Uz rekombinanto Semliki meža vīrusu balstīta pieeja uzlabotas vakcīnas pret B hepatīta vīrusu meklējumos: neitralizējošu antivielu ierosināšana
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Latvijas Universitāte
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Abstract
Ar Semliki meža vīrusa vektoriem ierosināta neitralizējošu antivielu
veidošanās pret B hepatīta vīrusa (HBV) virsmas proteīniem, lai pētītu iespējamos
risinājumus patlaban izmantotās HBV vakcīnas nepilnībām - tā sastāv no viena HBV
S virsmas proteīna subtipa, kas ekspresēts raugā, un atbilst vienam vīrusa genotipam.
Ierosinātas neitralizējošas antivielas pret S proteīna diviem subtipiem, kas atbilst
diviem vīrusa genotipiem, kā arī, lai paplašinātu imūno atbildi, pret saīsinātu L
proteīnu, kas ietver divus par HBV saistīšanos pie hepatocītiem atbildīgos rajonus.
Antivielu saistīšanās pie rekombinantā raugā ekspresētā HBsAg bija atkarīga no tā
apakštipa, kamēr saistīšanās pie HBsAg, kas iegūts no HBV pacientiem, nebija
atkarīga no apakštipa. Izmantojot HBV infekcijas in vitro modeli, parādīts, ka ar rSFV
ierosināto antivielu neitralizējošais potenciāls nebija atkarīgs no S apakštipa.
Atslēgas vārdi: B hepatīta vīrusa virsmas proteīni; apakštips; Semliki meža vīrusa
vektors; neitralizējošas antivielas
Semliki Forest virus vector (rSFV) approach was exploited for generation of neutralizing antibodies to surface proteins of hepatitis B virus (HBV) to address potential problems associated with current HBV vaccine, which consists of yeastexpressed small (S) protein, subtype ayw2, virus genotype A. After rSFV mediated delivery neutralizing antibodies were induced in mice to two S subtypes, representing different virus genotypes, and to shortened large proteins comprised of both HBV attachment determinants. Antibodies demonstrated preference to homologous subtype determinant of yeast-derived recombinant HBsAg, while binding to patient-derived HBsAg was not subtype dependent. In vitro HBV infection model showed that neutralizing antibodies were S subtype independent. The findings show that subtype dependency may not be as pronounced with vector-type vaccines. Keywords: Hepatitis B virus surface proteins; subtype; recombinant Semliki Forest virus vector, neutralizing antibodies.
Semliki Forest virus vector (rSFV) approach was exploited for generation of neutralizing antibodies to surface proteins of hepatitis B virus (HBV) to address potential problems associated with current HBV vaccine, which consists of yeastexpressed small (S) protein, subtype ayw2, virus genotype A. After rSFV mediated delivery neutralizing antibodies were induced in mice to two S subtypes, representing different virus genotypes, and to shortened large proteins comprised of both HBV attachment determinants. Antibodies demonstrated preference to homologous subtype determinant of yeast-derived recombinant HBsAg, while binding to patient-derived HBsAg was not subtype dependent. In vitro HBV infection model showed that neutralizing antibodies were S subtype independent. The findings show that subtype dependency may not be as pronounced with vector-type vaccines. Keywords: Hepatitis B virus surface proteins; subtype; recombinant Semliki Forest virus vector, neutralizing antibodies.