TRISPECIFIC BROADLY NEUTRALIZING ANTIBODIES, N6/PGDM1400-10E8V4 DELIVERED BY RECOMBINANT ADENO-ASSOCIATED VIRUS (RAAV8) VECTOR: A NOVEL VACCINE FOR HIV/AIDS INFECTION
Abstract
ABSTRACT
Introduction: Developing a human immunodeficiency virus (HIV) vaccine with excellent efficacy has become a global urgency that must be addressed immediately. However, the highly diversified HIV-1 envelope glycoprotein (Env) proved to be a challenge in generating an effective HIV vaccine and therapy. HIV/AIDS has already become one of the world's major health issues taking its toll on millions of lives each year. Broadly neutralizing antibodies (bnAbs) as the latest therapy shows excellent promise as a novel vaccine to fight the HIV epidemic. Nevertheless, bNAb as an individual therapeutic agent is not potent enough to fight against the diversity of the HIV epitope. Recently, trispecific N6/PGDM1400-10E8v4, a combination of three various bNAbs has been developed and it has been proven to be the most potent therapy developed at present.
Discussion: This literature review yield results that trispecific N6/PGDM1400-10E8v4 was able to neutralize a large margin of 208 HIV-1 strains up to 99% at IC50<1.0 ?g/ml by targeting multiple epitopes at the same time without losing each of its parental antibodies affinity. We particularly highlight the use of rAAV8 to deliver the bNAbs in order to ensure long-term expression and secretion of antibodies in those infected with HIV.
Conclusion: Thus, the potent and breadth neutralizing ability of trispecific N6/PGDM1400-10E8v4, making it an excellent candidate to become the future HIV vaccine.
Keyword: broadly neutralizing antibodies, HIV, rAAV8, trispecific N6/PGDM1400-10E8v4
Downloads
References
1. Gama L, Koup RA. New-generation high-potency and designer antibodies: role in HIV-1 treatment. Annu Rev Med. 2018;69:14.1-14.11.
2. Stephenson KE, Barouch DH. Broadly neutralizing antibodies for HIV eradication. Springer. 2016;13:31–7.
3. Burton DR, Hangartner L. Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu Rev Immunol. 2016;34:635–59.
4. Ferrari G, Haynes BF, Koenig S, Nordstorm JL, Margolis DM, Tomaras GD. Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection. Springer Nat. 2016;15.
5. Cohen MS, Corey L. Broadly neutralizing antibodies to prevent HIV-1. AAAS. 2017;358(6359).
6. Steinhardt JJ, Guenaga J, Turner HL, McKee K, Louder MK, O’Dell S, et al. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity. Nat Commun. 2018 Feb 28;9(1):877.
7. Wang H, Chen X, Wang D, Yao C, Wang Q, Xie J, et al. Epitope-focused immunogens against the CD4-binding site of HIV-1 envelope protein induce neutralizing antibodies against auto- and heterologous viruses. J Biol Chem. 2018;293(3):830–46.
8. Huang J, Kang BH., Ishida E, Zhou T, Griesman T, Sheng Z, et al. Identification of a CD4-binding-site antibody to HIV that evolved near-pan neutralization breadth. Elsevier Inc. 2016;45:1108–21.
9. Julg B, Pegu A, Abbink P, Liu J, Brinkman A, Molloy K, et al. Virological control by the CD4-binding site antibody N6 in SHIV-infected rhesus monkeys. Journal of Virology. 2017;91(16).
10. Sok D, Burton DR. HIV broadly neutralizing antibodies: taking good care of the 98%. Elsevier Inc. 2016;45.
11. Julg B, Tartaglia LJ, Keele BF, Wagh K, Pegu A, Sok D, et al. Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge. Science Translational Medicine. 2017;9.
12. Sok D, Pauthner M, Julian J-P, Saye-Francisco KL, Hsueh J, Briney B, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. PNAS. 2014;111(49):17624–9.
13. Rujas E, Leaman DP, Insauti S, Ortigosa-Pascual L, Zhang L, Zwick MB, et al. Functional optimization of broadly neutralizing HIV-1 antibody 10E8 by promoting membrane interactions. JVI. 2018;92:e02249-17.
14. Wagh K, Seaman MS, Zingg M, Fitzsimons T, Barouch DH, Burton DR, et al. Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections. PLOS Pathogens. 2018;14(3):e1006860.
15. Kwon YD, Georgiev IS, Ofek G, Zhang B, Asokan M, Bailer RT, et al. Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design. JVI. 2016;90(13):5899–914.
16. Xu L, Pegu A, Rao E, Doria-Rose N, Beninga J, McKee K, et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science. 2017;358(6359):85–9.
17. Steinmetz A, Beil C, Lange C, Baurin N, Beninga J, Corvey C, et al. CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications. Taylor & Francis Group. 2016;8(5):867–78.
18. Brady JM, Baltimore D, Balazs AB. Antibody gene transfer with adeno-associated viral vectors as a method for HIV prevention. John Wiley Sons Ltd. 2017;275:324–33.
19. Fuchs SP, Desrosiers RC. Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies. Mol Ther Methods Clin Dev. 2016;3:16068.
20. Hemphill DD, McIlwraith CW, Goodrich LR. Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers. Sci Rep. 2014;4:5861.
21. Gardner MR, Farzan M. Engineering antibody-like inhibitors to prevent and treat HIV-1 infection. Wolters Kluwer Health Inc. 2017;12(3):294–301.
ABOUT THE JOURNAL
