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Researchers from the United States and Turkey publish new studies and findings in the area of virology
[June 01, 2006]

Researchers from the United States and Turkey publish new studies and findings in the area of virology

(Science Letter Via Thomson Dialog NewsEdge)
New findings from the United States and Turkey describe advances in virology.

Study 1: Vaccination with chimeric SIN/VEE viruses cleared Venezuelan equine encephalitis virus from the brains of animals.

Scientists writing in the Journal of Virology report, "Venezuelan equine encephalitis virus (VFEV) is an important, naturally emerging zoonotic pathogen. Recent outbreaks in Venezuela and Colombia in 1995, involving an estimated 100,000 human cases, indicate that VEEV still poses a serious public health threat. To develop a safe, efficient vaccine that protects against disease resulting from VEEV infection, we generated chimeric Sindbis (SIN) viruses expressing structural proteins of different strains of VEEV and analyzed their replication in vitro and in vivo, as well as the characteristics of the induced immune responses."

"None of the chimeric SIN/VEE viruses caused any detectable disease in adult mice after either intracerebral (i.c.) or subcutaneous (s.c.) inoculation, and all chimeras were more attenuated than the vaccine strain, VEEV TC83, in six-day-old mice after i.c. infection," said Slobodan Paessler and colleagues at the University of Texas Medical Branch in Galveston. "All vaccinated mice were protected against lethal encephalitis following i.c., s.c., or intranasal (i.n.) challenge with the virulent VEEV ZPC738 strain (ZPC738)."

The scientists noted, "In spite of the absence of clinical encephalitis in vaccinated mice challenged with ZPC738 via i.n. or i.c. route, we regularly detected high levels of infectious challenge virus in the central nervous system (CNS). However, infectious virus was undetectable in the brains of all immunized animals at 28 days after challenge. Hamsters vaccinated with chimeric SIN/VEE viruses were also protected against s.c. challenge with ZPC738."

Paessler and associates concluded, "Taken together, our findings suggest that these chimeric SIN/VEE viruses are safe and efficacious in adult mice and hamsters and are potentially useful as VEEV vaccines. In addition, immunized animals provide a useful model for studying the mechanisms of the anti-VEEV neuro-inflammatory response, leading to the reduction of viral titers in the CNS and survival of animals."

Paessler and coauthors published their study in the Journal of Virology (Replication and clearance of Venezuelan equine encephalitis virus from the brains of animals vaccinated with chimeric SIN/VEE viruses. J Virol, 2006;80(6):2784-2796).

Additional information can be obtained by contacting Slobodan Paessler, Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019, USA.

Study 2: Scientists have determined the genetic stabilities of chimeric dengue vaccine candidates based on dengue 2 PDK-53 virus by sequencing and quantitative TaqMAMA.

Investigators in the United States report, "The genetic stabilities of the three attenuation loci of the candidate dengue 2 (D2) PDK-53 vaccine virus were evaluated for the PDK-53 virus and PDK-53-vectored chimeric D2/1 D2/3, and D2/4 viruses following 10 sequential passages in Vero cells. Sequencing revealed that the dominant NS1-53-Asp and the NS3-250-Val attenuation loci were extremely stable, whereas reversion occurred at the 5'NCR-57-U locus in 10 of the 18 viral lineages tested."

"A more sensitive and quantitative assay, the TaqMan mismatch amplification mutation assay (TaqMAMA), was employed to more finely discriminate the level of reversion at the 5'NCR-57 locus," said Siritorn Butrapet and colleagues at the U.S. Centers for Disease Control and Prevention. "This rapid genetic assay permitted detection of & le;1% reversion of YNCR-57 U-to-C in viral populations. By TaqMAMA, various levels of reversion at 5'NCR-57 were detected in all 18 of the PDK-53-based viral lineages tested at Vero passage 10, but only 3 lineages had reversion levels >80% in the viral population."

The researchers concluded, "Chimeric viruses based on the PDK-53-V (all three mutations present) genetic background were more stable than those developed in the PDK-53-E (5'NCR and NS1 mutations present) background. The TaqMAMA can be applied in quality control analyses to ensure that attenuated vaccine seeds contain undetectable or minimal levels of reversion at a given attenuation locus."

Butrapet and associates published their study in the Journal of Virological Methods (Determining genetic stabilities of chimeric dengue vaccine candidates based on dengue 2 PDK-53 virus by sequencing and quantitative TaqMAMA. J Virol Methods, 2006;131(1):1-9).

For additional information, contact Claire Y.-H. Huang, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 2087, Fort Collins, CO 80522, USA.

Study 3: Maternally derived hepatitis A virus antibodies decline in infants.

"Selective immunization of at-risk groups may reduce the incidence of hepatitis A infection, but only the inclusion of hepatitis A vaccine in a routine universal childhood immunization schedule would guarantee control of the infection. But the interference by maternally derived hepatitis A antibodies (anti-HAV) with the immunogenicity of inactivated hepatitis A vaccine is still important in the determination of the optimal age for hepatitis A vaccination," scientists in Turkey report.

"The hepatitis A vaccines have not been assessed widely in children under the age of 2 years and are not currently licensed for this age group in many countries. A prospective trial was performed to detect seroprevalence of maternal hepatitis A antibodies during the first 2 years of life among young infants born to hepatitis A antibody positive mothers in Turkey," said A. Derya and colleagues, Cukurova University.

"We measured at-birth anti-HAV in 147 infants born in our hospital and in their mothers and then from the offspring at months 3, 6, 9, 12, 15, 18, 21, and 24. The prevalence of seropositivity among the mothers at birth were found similarly high (93.9%) to the studies previously done among the adults in our area. The prevalence of anti-HAV among children aged 0, 9, 12, 15, 18, and 21 months were 93.9%, 62.6%, 36.1%, 13.6%, 6.1%, and 0.7%, respectively."

"Although a proportion of infants still had measurable antibodies at 9 and 12 month of age, two thirds of the infants over the age of 12 months were at high risk of acquiring hepatitis A infection, as living in an endemic region," researchers concluded.

Derya and colleagues published their study in American Journal of Tropical Medicine and Hygiene (Decline of maternal hepatitis A antibodies during the first 2 years of life in infants born in Turkey. Am J Trop Med Hyg, 2005;73(2):457-459).

For additional information, contact A. Derya, Cukurova University, Faculty Med, Dept. Pediatrics, Infectious Disease Unit, TR-01130 Adana, Turkey.

Keywords: Adana, Turkey, Child Immunization, Epidemiology, Hepatitis A Vaccine, Hepatitis A Virus, Hepatology, Immunology, Pediatrics, Obstetrics, Seroprevalence, Enteric Disease, Vaccination, Vaccine Research, Virology.

This article was prepared by Science Letter editors from staff and other reports. Copyright 2006, Science Letter via

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