Abstract
One of the important reasons for spreading of hepatitis B virus (HBV) under conditions of vaccinepressure is emergence of escape mutations. Prevalent G145R mutation in S-gene leads to the most expressed changes of serological properties of HBV. Consequently, HBsAg is modifed so thoroughly that it cannot be recognized by the majority of anti-HBs. Mutant G145R also differs from a wild type HBsAg by its immunogenic properties. At present, the relevance of enhancement of hepatitis B vaccine in view of mutant virus variants has been recognized. a comparative study of antigenic and immunogenic properties of native and recombinant G145R mutants and an estimation of possibility for developing antigenic component of hepatitis B vaccine with G145R mutation in HBsAg. antigenic properties of recombinant HBsAg with G145R mutation were compared with each other and with native mutants by serological fngerprinting method. Then, BALB/c mice and sheep were immunized with selected recombinant antigen under different protocols. Titers of antibodies specifc to wild type or mutant G145R type of HBsAg in sera of immunized animals were measured. it was found that not all the recombinant HBsAg variants with G145R substitution have the same antigenic properties as native HBsAg with similar mutation. Recombinant HBsAg selected according to the principle of antigenic similarity possesses immunogenicity in mice and sheep causing the production of antibodies reacting with native wild and mutant type HBsAg. It was shown that mutant antigen is less immunogenic, requires larger doses and more time for the development of immune response; however, it is capable of causing an antibody level comparable with wild type antigen. preliminary selection of recombinant HBsAg containing G145R mutation with antigenic and immunogenic properties similar to the native analogue creates the basis for development of a specifc component of hepatitis B vaccine with escape mutation G145R in HBsAg.
Highlights
One of the important reasons for spreading of hepatitis B virus (HBV) under conditions of vaccine pressure is emergence of escape mutations
Mutant G145R differs from a wild type HBsAg by its immunogenic properties
Original research antigenic similarity possesses immunogenicity in mice and sheep causing the production of antibodies reacting with native wild and mutant type HBsAg
Summary
В результате HBsAg модифицируется столь значительно, что практически не распознается большинством анти-HBs. По иммуногенным свойствам мутант G145R также отличается от HBsAg дикого типа. Цель работы — сравнительное исследование антигенных и иммуногенных свойств природных и рекомбинантных мутантов G145R и оценка перспективы создания антигенного компонента вакцины против гепатита B с мутацией G145R в HBsAg. Методы. Отобранный по принципу антигенного сходства рекомбинантный HBsAg обладал иммуногенностью у мышей и овец, вызывая образование антител, реагирующих с нативным HBsAg дикого и мутантного типа. Предварительная селекция рекомбинантных HBsAg, содержащих мутацию G145R, по антигенным и иммуногенным свойствам близких нативному аналогу, дает основу для создания специфического компонента вакцины против гепатита В с эскейп-мутацией G145R в HBsAg. Ключевыеслова : мутация; S-ген; G145R; вирус гепатита В; рекомбинантный и нативный HBsAg; иммунизация. Сравнительная характеристика антигенных свойств рекомбинантных и нативных HBs-антигенов с мутацией G145R и оценка их иммуногенности. A COMPARATIVE CHARACTERISTIC OF ANTIGENIC PROPERTIES OF RECOMBINANT AND NATIVE HBs-ANTIGENS WITH G145R MUTATION AND EVALUATION OF THEIR IMMUNOGENICITY
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