ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

English version

Autoři: Luca Schifanella ^aff001; Susan W. Barnett ^aff002; Massimiliano Bissa ^aff001; Veronica Galli ^aff001; Melvin N. Doster ^aff001; Monica Vaccari ^aff001; Georgia D. Tomaras ^aff003; Xiaoying Shen ^aff003; Sanjay Phogat ^aff004; Ranajit Pal ^aff005; David C. Montefiori ^aff003; Celia C. LaBranche ^aff003; Mangala Rao ^aff006; Hung V. Trinh ^aff006; Robyn Washington-Parks ^aff001; Namal P. M. Liyanage ^aff001; Dallas R. Brown ^aff001; Frank Liang ^aff008; Karin Loré ^aff008; David J. Venzon ^aff009; William Magnanelli ^aff010; Michelle Metrinko ^aff010; Josh Kramer ^aff010; Matthew Breed ^aff010; Galit Alter ^aff011; Ruth M. Ruprecht ^aff012; Genoveffa Franchini ^aff001
Působiště autorů: Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America ^aff001; Novartis Vaccines and Diagnostics, Inc, Cambridge, Massachusetts, United States of America ^aff002; Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America ^aff003; Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America ^aff004; Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America ^aff005; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America ^aff006; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America ^aff007; Karolinska Institute, Stockholm, Sweden ^aff008; Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America ^aff009; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States of America ^aff010; Ragon Institute of MGH, MIT, and Harvard Cambridge, Boston, Massachusetts, United States of America ^aff011; Texas Biomedical Research Institute, San Antonio, Texas, United States of America ^aff012
Vyšlo v časopise: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008121
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1008121

Souhrn

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Klíčová slova:

Blood plasma – Vaccines – Antibodies – Immunologic adjuvants – Macaque – Rhesus monkeys – Alumni

Zdroje

1. IAVI. Clinical Trial Database: International AIDS Vaccine Initiative; 2019. Available from: https://www.iavi.org/trials-database.

2. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372(9653):1881–93. doi: 10.1016/S0140-6736(08)61591-3 19012954; PubMed Central PMCID: PMC2721012.

3. Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, et al. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 2011;11(7):507–15. Epub 2011/05/17. doi: 10.1016/S1473-3099(11)70098-6 21570355; PubMed Central PMCID: PMC3417349.

4. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013;369(22):2083–92. Epub 2013/10/09. doi: 10.1056/NEJMoa1310566 24099601; PubMed Central PMCID: PMC4030634.

5. Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194(12):1661–71. doi: 10.1086/508748 17109337.

6. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. The New England journal of medicine. 2009;361(23):2209–20. doi: 10.1056/NEJMoa0908492 19843557.

7. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. The New England journal of medicine. 2012;366(14):1275–86. doi: 10.1056/NEJMoa1113425 22475592; PubMed Central PMCID: PMC3371689.

8. Rolland M, Edlefsen PT, Larsen BB, Tovanabutra S, Sanders-Buell E, Hertz T, et al. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2. Nature. 2012;490(7420):417–20. doi: 10.1038/nature11519 22960785; PubMed Central PMCID: PMC3551291.

9. WHO. Data and Statistics. 2015.

10. Hemelaar J, Gouws E, Ghys PD, Osmanov S, Isolation W-UNfH, Characterisation. Global trends in molecular epidemiology of HIV-1 during 2000–2007. AIDS. 2011;25(5):679–89. doi: 10.1097/QAD.0b013e328342ff93 21297424; PubMed Central PMCID: PMC3755761.

11. clinicaltrials.gov. Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa (HVTN702). clinicaltrialsgov. 2016.

12. Bekker LG, Moodie Z, Grunenberg N, Laher F, Tomaras GD, Cohen KW, et al. Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial. Lancet HIV. 2018;5(7):e366–e78. Epub 2018/06/15. doi: 10.1016/S2352-3018(18)30071-7 29898870; PubMed Central PMCID: PMC6028742.

13. Avert. HIV and AIDS in South Africa 2016. Available from: https://www.avert.org/professionals/hiv-around-world/sub-saharan-africa/south-africa.

14. UNAIDS. Ending AIDS: Progress towards 90-90-90 targets2017 2018. Available from: http://www.unaids.org/sites/default/files/media_asset/Global_AIDS_update_2017_en.pdf.

15. UNAIDS. Thailand 2016 Country Factsheet2017 2018. Available from: http://www.unaids.org/en/regionscountries/countries/thailand.

16. Avert. HIV and AIDS in Thailand 2016. Available from: https://www.avert.org/professionals/hiv-around-world/asia-pacific/thailand.

17. Vaccari M, Fourati S, Gordon SN, Brown DR, Bissa M, Schifanella L, et al. HIV vaccine candidate activation of hypoxia and the inflammasome in CD14(+) monocytes is associated with a decreased risk of SIVmac251 acquisition. Nat Med. 2018. Epub 2018/05/23. doi: 10.1038/s41591-018-0025-7 29785023.

