RU2099086C1 - Method for prophylaxis of influenza in children by administering live influenza vaccine - Google Patents

Abstract

FIELD: medical virology; prophylaxis of epidemic influenza in 3- to 15- years-old children; pediatrics. SUBSTANCE: prophylaxis of influenza in children is achieved by intranasally administering to them live recombinant influenza vaccine prepared from cold-adapted attenuated strains of influenza viruses A and B, or from their recombinants prepared from cold-adapted attenuated strains. EFFECT: effective means for combatting influenza epidemics.

Description

 The invention relates to medical virology and can be used to prevent epidemic flu in children 3 to 15 years old. The most promising way to prevent viral infections, including the flu, is vaccination, which involves the use of live and inactivated vaccines.

 Inactivated whole-virion influenza vaccine causes adverse reactions in children 3 to 6 years old, especially from the blood. Split and subunit influenza inactivated vaccines do not meet the requirements of technological documentation for indicators of harmlessness and reactogenicity. The annual use of inactivated influenza vaccines for the same individuals results in a lack of protection.

 In Russia, a live influenza vaccine for adults has been developed and is being used in practice that is approved for use by adults over 15 years of age. This drug is not approved for use by children, as it can cause febrile reactions in them, i.e. flu disease.

 Therefore, there is a need to create a special version of the live influenza vaccine for children 3-15 years old, which would be harmless for children of preschool (3 6) and school (7 15) years of age. To do this, use more attenuated, extremely attenuated strains of the influenza virus. Such strains are obtained either by the method of successive passages of the virulent virus at a reduced temperature, while receiving the so-called cold-adapted (ha) variants, or by the method of genetic recombination, i.e. crossing a virulent virus with a cold-adapted variant. The resulting vaccine is administered intranasally to prevent influenza in children.

 Example 1

Virus A / Leningrad / 134/57 (Н2N2) was passaged 17 times at a temperature lowered to 25 ^o C. The resulting virus A / Leningrad / 134/17/57 (H2N2) has acquired signs of temperature sensitivity and cold adaptation. Intranasal immunization of children of 3–6 years old (1034 children) and 7–15 years old (6257 children) was organized with a vaccine from this strain. Reactogenicity, calculated by the number of temperature reactions (temperature more than 37.6 ^o C), did not exceed 1.0%, which corresponds to the requirements of FS 42-298 BC-89 for live influenza vaccine for children. Immunogenicity (i.e., the percentage of four or more multiple seroconversions, antibody growth in the blood) was more than 75%
Example 2

The virus B / Leningrad / 14/55 was passaged 17 times at a temperature of 25 ^o C. The resulting virus B / Leningrad / 14/17/55 acquired the sign of cold adaptation, by which it differed from the original virus B / Leningrad / 14/55. Organized intranasal immunization with a vaccine of strain B / Leningrad / 14/17/55 children 3 6 years old (4293 children) and 7 15 years (6736 children). Reactogenicity of the vaccine was 1.1%; immunogenicity 67.5%. Thus, according to these indicators, the vaccine meets the requirements of FS 42-298 BC-89.

 Example 3

 The immunization of 9054 children 3–6 years old with a divacina from strains A / Leningrad / 134/17/57 (Н2N2) and В / Leningrad / 14/17/55 was organized. Reactogenicity was 0% immunogenicity 66.6 66.3% respectively to strains A / Leningrad / 134/17/57 (H2N2) and B / Leningrad / 14/17/55.

 Example 4

A recombinant of the epidemic virulent virus A / Transcarpathia / 354/89 / BR and a cold-adapted strain A / Leningrad / 134/47/57 (H2N2) was prepared, which inherited from the virus A / Transcarpathia / 354/89 / BR surface hemagglutinin (GA) and neuraminidase (H), and the rest (internal genes) - from a cold-adapted strain, which determined its temperature sensitivity and cold-adaptation. A group of 101 children 3-14 years old was intranasally injected with the vaccine from the recombinant strain A / Transcarpathia / 354/89 / BR. Reactogenicity of the vaccine corresponded to 0% immunogenicity 70.3%
Example 5

Prepared recombinant B / 14/5/1 of the epidemic (virulent) virus B / Ann Arbor / 1/86 and a cold-adapted strain B / Leningrad / 14/17/55, which inherited hemagglutinin genes from the virus B / Ann / Arbor / 1/86 and neuraminidase, and the internal genes from the cold-adapted strain, which determined the temperature sensitivity and cold-adaptation of the recombinant B / 14/5/1. An intranasal immunization was carried out with a vaccine from strain B / 14/5/1 109 children 3-15 years old (34 children 3-6 years old, 75 children 7-15 years old). Reactogenicity of the vaccine was 1.3%; immunogenicity 70%
Example 6

 Intranasal vaccination of 108 children with a vaccine from two cold-adapted recombinants A / Taiwan / 1/86 (Н1N1) and В / 14/5/1 was carried out. Reactogenicity of divacin corresponded to 0% immunogenicity of 79.8% for component A (H1N1) and 50.0% for component B.

 Example 7

The reactogenic properties and antigenic activity of live influenza divactin A2 + B were studied in 511 children 3-12 years old. Reactogenicity of the vaccine was 0.3%; immunogenicity with respect to component A2 corresponded to 59.2% 75.0% to influenza B virus 42.3% 60.9%
Thus, the prophylaxis of influenza in children with a live influenza vaccine is achieved by using cold-adapted attenuated strains of the influenza A and B virus or recombinants derived from cold-adapted attenuated strains.

Claims (1)

A method for preventing influenza in children by intranasal administration of a live attenuated vaccine, characterized in that a cold-adapted vaccine based on attenuation donors A / Leningrad / 134/17/57 (H ₂ N ₂ ) and / or B / Leningrad / 14/17/55 is used obtained by the method of 17 consecutive passages in chicken embryos at 25 ^o C.