Abstract
The design, development, and testing of a successful HIV-1/AIDS vaccine formula are a continuing endeavor over the last two decades. The contemplation of HIV-1/GP160 (cleaved GP120/GP40) trimer complex ENV spike as a vaccine candidate is a biotechnological challenge due to downstream processing issues such as purification, refolding, and conformational stability. The production and reconstitution of protein subunits to form the trimer spike complex for effective immunity triggered by structural conformation are both a protein folding and a protein-protein interaction problem. An effective HIV-1/GP160 (cleaved GP120/GP40) trimer ENV spike complex has nine interfaces with three different types between GP120/GP120, GP40/GP40, and GP120/GP40. This complex protein assembly of recombinant protein subunits is critical for creating a viable immune response in the context of HIV-1/AIDS. The development of an effective vaccine candidate is further obscured by high mutations across different clades in addition to protein glycosylation of the ENV complex. These observations provide valuable insight in the understanding of HIV-1/GP160 (cleaved GP120/GP40) trimer ENV spike complex toward the development of a workable recombinant vaccine candidate.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adis International Ltd (2003) HIV gp120 vaccine—VaxGen: AIDSVAX, AIDSVAX B/B, AIDSVAX B/E, HIV gp120 vaccine—Genentech, HIV gp120 vaccine AIDSVAX—VaxGen, HIV vaccine AIDSVAX—VaxGen. Drugs R D 4(4):249–253
AlSalmi W, Mahalingam M, Ananthaswamy N, Hamlin C, Flores D, Gao G et al (2015) A new approach to produce HIV-1 envelope trimers: both cleavage and proper glycosylation are essential to generate authentic trimers. J Biol Chem 290(32):19780–19795
Bradley T, Fera D, Bhiman J, Eslamizar L, Lu X, Anasti K et al (2016) Structural constraints of vaccine-induced Tier-2 autologous HIV neutralizing antibodies targeting the receptor-binding site. Cell Rep 14(1):43–54
Cicala C, Nawaz F, Jelicic K, Arthos J, Fauci AS (2016) HIV-1 gp120: a target for therapeutics and vaccine design. Curr Drug Targets 17(1):122–135
de Taeye SW, Moore JP, Sanders RW (2016) HIV-1 envelope trimer design and immunization strategies to induce broadly neutralizing antibodies. Trends Immunol 37(3):221–232
Doores KJ (2015) The HIV glycans shield as a target for broadly neutralizing antibodies. FEBS J 282(24):4679–4691
Go EP, Cupo A, Ringe R, Pugach P, Moore JP, Desaire H (2016) Native conformation and canonical disulfide bond formation are interlinked properties of HIV-1 Env glycoproteins. J Virol 90(6):2884–2894
Huang Y, DiazGranados C, Janes H, Huang Y, deCamp AC, Metch B et al (2016) Selection of HIV vaccine candidates for concurrent testing in an efficacy trial. Curr Opin Virol 17:57–65
Kangueane P, Nilofer C (2018) Protein–protein and domain–domain interaction. Springer Nature, New York, pp 1–207 ISBN: 978-981-10-7346-5, 207
Kangueane P, Kayathri R, Sakharkar MK, Flower DR, Sadler K, Chiappelli F (2008) Designing HIV gp120 peptide vaccines: rhetoric or reality for neuro-AIDS. The spectrum of neuro-AIDS disorders: pathophysiology, diagnosis, and treatment. p 105–119
Liu Y, Pan J, Cai Y, Grigorieff N, Harrison SC, Chen B (2017) Conformational states of a soluble, uncleaved HIV-1 envelope trimer. J Virol 91:175–117
Liu CC, Zheng XJ, Ye XS (2016) Broadly neutralizing antibody-guided carbohydrate-based HIV vaccine design: challenges and opportunities. ChemMedChem 11(4):357–362
Nilofer C, Mohanapriya A, Kangueane P (2018) HIV-1 envelope GP160 trimer spike as a vaccine candidate. In: Shapshak P, Levine A, Foley B, Somboonwit C (eds) Global virology II—HIV and neuroaids, 1st edn. Springer-Verlag New York Inc, New York 978-1-4939-7288-3 (ISBN) Chapter 36
Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J et al (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514(7523):455–461
Ringe RP, Yasmeen A, Ozorowski G, Go EP, Pritchard LK, Guttman M et al (2015) Influences on the design and purification of soluble, recombinant native-like HIV-1 envelope glycoprotein trimers. J Virol 89(23):12189–12210
Rerks-Ngarm S, Paris RM, Chunsutthiwat S, Premsri N, Namwat C, Bowonwatanuwong C et al (2013) Extended evaluation of the virologic, immunologic, and clinical course of volunteers who acquired HIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX B/E. J Infect Dis 207(8):1195–1205
Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R et al (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361(23):2209–2220
Sanders RW, Moore JP (2017) Native-like Env trimers as a platform for HIV-1 vaccine design. Immunol Rev 275(1):161–182
Shapshak P, Kangueane P, Fujimura RK, Commins D, Chiappelli F, Singer E et al (2011) Editorial neuroAIDS review. AIDS 25(2):123–141
Shin SY (2016) Recent update in HIV vaccine development. Clin Exp Vaccine Res 5(1):6–11
Sowmya G, Shamini G, Anita S, Sakharkar M, Mathura V, Rodriguez H et al (2011) HIV-1 envelope accessible surface and polarity: clade, blood, and brain. Bioinformation 6(2):48–56
Uberla K (2008) HIV vaccine development in the aftermath of the STEP study: re-focus on occult HIV infection? PLoS Pathog 4(8):e1000114
Verkerke HP, Williams JA, Guttman M, Simonich CA, Liang Y, Filipavicius M et al (2016) Epitope-independent purification of native-like envelope trimers from diverse HIV-1 isolates. J Virol 90(20):9471–9482
Ward AB, Wilson IA (2017) The HIV-1 envelope glycoprotein structure: nailing down a moving target. Immunol Rev 275(1):21–32
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Kangueane, P. (2018). HIV-1 GP160 (GP120/GP40) Trimer ENV Spike Protein. In: Bioinformation Discovery. Springer, Cham. https://doi.org/10.1007/978-3-319-95327-4_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-95327-4_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-95326-7
Online ISBN: 978-3-319-95327-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)