18. Vaccari M, Gordon SN, Fourati S, Schifanella L, Liyanage NP, Cameron M, et al. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. Nat Med. 2016;22(7):762–70. doi: 10.1038/nm.4105 27239761.

19. Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, et al. Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy. Science. 2016;354(6309):197–202. doi: 10.1126/science.aag1276 27738167; PubMed Central PMCID: PMC5405455.

20. Song RJ, Chenine AL, Rasmussen RA, Ruprecht CR, Mirshahidi S, Grisson RD, et al. Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env. Journal of virology. 2006;80(17):8729–38. Epub 2006/08/17. doi: 10.1128/JVI.00558-06 16912320; PubMed Central PMCID: PMC1563858.

21. Tomaras GD, Ferrari G, Shen X, Alam SM, Liao HX, Pollara J, et al. Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(22):9019–24. doi: 10.1073/pnas.1301456110 23661056; PubMed Central PMCID: PMC3670311.

22. Siddappa NB, Watkins JD, Wassermann KJ, Song R, Wang W, Kramer VG, et al. R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models. PLoS One. 2010;5(7):e11689. Epub 2010/07/27. doi: 10.1371/journal.pone.0011689 20657739; PubMed Central PMCID: PMC2908149.

23. Zolla-Pazner S, Lubeck M, Xu S, Burda S, Natuk RJ, Sinangil F, et al. Induction of neutralizing antibodies to T-cell line-adapted and primary human immunodeficiency virus type 1 isolates with a prime-boost vaccine regimen in chimpanzees. J Virol. 1998;72(2):1052–9. Epub 1998/01/28. 9444999; PubMed Central PMCID: PMC124577.

24. Gomez-Roman VR, Florese RH, Peng B, Montefiori DC, Kalyanaraman VS, Venzon D, et al. An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains. J Acquir Immune Defic Syndr. 2006;43(3):270–7. Epub 2006/08/31. doi: 10.1097/01.qai.0000230318.40170.60 16940858.

25. Tuero I, Mohanram V, Musich T, Miller L, Vargas-Inchaustegui DA, Demberg T, et al. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge. PLoS Pathog. 2015;11(8):e1005101. Epub 2015/08/13. doi: 10.1371/journal.ppat.1005101 26267144; PubMed Central PMCID: PMC4534401.

26. Luster AD, Unkeless JC, Ravetch JV. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985;315(6021):672–6. doi: 10.1038/315672a0 3925348.

27. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27–31. Epub 2016/04/09. doi: 10.4103/0976-0105.177703 27057123; PubMed Central PMCID: PMC4804402.

28. Auclair S, Liu F, Niu Q, Hou W, Churchyard G, Morgan C, et al. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathog. 2018;14(2):e1006888. Epub 2018/02/24. doi: 10.1371/journal.ppat.1006888 29474461; PubMed Central PMCID: PMC5841825.

29. Teigler JE, Phogat S, Franchini G, Hirsch VM, Michael NL, Barouch DH. The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vaccinia virus-based vectors MVA and NYVAC in rhesus monkeys. J Virol. 2014;88(3):1809–14. Epub 2013/11/22. doi: 10.1128/JVI.02386-13 24257612; PubMed Central PMCID: PMC3911591.

30. Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature. 2008;453(7198):1122–6. doi: 10.1038/nature06939 18496530; PubMed Central PMCID: PMC4804622.

31. Yu Q, Jones B, Hu N, Chang H, Ahmad S, Liu J, et al. Comparative analysis of tropism between canarypox (ALVAC) and vaccinia viruses reveals a more restricted and preferential tropism of ALVAC for human cells of the monocytic lineage. Vaccine. 2006;24(40–41):6376–91. doi: 10.1016/j.vaccine.2006.06.011 16859816.

32. Liu F, Niu Q, Fan X, Liu C, Zhang J, Wei Z, et al. Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16-STING-Type I IFN Pathway and AIM2 Sensor. J Immunol. 2017;199(9):3293–305. doi: 10.4049/jimmunol.1700698 28947539; PubMed Central PMCID: PMC5679316.

33. Geretti AM. HIV-1 subtypes: epidemiology and significance for HIV management. Curr Opin Infect Dis. 2006;19(1):1–7. doi: 10.1097/01.qco.0000200293.45532.68 16374210.

34. Robb ML, Rerks-Ngarm S, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Kunasol P, et al. Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144. Lancet Infect Dis. 2012;12(7):531–7. Epub 2012/06/02. doi: 10.1016/S1473-3099(12)70088-9 22652344; PubMed Central PMCID: PMC3530398.

