ПОСТВАКЦИНАЛЬНЫЙ ИММУННЫЙ ОТВЕТ У СЕРОНЕГАТИВНЫХ К ВИРУСУ ГРИППА БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ

The purpose of the study. To evaluate immunogenicity of influenza vaccination in HIV-infected adults initially seronegative to influenza virus.Materials and methods. There were 175 HIV-infected persons and 50 healthy volunteers vaccinated against influenza in Republican center of AIDS (Ufa) in 2016-November. Titers of antibodies to influenza virus (A [H1N1], A [H3N2] and B) were detected in standard hemagglutination-inhibition reaction: before (day 0) and after (on 21th and 150th days) vaccination. Post-vaccination trends of antibodies to influenza virus were analyzed in 12 HIV-infected patients (7%) and 13 subjects from control group (26%) with the titer of antibodies lower than protective level (1/40) according to the criteria of immunogenicity for influenza vaccines for all subtypes of its antigens.Results. The shares of initially seronegative were 2–7% for HIV-infected and 12–24% Saint-Petersburg for healthy persons. Seroconversion coefficient varied from 1,6 to 2,3; seroconversion rate varied from 0 to 25%; seroprotection rate – from 67% for А (H1N1) to 100% for А (H3N2) and В. The titer of antibodies detected on day 21 didn’t decrease up to day 150 in all vaccinated persons.The analysis of the titer in HIV-infected adults with the different levels of CD4-cells demonstrated achievement of minimal protective level (1/40) in the majority of cases, and at least fourfold increase of the titer was determined when CD4-cells level was 350 cells/μl.Conclusion. Single immunization of HIV-infected adults with standard vaccine for seasonal prevention of influenza is insufficient for creation of adequate immune response. A small sample of the study does not allow extrapolating the results of studies to large cohorts of patients with HIV infection. Further research is required to develop recommendations for vaccine prevention of influenza in patients with HIV infection.Цель: оценка иммуногенности вакцинации от гриппа ВИЧ-инфицированных взрослых, исходно серонегативных к вирусу гриппа.Материалы и методы: вакцинировали от гриппа 175 ВИЧ-инфицированных и 50 здоровых добровольцев на базе Республиканского центра по профилактике и борьбе со СПИД г. Уфы в ноябре 2016 г. Определяли титр гемагглютинирующих антител к антигенам вируса гриппа А (H1N1), А (H3N2) и В в стандартной реакции торможения гемагглютинации до вакцинации (0 день), на 21-й и 150-й дни после вакцинации. Анализ поствакцинальной динамики антител к вирусу гриппа провели у 12 больных ВИЧ- инфекцией (7%) и 13 человек из контрольной группы (26%) с титром антител ниже протективного значения (1/40) согласно критериям иммуногенности противогриппозных вакцин для всех субтипов антигенов вакцины.Результаты: от 2 до 7% ВИЧ-инфицированных и от 12 до 24% здоровых лиц были исходно серонегативны к антигенам трех вирусов гриппа. Коэффициент сероконверсии варьировал от 1,6 до 2,3; показатель сероконверсии составил от 0 до 25%; показатель серопротекции от 67% к антигену А (H1N1) до 100% к антигенам А (H3N2) и В. Титр антител, выработанный к 21-му дню, у всех привитых не снижался до 150-го дня после вакцинации.Анализ у ВИЧ-инфицированных с разным количеством CD4-лимфоцитов показал, что большинство привитых вырабатывают минимальное протективное количество антител (1/40); при уровне CD4-лимфоцитов более 350 кл/мкл наблюдали четырехкратный и более рост титра в динамике.Заключение: однократная иммунизация ВИЧ- инфицированных стандартной вакциной для сезонной профилактики гриппа недостаточна для формирования полноценного иммунного ответа. Малая выборка исследования не позволяет экстраполировать результаты исследования на большие когорты больных ВИЧ- инфекцией. Для разработки рекомендаций по вакцинопрофилактике гриппа у больных ВИЧ-инфекцией требуются дальнейшие исследования.

POST-VACCINATION IMMUNE RESPONCE IN SERONEGATIVE TO INFLUENZA VIRUS HIV-INFECTED PATIENTS

The purpose of the study. To evaluate immunogenicity of influenza vaccination in HIV-infected adults initially seronegative to influenza virus.Materials and methods. There were 175 HIV-infected persons and 50 healthy volunteers vaccinated against influenza in Republican center of AIDS (Ufa) in 2016-November. Titers of antibodies to influenza virus (A [H1N1], A [H3N2] and B) were detected in standard hemagglutination-inhibition reaction: before (day 0) and after (on 21th and 150th days) vaccination. Post-vaccination trends of antibodies to influenza virus were analyzed in 12 HIV-infected patients (7%) and 13 subjects from control group (26%) with the titer of antibodies lower than protective level (1/40) according to the criteria of immunogenicity for influenza vaccines for all subtypes of its antigens.Results. The shares of initially seronegative were 2–7% for HIV-infected and 12–24% Saint-Petersburg for healthy persons. Seroconversion coefficient varied from 1,6 to 2,3; seroconversion rate varied from 0 to 25%; seroprotection rate – from 67% for А (H1N1) to 100% for А (H3N2) and В. The titer of antibodies detected on day 21 didn’t decrease up to day 150 in all vaccinated persons.The analysis of the titer in HIV-infected adults with the different levels of CD4-cells demonstrated achievement of minimal protective level (1/40) in the majority of cases, and at least fourfold increase of the titer was determined when CD4-cells level was 350 cells/μl.Conclusion. Single immunization of HIV-infected adults with standard vaccine for seasonal prevention of influenza is insufficient for creation of adequate immune response. A small sample of the study does not allow extrapolating the results of studies to large cohorts of patients with HIV infection. Further research is required to develop recommendations for vaccine prevention of influenza in patients with HIV infection

Numerical Matrices Method for Nonlinear System Identification and Description of Dynamics of Biochemical Reaction Networks

A flexible Numerical Matrices Method (NMM) for nonlinear system identification has been developed based on a description of the dynamics of the system in terms of kinetic complexes. A set of related methods are presented that include increasing amounts of prior information about the reaction network structure, resulting in increased accuracy of the reconstructed rate constants. The NMM is based on an analytical least squares solution for a set of linear equations to determine the rate parameters. In the absence of prior information, all possible unimolecular and bimolecular reactions among the species in the system are considered, and the elements of a general kinetic matrix are determined. Inclusion of prior information is facilitated by formulation of the kinetic matrix in terms of a stoichiometry matrix or a more general set of representation matrices. A method for determination of the stoichiometry matrix beginning only with time-dependent concentration data is presented. In addition, we demonstrate that singularities that arise from linear dependencies among the species can be avoided by inclusion of data collected from a number of different initial states. The NMM provides a flexible set of tools for analysis of complex kinetic data, in particular for analysis of chemical and biochemical reaction networks