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Suzanne U Emerson

Publications and source records attributed to Suzanne U Emerson.

8 recordsLinked to original sources
PubMed2003

Pre-clinical immunogenicity and efficacy trial of a recombinant hepatitis E vaccine.

We have demonstrated that recombinant hepatitis E vaccine suitable for clinical evaluation was highly immunogenic and efficacious in preventing hepatitis E and even infection in rhesus macaques following intravenous challenge with three different genotypes of hepatitis E virus (HEV). Two doses of vaccine were essential for optimal protection; the two-dose regimen was more important than the formulation of the vaccine for achieving efficacy. The titers of anti-HEV that were protective in this study were quantified against a World Health Organization (WHO) standard. This permits direct comparison of the results with other studies. The results of this pre-clinical trial of a candidate hepatitis E vaccine strongly suggest that it will be highly efficacious for preventing hepatitis E in the field trial of this vaccine that is currently in progress in Nepal.

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PubMed2003

Importance of amino acid 216 in nonstructural protein 2B for replication of hepatitis A virus in cell culture and in vivo.

Clinical isolates of hepatitis A virus (HAV) replicate inefficiently in cell culture unless mutations are acquired throughout the genome. An Ala-to-Val substitution in the nonstructural protein 2B (2B-216) was known to have a major impact on replication in cell culture. Analysis of chimeric viruses confirmed that the 2B-A[216]V change was critical for efficient replication and that Leu or Ile could substitute for Val. Viruses containing Val, Ile, or Leu at 2B-216 all replicated with similar kinetics in cell culture, whereas the virus containing Ala at this position grew 10- to 20-fold less efficiently. In contrast, in vivo, virus with either Ala or Val at 2B-216 replicated equally efficiently when tested in a chimpanzee and in tamarins, and each amino acid was stably maintained. Attempts to complement wild-type 2B in trans with adapted 2B provided by co-infection with a second viable HAV mutant failed to enhance replication of the virus containing the wild-type 2B sequence.

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PubMed2002

Recombinant vaccine against hepatitis E: duration of protective immunity in rhesus macaques.

Hepatitis E virus (HEV) is an enterically transmitted virus that causes acute hepatitis. A candidate vaccine containing recombinant HEV capsid protein (56kDa) expressed in insect cells was shown previously to be highly immunogenic when administered in two doses to rhesus monkeys and to protect them from hepatitis E when challenged with a large intravenous dose of homologous or heterologous HEV. In the present study, the effect of a third dose of the same vaccine lot was evaluated and more importantly, the duration of protection following two doses was determined. Rhesus monkeys vaccinated twice with the 56kDa capsid protein were challenged with homologous virus 6 or 12 months after the last vaccination: 3 of 4 monkeys challenged 6 or 12 months later, respectively were protected against viral hepatitis. Similarly, all four of the rhesus monkeys given a third dose of vaccine 1 month prior to challenge were protected against hepatitis. In contrast, all four monkeys given placebo developed hepatitis following challenge. In summary, two doses of HEV vaccine partially protected rhesus monkeys from hepatitis E following intravenous challenge 6 or 12 months after vaccination.

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PubMed2002

Identification of VP1/2A and 2C as virulence genes of hepatitis A virus and demonstration of genetic instability of 2C.

Fourteen different chimeric virus genomes were constructed from two infectious cDNA clones encoding a virulent and an attenuated isolate, respectively, of the HM175 strain of hepatitis A virus. The ability of each recombinant virus to infect tamarins and to cause acute hepatitis was determined. Comparisons of the genotype and phenotype of each virus suggested that VP1/2A and 2C genes were responsible for virulence. The 2C gene derived from the attenuated parent virus was unstable, and one or more mutations arose in this gene during the first passage in tamarins.

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PubMed2001

Acute hepatitis caused by a novel strain of hepatitis E virus most closely related to United States strains.

A unique hepatitis E virus (HEV) strain was identified as the aetiological agent of acute hepatitis in a United States (US) patient who had recently returned from vacation in Thailand, a country in which HEV is endemic. Sequence comparison showed that this HEV strain was most similar, but not identical, to the swine and human HEV strains recovered in the US. Phylogenetic analysis revealed that this new HEV isolate was closer to genotype 3 strains than to the genotype 1 strains common in Asia. The fact that this HEV was closely related to strains recovered in countries where HEV is not endemic and was highly divergent from Asian HEV strains raises the questions of where the patient's infection was acquired and of whether strains are geographically as localized as once thought.

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PubMedDate not supplied

Hepatitis E virus.

Hepatitis E virus (HEV) is a positive-stranded RNA virus with a 7.2 kb genome that is capped and polyadenylated. The virus is currently unclassified: the organisation of the genome resembles that of the Caliciviridae but sequence analyses suggest it is more closely related to the Togaviridae. Hepatitis E virus is an enterically transmitted virus that causes both epidemics and sporadic cases of acute hepatitis in many countries of Asia and Africa but only rarely causes disease in more industrialised countries. Initially the virus was believed to have a limited geographical distribution. However, serological studies suggest that HEV may be endemic also in the United States and Europe even though it infrequently causes overt disease in these countries. Many different animal species worldwide recently have been shown to have antibodies to HEV suggesting that hepatitis E may be zoonotic. Although two related strains have been experimentally transmitted between species, direct transmission from an animal to a human has not been documented. There are four currently recognised genotypes and two of the four contain viruses isolated from swine as well as from humans. Regardless of country of origin or genotype of the virus, most, if not all, strains belong to a single serotype. A promising recombinant vaccine candidate comprised of a truncated capsid protein is currently under evaluation in Nepal.

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