35. Gordon SN, Liyanage NP, Doster MN, Vaccari M, Vargas-Inchaustegui DA, Pegu P, et al. Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition. J Immunol. 2016;197(7):2726–37. Epub 2016/09/04. doi: 10.4049/jimmunol.1600674 27591322; PubMed Central PMCID: PMC5026031.

36. Pegu P, Vaccari M, Gordon S, Keele BF, Doster M, Guan Y, et al. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial. Journal of virology. 2013;87(3):1708–19. doi: 10.1128/JVI.02544-12 23175374; PubMed Central PMCID: PMC3554145.

37. Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine. 2011;29(51):9538–43. Epub 2011/10/18. doi: 10.1016/j.vaccine.2011.09.124 22001122.

38. ATSDR. Toxicological Profiles: Aluminum. Available from: https://www.atsdr.cdc.gov/toxprofiles/tp22-c1.pdf.

39. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, et al. Trained immunity: A program of innate immune memory in health and disease. Science. 2016;352(6284):aaf1098. Epub 2016/04/23. doi: 10.1126/science.aaf1098 27102489; PubMed Central PMCID: PMC5087274.

40. Dugast AS, Arnold K, Lofano G, Moore S, Hoffner M, Simek M, et al. Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV. Clin Infect Dis. 2017;64(8):1098–104. doi: 10.1093/cid/cix057 28158448.

41. Pal R, Venzon D, Santra S, Kalyanaraman VS, Montefiori DC, Hocker L, et al. Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels. Journal of virology. 2006;80(8):3732–42. doi: 10.1128/JVI.80.8.3732-3742.2006 16571790; PubMed Central PMCID: PMC1440474.

42. Romano JW, Williams KG, Shurtliff RN, Ginocchio C, Kaplan M. NASBA technology: isothermal RNA amplification in qualitative and quantitative diagnostics. Immunol Invest. 1997;26(1–2):15–28. doi: 10.3109/08820139709048912 9037609.

43. Vaccari M, Trindade CJ, Venzon D, Zanetti M, Franchini G. Vaccine-induced CD8+ central memory T cells in protection from simian AIDS. J Immunol. 2005;175(6):3502–7. doi: 10.4049/jimmunol.175.6.3502 16148092.

44. Pal R, Venzon D, Letvin NL, Santra S, Montefiori DC, Miller NR, et al. ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency. J Virol. 2002;76(1):292–302. doi: 10.1128/JVI.76.1.292-302.2002 11739694; PubMed Central PMCID: PMC135699.

45. Montefiori DC. Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Curr Protoc Immunol. 2005;Chapter 12:Unit 12 1. Epub 2008/04/25. doi: 10.1002/0471142735.im1211s64 18432938.

46. Schiffner T, Kong L, Duncan CJ, Back JW, Benschop JJ, Shen X, et al. Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J Virol. 2013;87(18):10163–72. Epub 2013/07/12. doi: 10.1128/JVI.01161-13 23843636; PubMed Central PMCID: PMC3754013.

47. Gottardo R, Bailer RT, Korber BT, Gnanakaran S, Phillips J, Shen X, et al. Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PLoS One. 2013;8(9):e75665. Epub 2013/10/03. doi: 10.1371/journal.pone.0075665 24086607; PubMed Central PMCID: PMC3784573.

48. Shen X, Duffy R, Howington R, Cope A, Sadagopal S, Park H, et al. Vaccine-Induced Linear Epitope-Specific Antibodies to Simian Immunodeficiency Virus SIVmac239 Envelope Are Distinct from Those Induced to the Human Immunodeficiency Virus Type 1 Envelope in Nonhuman Primates. Journal of virology. 2015;89(16):8643–50. Epub 2015/05/29. doi: 10.1128/JVI.03635-14 26018159; PubMed Central PMCID: PMC4524233.

49. Singh S, Ramirez-Salazar EG, Doueiri R, Valentin A, Rosati M, Hu X, et al. Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques. J Virol. 2018;92(15). Epub 2018/05/26. doi: 10.1128/JVI.00281-18 29793957; PubMed Central PMCID: PMC6052320.

50. Wen Y, Trinh HV, Linton CE, Tani C, Norais N, Martinez-Guzman D, et al. Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant. PLoS One. 2018;13(4):e0194266. Epub 2018/04/27. doi: 10.1371/journal.pone.0194266 29698406; PubMed Central PMCID: PMC5919662.

51. Ulanova M, Tarkowski A, Hahn-Zoric M, Hanson LA. The Common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun. 2001;69(2):1151–9. Epub 2001/02/13. doi: 10.1128/IAI.69.2.1151-1159.2001 11160013; PubMed Central PMCID: PMC97997.

52. Ackerman ME, Das J, Pittala S, Broge T, Linde C, Suscovich TJ, et al. Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV. Nat Med. 2018;24(10):1590–8. Epub 2018/09/05. doi: 10.1038/s41591-018-0161-0 30177821.