New Approaches to the Development of Immunogen for HIV Vaccine

 
PIIS0032874X0002319-9-1
DOI10.31857/S0032874X0002319-9
Publication type Article
Status Published
Authors
Affiliation:
Ivanovsky Institute of Virology, Gamaleya Federal Research Center of Epidemiology and Microbiology
Faculty of Biology, Lomonosov Moscow State University
Address: Russian Federation, Moscow
Journal namePriroda
EditionIssue №11
Pages3-11
Abstract

The most effective anti-HIV antibodies capable of blocking extracellular and intracellular HIV are antibodies against conserved epitopes on the Env-trimer obtained from HIV-infected individuals. A multi-step strategy for the design of new immunogens based on Envtrimers has been developed. A strategy developed on the basis of the data obtained during the study of HIV escape from the immune response mechanisms was used for the modification. Modification of the cytoplasmic domain, made it possible to obtain stabilized open-form trimers. Another modification of the trans-membrane domain (TMS) in combination with the short cytoplasmic tail enhanced the incorporation of Env-trimers.

into viruslike particles (VLP). Stepbystep modification VLPbased immunogens are capable of inducing protective

high avidity and broadly neutralizing antibodies and have great potential for the development of HIV vaccines.

KeywordsHIV, broadly neutralizing antibodies, protective non-neutralizing antibodies, Env-trimers, immunogen design
Received06.12.2018
Publication date11.12.2018
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1. Parsons M.S., Lloyd S.B., Lee W.S. et al. Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection. Sci. Transl. Med. 2017; 9(402): eaaf1483. Doi:10.1126/scitranslmed.aaf1483.

2. Hessell A.J., Poignard P., Hunter M. et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat. Med. 2009; 15(8): 951–954. Doi:10.1038/nm.1974.

3. Robinson H.L. Non-neutralizing antibodies in prevention of HIV infection. Expert. Opin. Biol. Ther. 2013; 13(2):197–207. Doi:10.1517 / 14712598.2012.743527.

4. Vzorov A.N., Uryvaev L.V. Requirements for the Induction of Broadly Neutralizing Antibodies against HIV-1 by Vaccination. Mol. Biol. 2017; 51(6): 819–829. Doi:10.1134/S0026893317060176.

5. Manrique A., Adams E., Barouch D.H. et al. The immune space: a concept and template for rationalizing vaccine development. AIDS Res. Hum. Retroviruses. 2014; 30(11):1017–1022. Doi:10.1089/AID.2014.0040.

6. Havenar-Daughton C., Carnathan D.G., Torrents de la Pena A. et al. Direct probing of germinal center responses reveals immunological features and bottlenecks for neutralizing antibody responses to HIV Env trimer. Cell Rep. 2016; 17(9):2195–2209. Doi:10.1016/j.celrep.2016.10.085.

7. Haynes B.F., Kelsoe G., Harrison S.C., Kepler T.B. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat. Biotechnol. 2012; 30: 423–433. Doi:10.1038 / nbt.2197.

8. Cheeseman H.M., Olejniczak N.J., Rogers P.M. et al. Broadly neutralizing antibodies display potential for prevention of HIV-1 infection of mucosal tissue superior to that of nonneutralizing antibodies. J. Virol. 2017, 91(1): e01762-16. Doi:10.1128 / JVI.01762-16.

9. Mabuka J., Nduati R., Odem-Davis K. et al. HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads. PLoS Pathog. 2012; 8(6): e1002739. Doi:10.1371/journal.ppat.1002739.

10. Alexander M.R., Sanders R.W., Moore J.P., Klasse P.J. Short communication: virion aggregation by neutralizing and nonneutralizing antibodies to the HIV-1 envelope glycoprotein. AIDS Res. Hum. Retroviruses. 2015; 31(11): 1160–1165. Doi:10.1089/aid.2015.0050.

11. Kwong P.D. What are the most powerful immunogen design vaccine strategies? A Structural biologist’s perspective. Cold Spring Harb. Perspect. Biol. 2017; 9 (11): a029470. Doi:10.1101 / cshperspect.a029470.

12. Visciano M.L., Tuen M., Gorny M.K., Hioe C.E. In vivo alteration of humoral responses to HIV-1 envelope glycoprotein gp120 by antibodies to the CD4-binding site of gp120. Virology. 2008; 372(2): 409–420. Doi:10.1016/j.virol.2007.10.044.

13. Pugach P., Ozorowski G., Cupo A. et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J. Virol. 2015; 89(6): 3380–3395. Doi:10.1128/JVI.03473-14.

14. Jones A.T., Chamcha V., Kesavardhana S. et al. A trimeric HIV-1 envelope gp120 immunogen induces potent and broad anti-V1V2 loop antibodies against HIV-1 in rabbits and rhesus macaques. J. Virol. 2018; 92(5): e01796-17. Doi:10.1128/JVI.01796-17.

15. Vzorov A.N., Wang L., Chen J. et al. Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines. Virology. 2016; 489:141–150. Doi:10.1016/j.virol.2015.09.015.

16. Vzorov A.N., Compans R.W. VLP vaccines and effects of HIV-1 Env protein modifications on their antigenic properties. Mol. Biol. 2016; 50(3): 353–361. Doi:10.1134/S0026893316030110.

17. Vzorov A.N., Compans R.W. Cytoplasmic domain effects on exposure of co-receptor-binding sites of HIV-1 Env. Arch Virol 2016; 161(11): 3011–3018. Doi:10.1007/s00705-016-2998-1.

18. Vzorov A.N., Compans R.W. Effects of stabilization of the gp41 cytoplasmic domain on fusion activity and infectivity of SIVmac239. AIDS Res. Hum. Retroviruses 2011; 27(11): 1213–1222. Doi:10.1089/AID.2010.0321.

19. Vzorov A.N., Bukrinsky M.I., Grigoriev V.B. et al. Highly immunogenic human immunodeficiency viruslike particles are produced by recombinant vaccinia virus-infected cells. AIDS Res. Hum. Retroviruses. 1991; 7(1): 29–36. Doi:10.1089/aid.1991.7.29.

20. Vzorov A.N., Tentsov Yu.Yu., Grigor’ev V.B. et al. Formation of virus-like particles by HIV-1 Gag proteins, expressed by a recombinant vaccinia virus. Mol. Biol. 1990; 24(6): 1666–1674. (In Russ.)

21. Vassilieva E.V., Wang B.Z., Vzorov A.N. et al. Enhanced mucosal immune responses to HIV virus-like particles containing a membrane-anchored adjuvant. MBio. 2011; 2(1): e00328-10. Doi:10.1128/mBio.00328-10.

22. Skountzou I., Quan F.S., Gangadhara S. et al. Incorporation of glycosylphosphatidylinositol-anchored granulocyte-macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles. J. Virol. 2007; 81(3): 1083–1094. Doi:10.1128/JVI.01692-06.

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