Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Abstract

Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)–SIV, DNA–SIV and Ad26–SIV vaccine prime modalities together with two ALVAC–SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16 monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Study design and differences in monocytes in the DNA and Ad26 group.
Fig. 2: Differential contribution of monocytes to protection.
Fig. 3: Monocytes cross-talk with CD4+ T cells and NK cells.
Fig. 4: TH2 cells are associated with NKp44+ cells and antibody response to V2.
Fig. 5: Monocyte markers of protection identified in the present study are associated with the number of SIV challenges to infection in previous studies with ALVAC–SIV or gp96 SIV prime.
Fig. 6

References

  1. 1.

    Pitisuttithum, P. 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. 194, 1661–1671 (2006).

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Gray, G. E. 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. 11, 507–515 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. 3.

    Buchbinder, S. P. 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 372, 1881–1893 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. 4.

    Hammer, S. M. et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N. Engl. J. Med. 369, 2083–2092 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 5.

    Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).

    Article  PubMed  CAS  Google Scholar 

  6. 6.

    Haynes, B. F. et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366, 1275–1286 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Zolla-Pazner, S. et al. Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS ONE 9, e87572 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. 8.

    Lin, L. et al. COMPASS identifies T-cell subsets correlated with clinical outcomes. Nat. Biotechnol. 33, 610–616 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. 9.

    Tomaras, G. D. et al. Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proc. Natl Acad. Sci. USA 110, 9019–9024 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Vaccari, M. et al. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. Nat. Med. 22, 762–770 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. 11.

    Vaccari, M. et al. Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency. J. Virol. 82, 9629–9638 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.

    Baden, L. R. et al. Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans. J. Infect. Dis. 211, 518–528 (2015).

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    Shi, L. Z. et al. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208, 1367–1376 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 14.

    Winning, S. & Fandrey, J. Dendritic cells under hypoxia: how oxygen shortage affects the linkage between innate and adaptive immunity. J. Immunol. Res. 2016, 5134329 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. 15.

    Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10, 417–426 (2002).

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Strbo, N. et al. Cutting edge: novel vaccination modality provides significant protection against mucosal infection by highly pathogenic simian immunodeficiency virus. J. Immunol. 190, 2495–2499 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. 17.

    Pegu, P. et al. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIVmac251 acquisition in an immunization regimen that mimics the RV-144 Thai trial. J. Virol. 87, 1708–1719 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. 18.

    Shi, C. & Pamer, E. G. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11, 762–774 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. 19.

    Carr, M. W. et al. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc. Natl Acad. Sci. USA 91, 3652–3656 (1994).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. 20.

    Yago, T. et al. IL-23 and Th17 disease in inflammatory arthritis. J. Clin. Med. 6, 81 (2017).

  21. 21.

    Chong, S. Z. et al. CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses. J. Exp. Med. 213, 2293–2314 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. 22.

    Bao, W. et al. Sodium salicylate modulates inflammatory responses through AMP-activated protein kinase activation in LPS-stimulated THP-1 cells. J. Cell. Biochem. 119, 850-860 (2018).

  23. 23.

    Chung, Y. H., Kim, D. H. & Lee, W. W. Monosodium urate crystal-induced pro-interleukin-1β production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes. Sci. Rep. 6, 34533 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 24.

    Fan, S. et al. The eIF4E/eIF4G interaction inhibitor 4EGI-1 augments TRAIL-mediated apoptosis through c-FLIP down-regulation and DR5 induction independent of inhibition of cap-dependent protein translation. Neoplasia 12, 346–356 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. 25.

    Kung, C. P. & Raab-Traub, N. Epstein–Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor through effects on Bcl-3 and STAT3. J. Virol. 82, 5486–5493 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. 26.

    Kwissa, M. et al. Dengue virus infection induces expansion of a CD14+CD16+ monocyte population that stimulates plasmablast differentiation. Cell Host Microbe 16, 115–127 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. 27.

    Ludtke, A. et al. Ebola virus disease is characterized by poor activation and reduced levels of circulating CD16+ monocytes. J. Infect. