title: Development of a hybrid vaccine prototype against both lineages of Influenza B virus
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Ð Ð°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ° Ð¿ÑÐ¾ÑÐ¾ÑÐ¸Ð¿Ð° Ð³Ð¸Ð±ÑÐ¸Ð´Ð½Ð¾Ð¹ Ð²Ð°ÐºÑÐ¸Ð½Ñ Ð¿ÑÐ¾ÑÐ¸Ð² Ð¾Ð±ÐµÐ¸Ñ Ð»Ð¸Ð½Ð¸Ð¹ Ð²Ð¸ÑÑÑÐ° Ð³ÑÐ¸Ð¿Ð¿Ð° Ð
Creators: name: ÐÐ¾Ð½ ÐÑÐ¹ Ð¤Ð¾Ð½
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2023
Subjects: ÐÐ¸ÑÑÑÐ¾Ð»Ð¾Ð³Ð¸Ñ
ÐÐ¸Ð¾ÑÐµÑ Ð½Ð¾Ð»Ð¾Ð³Ð¸Ñ
Ð²Ð¸ÑÑÑ Ð³ÑÐ¸Ð¿Ð¿Ð° Ð
Ð¶Ð¸Ð²Ð°Ñ Ð°ÑÑÐµÐ½ÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½Ð°Ñ Ð³ÑÐ¸Ð¿Ð¿Ð¾Ð·Ð½Ð°Ñ Ð²Ð°ÐºÑÐ¸Ð½Ð°
Ð¾Ð±ÑÐ°ÑÐ½Ð°Ñ Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ°
ÑÐµÐºÐ¾Ð¼Ð±Ð¸Ð½Ð°Ð½ÑÐ½ÑÐ¹ Ð²Ð¸ÑÑÑ Ð³ÑÐ¸Ð¿Ð¿Ð°
Ð¿ÐµÑÐµÐºÑÐµÑÑÐ½Ð°Ñ Ð·Ð°ÑÐ¸ÑÐ°
Ð¿Ð¾ÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð°Ñ Ð²Ð°ÐºÑÐ¸Ð½Ð°ÑÐ¸Ñ
Ð²Ð¸ÑÑÑÐ½ÑÐ¹ Ð¸Ð¼Ð¼ÑÐ½Ð¸ÑÐµÑ
influenza B virus
live attenuated influenza vaccine
reverse genetics
recombinant influenza virus
cross-protection
sequential vaccination
viral immunity

description: Ð¢ÐµÐ¼Ð° Ð²ÑÐ¿ÑÑÐºÐ½Ð¾Ð¹ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÑ: Â«Ð Ð°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ° Ð¿ÑÐ¾ÑÐ¾ÑÐ¸Ð¿Ð° Ð³Ð¸Ð±ÑÐ¸Ð´Ð½Ð¾Ð¹ Ð²Ð°ÐºÑÐ¸Ð½Ñ Ð¿ÑÐ¾ÑÐ¸Ð² Ð¾Ð±ÐµÐ¸Ñ Ð»Ð¸Ð½Ð¸Ð¹ Ð²Ð¸ÑÑÑÐ° Ð³ÑÐ¸Ð¿Ð¿Ð° ÐÂ». ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐºÐµ Ð¿ÑÐ¾ÑÐ¾ÑÐ¸Ð¿Ð° Ð¶Ð¸Ð²Ð¾Ð¹ Ð³ÑÐ¸Ð¿Ð¿Ð¾Ð·Ð½Ð¾Ð¹ Ð²Ð°ÐºÑÐ¸Ð½Ñ (ÐÐÐ), ÑÐ¿Ð¾ÑÐ¾Ð±Ð½Ð¾Ð¹ Ð¾Ð±ÐµÑÐ¿ÐµÑÐ¸ÑÑ Ð·Ð°ÑÐ¸ÑÑ Ð¾Ñ Ð´Ð²ÑÑ Ð³ÐµÐ½ÐµÑÐ¸ÑÐµÑÐºÐ¸Ñ Ð»Ð¸Ð½Ð¸Ð¹ Ð²Ð¸ÑÑÑÐ° Ð³ÑÐ¸Ð¿Ð¿Ð° ÑÐ¸Ð¿Ð° Ð. ÐÐ»Ñ Ð¿Ð¾Ð»ÑÑÐµÐ½Ð¸Ñ Ð²Ð°ÐºÑÐ¸Ð½Ð½ÑÑ ÑÑÐ°Ð¼Ð¼Ð¾Ð² LAIV Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ Ð¾Ð±ÑÐ°ÑÐ½Ð¾Ð¹ Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ¸ Ð²ÑÐµ Ð³ÐµÐ½Ñ Ð°ÑÑÐµÐ½ÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð³Ð¾ Ð´Ð¾Ð½Ð¾ÑÐ°, ÑÑÐ°Ð¼Ð¼Ð° B/USSR/60/69 (B60), ÐºÐ»Ð¾Ð½Ð¸ÑÐ¾Ð²Ð°Ð»Ð¸ Ð² Ð´Ð²ÑÐ½Ð°Ð¿ÑÐ°Ð²Ð»ÐµÐ½Ð½ÑÐµ Ð²ÐµÐºÑÐ¾ÑÑ. ÐÐµÐ½Ð½Ð¾-Ð¸Ð½Ð¶ÐµÐ½ÐµÑÐ½ÑÐ¹ ÑÑÐ°Ð¼Ð¼ Ð60-Ð Ð (ÐÐ±ÑÐ°ÑÐ½Ð°Ñ Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ°) Ð¿Ð¾ ÑÐ²Ð¾Ð¸Ð¼ ÑÐµÐ½Ð¾ÑÐ¸Ð¿Ð¸ÑÐµÑÐºÐ¸Ð¼ ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸ÑÑÐ¸ÐºÐ°Ð¼ Ð½Ðµ Ð¾ÑÐ»Ð¸ÑÐ°Ð»ÑÑ Ð¾Ñ Ð¸ÑÑÐ¾Ð´Ð½Ð¾Ð³Ð¾ ÑÑÐ°Ð¼Ð¼Ð° Ð60, ÑÑÐ¾ Ð¿ÑÐµÐ´ÑÑÐ°Ð²Ð»ÑÐµÑ Ð±Ð¾Ð»ÑÑÑÑ Ð¿ÐµÑÑÐ¿ÐµÐºÑÐ¸Ð²Ñ Ð´Ð»Ñ ÑÐ¾Ð·Ð´Ð°Ð½Ð¸Ñ Ð³ÐµÐ½Ð½Ð¾-Ð¸Ð½Ð¶ÐµÐ½ÐµÑÐ½ÑÑ Ð²Ð°ÐºÑÐ¸Ð½Ð½ÑÑ ÑÑÐ°Ð¼Ð¼Ð¾Ð². Ð ÑÐ°Ð±Ð¾ÑÐµ Ð¿Ð¾Ð»ÑÑÐµÐ½Ñ Ð´Ð²Ð° Ð¿ÑÐ¾ÑÐ¾ÑÐ¸Ð¿Ð° Ð³Ð¸Ð±ÑÐ¸Ð´Ð½ÑÑ Ð²Ð°ÐºÑÐ¸Ð½Ð½ÑÑ ÑÑÐ°Ð¼Ð¼Ð¾Ð², Ð¾Ð´Ð¸Ð½ Ð¸Ð· ÐºÐ¾ÑÐ¾ÑÑÑ ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÐµÑ Ð¼Ð¾Ð»ÐµÐºÑÐ»Ñ Ð³ÐµÐ¼Ð°Ð³Ð³Ð»ÑÑÐ¸Ð½Ð¸Ð½Ð° (ÐÐ) Ð¸Ð· Ð²Ð¸ÑÑÑÐ° Ð»Ð¸Ð½Ð¸Ð¸ Victoria Ð¸ Ð½ÐµÐ¹ÑÐ°Ð¼Ð¸Ð½Ð¸Ð´Ð°Ð·Ñ (NA) Ð¸Ð· ÑÑÐ°Ð¼Ð¼Ð° Ð»Ð¸Ð½Ð¸Ð¸ Yamagata (HBNP), Ð° Ð²ÑÐ¾ÑÐ¾Ð¹ ÑÐºÑÐ¿ÑÐµÑÑÐ¸ÑÑÐµÑ HA Ð¸Ð· Ð»Ð¸Ð½Ð¸Ð¸ Yamagata. Ð²Ð¸ÑÑÑ Ð¸ NA Ð¸Ð· Ð»Ð¸Ð½Ð¸Ð¸ Victoria (HPNB). Ð¡ÐºÐ¾Ð½ÑÑÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐµ Ð²Ð¸ÑÑÑÑ Ð¾Ð±Ð»Ð°Ð´Ð°Ð»Ð¸ Ð±Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¼Ð¸ ÑÐ²Ð¾Ð¹ÑÑÐ²Ð°Ð¼Ð¸, ÑÐ°ÑÐ°ÐºÑÐµÑÐ½ÑÐ¼Ð¸ Ð´Ð»Ñ ÐºÐ»Ð°ÑÑÐ¸ÑÐµÑÐºÐ¸Ñ ÑÑÐ°Ð¼Ð¼Ð¾Ð² ÐÐÐ ÑÐ¸Ð¿Ð° Ð. ÐÐ¼Ð¼ÑÐ½Ð¸Ð·Ð°ÑÐ¸Ñ Ð¼ÑÑÐµÐ¹ Ð¿ÑÐ¾ÑÐ¾ÑÐ¸Ð¿Ð°Ð¼Ð¸ Ð²Ð°ÐºÑÐ¸Ð½ Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ð»Ð° Ðº Ð¾Ð±ÑÐ°Ð·Ð¾Ð²Ð°Ð½Ð¸Ñ Ð²ÑÑÐ¾ÐºÐ¸Ñ ÑÑÐ¾Ð²Ð½ÐµÐ¹ Ð°Ð½ÑÐ¸Ð³ÐµÐ¼Ð°Ð³Ð³Ð»ÑÑÐ¸Ð½Ð¸Ð½Ð¾Ð²ÑÑ Ð°Ð½ÑÐ¸ÑÐµÐ» (ÐÑ) Ðº Ð²Ð¸ÑÑÑÐ°Ð¼, ÑÐ¾Ð´ÐµÑÐ¶Ð°ÑÐ¸Ð¼ Ð³Ð¾Ð¼Ð¾Ð»Ð¾Ð³Ð¸ÑÐ½ÑÐ¹ Ð°Ð½ÑÐ¸Ð³ÐµÐ½ ÐÐ. ÐÐ½Ð°Ð»Ð¸Ð· Ð¸Ð¼Ð¼ÑÐ½Ð½Ð¾Ð³Ð¾ Ð¾ÑÐ²ÐµÑÐ° Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ ÐÐ¤Ð Ð½Ð° ÑÐµÐ»ÑÐ½ÑÐµ Ð²Ð¸ÑÑÑÐ½ÑÐµ Ð°Ð½ÑÐ¸Ð³ÐµÐ½Ñ Ð²ÑÑÐ²Ð¸Ð» Ð²ÑÑÐ¾ÐºÐ¸Ð¹ ÑÑÐ¾Ð²ÐµÐ½Ñ Ð¿ÐµÑÐµÐºÑÐµÑÑÐ½Ð¾Ð¹ ÑÐµÐ°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ ÑÑÐ²Ð¾ÑÐ¾ÑÐ¾ÑÐ½ÑÑ Ð°Ð½ÑÐ¸ÑÐµÐ» IgG, ÑÐ¾Ð³Ð´Ð° ÐºÐ°Ðº ÑÐ¾ÑÐµÑÐ°Ð½Ð¸Ðµ Ð¿Ð¾Ð²ÐµÑÑÐ½Ð¾ÑÑÐ½ÑÑ Ð°Ð½ÑÐ¸Ð³ÐµÐ½Ð¾Ð² Ð² ÑÐ¾ÑÑÐ°Ð²Ðµ Ð³Ð¸Ð±ÑÐ¸Ð´Ð½ÑÑ Ð²Ð°ÐºÑÐ¸Ð½Ð½ÑÑ ÑÑÐ°Ð¼Ð¼Ð¾Ð² HBNP Ð¸ HPNB Ð¿Ð¾Ð²ÑÑÐ°Ð»Ð¾ ÑÑÐ¾Ð²ÐµÐ½Ñ Ð°Ð½ÑÐ¸ÑÐµÐ» Ðº Ð²Ð¸ÑÑÑÑ Ð¾Ñ Ñ ÐºÐ¾ÑÐ¾ÑÑÑ Ð³ÐµÐ½ NA Ð±ÑÐ» ÑÐ½Ð°ÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½ Ð¿Ð¾ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ñ Ñ ÐºÐ»Ð°ÑÑÐ¸ÑÐµÑÐºÐ¸Ð¼Ð¸ ÑÑÐ°Ð¼Ð¼Ð°Ð¼Ð¸ LAIV Ð»Ð¸Ð½Ð¸Ð¸ Victoria Ð¸ Ð»Ð¸Ð½Ð¸Ð¸ Yamagata ÑÐ¾Ð¾ÑÐ²ÐµÑÑÑÐ²ÐµÐ½Ð½Ð¾. ÐÑÐµÐ´ÑÑÐ°Ð²Ð»ÐµÐ½Ð½Ð°Ñ ÑÑÑÐ°ÑÐµÐ³Ð¸Ñ Ð¼Ð¾Ð¶ÐµÑ Ð±ÑÑÑ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð° ÐºÐ°Ðº Ð¾ÑÐ½Ð¾Ð²Ð° Ð´Ð»Ñ ÑÐ¾Ð·Ð´Ð°Ð½Ð¸Ñ Ð²Ð°ÐºÑÐ¸Ð½Ñ ÑÐ¸ÑÐ¾ÐºÐ¾Ð³Ð¾ ÑÐ¿ÐµÐºÑÑÐ° Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ Ð¿ÑÐ¾ÑÐ¸Ð² Ð°Ð½ÑÐ¸Ð³ÐµÐ½Ð½Ð¾ ÑÐ´Ð°Ð»ÐµÐ½Ð½ÑÑ Ð²Ð°ÑÐ¸Ð°Ð½ÑÐ¾Ð² Ð²Ð¸ÑÑÑÐ° Ð³ÑÐ¸Ð¿Ð¿Ð° Ð.
description: The subject of the graduate qualification work is âDevelopment of a hybrid vaccine prototype against both lineages of Influenza B virusâ. This work is devoted to the development of a prototype live influenza vaccine (LAIV) capable of providing protection against two genetic lines of type B influenza virus. To