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Far Eastern Journal of Infectious Pathology

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Chimeric virus-like particles that expose epitopes with HIV-1 broadly neutralizing antibodies

Abstract

All known approaches were tested in order to create a vaccine against HIV-1, however currently there is no effective vaccine against this pathogen. Relatively new and perspective approach involves rational design of immunizers aimed at focusing immune response against vulnerable virus regions. It is considered that highly conservative epitopes are located in protein-based regions and are essential for survival of the virus. Such epitopes can be regarded as ideal antigens for vaccine development. Core protein of Hepatitis B virus (HBcAg) that is regarded as a perspective platform for developing highly immunogenic vaccines was utilized as a carrier protein in current research. Because epitopes of a majority of broadly neutralizing antibodies are conformational current study utilized mediator-peptides that were obtained by means of phage display. Recombinant plasmids that contained epitopes and epitope imitators that are recognized by antibodies VRC34.01 and VRC01 respectively were derived on a basis of plasmid coding HBcAg. Electronic microscopy showed that chimeric variant НВсAg-c7cVRC01 forms particles of specific spherical shape. Immunological potency of obtained recombinant proteins was tested on rabbit model. It was revealed that animal serum that was immunized with chimeric variants of HBcAg had neutralizing activity against SF162.LS (subtype B) pseudovirus.

About the Authors

A. P. Rudometov
FBUN State research center of virology and biotechnology “Vector” of the Federal service for surveillance on consumers rights protection and human wellbeing
Russian Federation

Koltsovo



N. B. Rudometova
FBUN State research center of virology and biotechnology “Vector” of the Federal service for surveillance on consumers rights protection and human wellbeing
Russian Federation

Koltsovo



B. N. Zaitsev
FBUN State research center of virology and biotechnology “Vector” of the Federal service for surveillance on consumers rights protection and human wellbeing
Russian Federation

Koltsovo



A. A. Ilyichev
FBUN State research center of virology and biotechnology “Vector” of the Federal service for surveillance on consumers rights protection and human wellbeing
Russian Federation

Koltsovo



L. I. Karpenko
FBUN State research center of virology and biotechnology “Vector” of the Federal service for surveillance on consumers rights protection and human wellbeing
Russian Federation

Koltsovo



References

1. Рудометов А.П., Андреева Н.Б., Чикаев А.Н. и др. Антигенные свойства искусственного полиэпитопного ВИЧ-иммуногена // Сибирский научный медицинский журнал. – 2018. – Т. 38. – №. 4. – С. 37-43.

2. Рудометов А.П., Рудометова Н.Б., Зайцев Б.Н. и др. Получение химерных вариантов HBсAg, экспонирующих фрагменты MPER ВИЧ-1 // Сибирский научный медицинский журнал. – 2019. – Т. 39. – №. 4. – С. 55-61.

3. Рудометов А.П., Рудометова Н.Б., Щербаков Д.Н. и др. Исследование структурных и иммунологических свойств химерных белков, содержащих участки MPER ВИЧ-1 // Acta Naturae (русскоязычная версия). – 2019. – Т. 11. – №. 3 (42). – С. 56-65.

4. Щербаков Д.Н., Бакулина А.Ю., Карпенко Л.И., Ильичев А.А. Антитела, нейтрализующие широкий спектр изолятов ВИЧ-1, новая грань иммунной системы // Acta Naturae (русскоязычная версия). – 2015. – V. 7. – №. 4 (27).

5. Arora U., Tyagi P., Swaminathan S., Khannaet N. Chimeric Hepatitis B core antigen virus-like particles displaying the envelope domain III of dengue virus type 2 // Journal of Nanobiotechnology. – 2012. – V. 10. – №. 30. – P. 1–6.

6. Bachmann M.F., Jennings G.T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns // Nature Reviews Immunology. – 2010. – V. 10. – №. 11. – P. 787-796.

7. Chikaev A.N., Bakulina A.Y., Burdick R.C. et al. Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01 // PloS one. – 2015. – V. 10. – №. 3.

8. Eisinger R.W., Fauci A.S. Ending the HIV/AIDS pandemic // Emerging infectious diseases. – 2018. – V. 24. – №. 3. – P. 413.

9. Hessell A.J., Jaworski J.P., Epson E. et al. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques // Nature medicine. – 2016. – V. 22. – №. 4. – P. 362-368.

10. Kanekiyo M., Bu W., Joyce M.G. et al. Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site // Cell. – 2015. – V. 162. – №. 5. – P. 1090-1100.

11. Kong R., Xu K., Zhou T. et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody // Science. – 2016. – V. 352. – №. 6287. – P. 828-833.

12. Lorenzo-Redondo R., Fryer H.R., Bedford T. et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy // Nature. – 2016. – V. 530. – №. 7588. – P. 51-56.

13. Pumpens P., Grens E. The true story and advantages of the famous Hepatitis B virus core particles: Outlook 2016 //Molecular Biology. – 2016. – Т. 50. – №. 4. – С. 489-509.

14. Rudometov A.P., Chikaev A.N., Rudometova N.B. et al. Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope // Vaccines. – 2019. – V.7.– №. 3. – P.1-18.


Review

For citations:


Rudometov A.P., Rudometova N.B., Zaitsev B.N., Ilyichev A.A., Karpenko L.I. Chimeric virus-like particles that expose epitopes with HIV-1 broadly neutralizing antibodies. Far Eastern Journal of Infectious Pathology. 2020;(39):40-45. (In Russ.)

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ISSN 2073-2899 (Print)