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SPECIFIC CHARACTERISTICS AND ANTIGENIC PROPERTIES OF THE
HEPATITIS VIRUS B
Tursunov Dilshodjon O'tkir o'g'li
Faculty of Medicine, International University of Asia, Uzbekistan.
https://doi.org/10.5281/zenodo.15185509
Abstract.
Hepatitis B remains a worldwide problem despite the availability of effective
vaccines. The hepatitis B virus surface antigen (HBsAg) induces a natural or postvaccine
humoral immune response directed primarily against the “a” determinant of HBsAg. This
determinant is part of the large hydrophilic region of HBsAg, located between the 124th and
147th amino acid residues (a. o.) forming 3 loops that are held together by disulfide bridges
formed by C124 and C137 a. o. and C139 and C147 a. o. [1]. This determinant has a highly
conformational nature and is universal, providing protection against all variants of hepatitis B
virus (HBV), so commercial hepatitis B vaccines include recombinant “a”-determinant HBsAg
as an immunogen [1].
Keywords:
Hepatitis B, HBsAg, monoclonal conjugates, recombinant, immunization.
СПЕЦИФИЧЕСКАЯ ХАРАКТЕРИСТИКА И АНТИГЕННЫЕ СВОЙСТВА ВИРУСА
ГЕПАТИТА В
Аннотация.
Гепатит В остается всемирной проблемой, несмотря на наличие
эффективных вакцин. Поверхностный антиген вируса гепатита В (HBsAg) вызывает
естественный или поствакцинальный гуморальный иммунный ответ, направленный в
первую очередь против детерминанты «a» HBsAg. Эта детерминанта является частью
большой гидрофильной области HBsAg, расположенной между 124-м и 147-м
аминокислотными остатками (а. о.), образующими 3 петли, которые удерживаются
вместе дисульфидными мостиками, образованными C124 и C137 а. и C139 и C147 а. [1].
Эта детерминанта имеет высококонформационную природу и является универсальной,
обеспечивая защиту от всех вариантов вируса гепатита В (HBV), поэтому коммерческие
вакцины против гепатита В включают в себя рекомбинантный «a»-детерминант HBsAg
в качестве иммуногена [1].
Ключевые
слова:
Гепатит
В,
HBsAg,
моноклональные
конъюгаты,
рекомбинантный, иммунизация.
Mass vaccination against hepatitis B promotes the selection and spread of mutant forms
of HBV that escape vaccine control (escape mutants). Amino acid substitutions within the “a”-
determinant lead to conformational changes and affect antigenicity and immunogenicity to
varying degrees. For example, the G145R substitution leads to such drastic changes that HBsAg-
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specific protective antibodies almost completely lose their ability to interact with the mutant
HBsAg variant [2-5]. However, such structural changes do not completely disrupt the
immunogenicity of HBsAg [6]. Infection of chimpanzees with a mutant virus isolate carrying the
G145R mutation results in the induction of an anti-HBs response [7]. The antigenic properties of
the native G145R mutant HBsAg, first detected in 1990, were analyzed [8]. [8], were analyzed
using 4 monoclonal antibodies binding to synthetic cyclic peptides consisting of 124-137 and
139-147 a. o. “a”-determinants.
A study of the interaction of anti-HBs from sera of over-vaccinated or vaccinated
individuals with the mutant G145R antigen showed that binding of anti-HBs to wild-type HBsAg
was completely inhibited by recombinant ay and ad. In contrast, no inhibition was observed with
mutant G145R HBsAg in the serum of vaccinated individuals, and minor inhibition was
observed in the serum of re-infected patients [5]. Other mutations in the 145th a. o. region did
not have such a pronounced effect. It has been shown that vaccination of humans with
preparations containing wild-type HBsAg induced antidiv formation to both wild-type HBsAg
and the S143L mutant with equal efficacy, but practically did not induce antidiv formation to
HBsAg carrying the G145R mutation [9, 10]. A study of the humoral response in BALB/c mice
after immunization with virus antigens belonging to the ay and ad subtypes of wild-type or
mutant G145R ay-type showed that HBsAg variants differ significantly in immunogenicity and
specificity of determinants [5]. In mice immunized with wild-type antigens, the anti-HBs
response was more than 100-fold higher than the immune response developed in the case of the
mutant antigen after the second immunization. When immunized with the ay subtype, anti-Au
antibodies were 4-fold higher than anti-G145R antibodies. In contrast, immunization with the
mutant antigen produced almost 5-fold more antibodies recognizing this mutant antigen than
antibodies recognizing wild-type. The results of the study of various recombinant and natural
variants of HBsAg by serological portrayal showed that recombinant wild-type ay and ad
antigens are recognized by the entire panel of conjugates This is consistent with the notion of the
universality of the “a”-determinant of HBsAg in wild-type HBV. Serologic portrayal of G145R
escapmutated antigens yielded heterogeneous results. Recombinant samples AHBV203 and
HBs-878 had no recognition defects by monoclonal conjugates, implying similarity in
conformation of these recombinant HBsAg wild-type HBsAg molecules. However, all
investigated recombinant antigens of the ESC series (HBsAg ayw2 subtype), also containing the
G145R mutation, had multiple deep “failures” in reactivity with most conjugates, and their
reactivity was almost identical to that of native HBsAg with the same mutation (ayw2 and adw3
subtypes) Nevertheless, the depth of recognition defects was not the same for different variants
of ESC antigens obtained under different experimental conditions.
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For example, the recognition impairments of the ESC-1 and ESC-2 antigens by the HB4
conjugate were almost 100-fold and by the X7 conjugate were 20-fold less than those of all three
natural isolates with the G145R mutation. In these antigens, the violations on conjugates 11F3
and 10D10 are also smaller than in the native mutant antigens and other recombinant variants
from the ESC series. This allows us to conclude that there is some disruption of the correct
folding of the ESC01 and ESC-02 antigens, which does not allow them to fully match the natural
conformation of the G145R mutant epitope. Therefore, these antigen variants cannot be used in
the development of specific vaccine components. In contrast, the serologic portrait of the ESC-
03 antigen is closest to the natural G145R HBsAg from sera 1537 and 2043, which have the
same subtype (ayw2), and this variant of specific antigen production seems to be preferred. The
results obtained indicate that the conditions of its expression and purification play no less
important role than nucleotide substitution in the targeting codon in obtaining recombinant
HBsAg with the G145R mutation, as the correct folding of the mutant antigen depends on them.
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