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0007-4888/18/16460743--©-2018--Springer-Science+Business-Media,-LLC
Bulletin of Experimental Biology and Medicine, Vol. 164, No. 6, April, 2018
VIROLOGY
Modeling of 3D Structure of Chimeric Constructs Based
on Hemagglutinin of Infuenza Virus and Immunogenic
Epitopes of Streptococcus Agalactiae
E. A. Fedorova
1
, T. A. Smolonogina
1
, I. N. Isakova-Sivak
1
, D. A. Koren’kov
1
,
T. S. Kotomina
1
, G. F. Leont’eva
2
, A. N. Suvorov
2
, and L. G. Rudenko
1
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 12, pp. 712-717, December, 2017
Original article submitted June 28, 2017
A project of an experimental recombinant vector vaccine for prevention of diseases caused by
pathogenic streptococci based on ScaAB lipoprotein of Streptococcus agalactiae and a cold-
adapted strain of live infuenza vaccine as a vector was developed. The sequence of ScaAB
lipoprotein was analyzed and fragments forming immunodominant epitopes were determined.
Chimeric molecules of infuenza virus hemagglutinin H7 carrying insertions of bacterial
origin were constructed. Based on the results of simulation, the most promising variants
were selected; they represented fragments of lipoprotein ScaAB lacking N-terminal domain
bound to hemagglutinin via a fexible linker. These insertions should minimally modulate the
properties of the infuenza strain, while retaining potential immunogenicity to a wide group
of pathogenic streptococci.
Key Words: vector vaccine; infuenza viruses; group B Streptococci
1
A. A. Smorodintsev Department of Virology,
2
Department of Mo-
lecular Microbiology, Institute of Experimental Medicine, St. Peters-
burg, Russia. Address for correspondence: fedorova.iem@gmail.
com. E. A. Fedorova
Group B streptococci (Streptococcus agalactiae) the
most common bacterial pathogens that causes a variety
of severe diseases of newborns, pregnant women, and
elderly people. The most dangerous manifestations
of infection are sepsis and meningitis of newborns,
as well as septicemia that develops in frail elderly
patients. The development of antibiotic resistance in
Streptococcus strains raises a question of effective
prevention of the infection. The development of vac-
cines against streptococcal infection requires special
techniques: traditional approaches cannot be used
due to unsatisfactory safety or immunogenicity of the
preparations [6].
An alternative approach is the use of vector vac-
cine. Competent design of the vaccine allows achiev-
ing complex stimulation of the immune response
while maintaining safety. Cold-adapted infuenza vi-
rus, live attenuated infuenza vaccine (LAIV) strain,
can be used as the vector system. The safety of the
vaccine is confrmed by long experience of long-term
use of the drug in humans, as well as the presence of
many attenuating mutations in genes of the vaccine
strain [11,12]. The possibility of genetic manipula-
tions with this cold-adapted strain is provided by
the previously developed reverse genetic system [7].
Alien genetic information can be inserted in various
genetic segments of the infuenza A virus. Infuenza
A viruses with recombinant genes of hemaggluti-
nin, neuraminidase, and nonstructural protein were
constructed [3,4]. Viruses with recombinant hemag-
glutinin stimulate humoral immunity to the inserted
DOI 10.1007/s10517-018-4071-4