obtain LAIV vaccine strains by reverse genetics, all genes of the attenuated donor, strain B/USSR/60/69 (B60), were cloned into bidirectional vectors. The genetically engineered B60-RG (Reverse genetics) strain did not differ in its phenotypic characteristics from the original B60 strain, which presents a better prospect for the construction of genetically engineered vaccine strains. Two prototypes of hybrid vaccine strains were obtained in the work, one of which expresses the hemagglutinin (HA) molecule from the Victoria lineage virus and neuraminidase (NA) from the Yamagata lineage strain (HBNP), and the second expresses HA from the Yamagata lineage virus and NA from the Victoria lineage (HPNB). The engineered viruses possessed the biological properties characteristic of classical strains of type B LAIV. Immunization of mice with vaccine prototypes resulted in the formation of high levels of anti-hemagglutinin antibodies (Abs) to viruses containing the homologous HA antigen. Analysis of the immune response by ELISA to whole viral antigens revealed a high level of cross-reactivity of serum IgG Abs, while the combination of surface antigens in the composition of the hybrid vaccine strains HBNP and HPNB increased the levels of Abs to the virus from which the NA gene was inherited, relative to the classical LAIV strains of the Victoria lineage and the Yamagata lineage, respectively. The presented strategy can be used as a basis for creating a broad-spectrum vaccine against antigenically deleted variants of the influenza B virus.