus. Serologic analysis of serum samples obtained from selected pig-tailed macaques in the colony suggested that a rotavirus bearing P[1]:G8 specificity was endemic among macaques for at least 8 years (1987-1994). This is the first report describing an isolation of a simian rotavirus bearing a non-G3 VP7 and possibly a P6[1] specificities. Because of its unique simian serotype, this virus may prove to be valuable in challenge studies in a non-human primate model in studies of rotavirus immunity.Virology 03/2006; 345(1):1-12. · 3.35 Impact Factor -
Article: Porcine rotavirus strain Gottfried-based human rotavirus candidate vaccines: construction and characterization.
[show abstract] [hide abstract]
ABSTRACT: Rotavirus gastroenteritis remains the leading cause of severe diarrheal disease in infants and young children worldwide, and thus, a safe and effective rotavirus vaccine is urgently needed in both developing and developed countries. Various candidate rotavirus vaccines that were developed by us and others have been or are being evaluated in different populations in various parts of the world. We have recently confirmed that a porcine rotavirus Gottfried strain bears a P (VP4) serotype (P2B[6]) closely related to human rotavirus P serotype 2A[6] which is of epidemiologic importance in some regions of the world. Based on the modified Jennerian approach to immunization, we have constructed 11 Gottfried-based single VP7 or VP4 gene substitution reassortant vaccine candidates which could provide: (i) an attenuation phenotype of a porcine rotavirus in humans; and (ii) antigenic coverage for G serotypes 1-6 and 8-10 and P serotype 1A[8], 1B[4] and 2A[6]. In addition, following immunization of guinea pigs with Gottfried VP4, we found low but consistent levels of neutralizing antibodies to VP4 with P1A[8] or P1B[4] specificity, both of which are of global epidemiologic importance. Thus, porcine-based VP7 reassortant rotavirus vaccines may provide an advantage over rhesus- or bovine-based VP7 reassortant vaccines since the VP4s of the latter vaccines do not evoke antibodies capable of neutralizing the viruses bearing P1A[8], P1B[4] or P2A[6] VP4.Vaccine 06/2005; 23(29):3791-9. · 3.77 Impact Factor -
Article: A porcine G9 rotavirus strain shares neutralization and VP7 phylogenetic sequence lineage 3 characteristics with contemporary human G9 rotavirus strains.
[show abstract] [hide abstract]
ABSTRACT: Of five globally important VP7 (G) serotypes (G1-4 and 9) of group A rotaviruses (the single most important etiologic agents of infantile diarrhea worldwide), G9 continues to attract considerable attention because of its unique natural history. Serotype G9 rotavirus was isolated from a child with diarrhea first in the United States in 1983 and subsequently in Japan in 1985. Curiously, soon after their detection, G9 rotaviruses were not detected for about a decade in both countries and then reemerged in both countries in the mid-1990s. Unexpectedly, however, such reemerged G9 strains were distinct genetically and molecularly from those isolated in the 1980s. Thus, the origin of the reemerged G9 viruses remains an enigma. Sequence analysis has demonstrated that the G9 rotavirus VP7 gene belongs to one of at least three phylogenetic lineages: lineage 1 (strains isolated in the 1980s in the United States and Japan), lineage 2 (strains first isolated in 1986 and exclusively in India thus far), and lineage 3 (strains that emerged/reemerged in the mid-1990s). Currently, lineage 3 G9 viruses are the most frequently detected G9 strains globally. We characterized a porcine rotavirus (A2 strain) isolated in the United States that was known to belong to the P[7] genotype but had not been serotyped by neutralization. The A2 strain was found to bear serotype G9 and P9 specificities as well as NSP4 [B] and subgroup I characteristics. By VP7-specific neutralization, the porcine G9 strain was more closely related to lineage 3 viruses than to lineage 1 or 2 viruses. Furthermore, by sequence analysis, the A2 VP7 was shown to belong to lineage 3 G9. These findings raise intriguing questions regarding possible explanations for the emergence of variations among the G9 strains.Virology 03/2005; 332(1):177-88. · 3.35 Impact Factor
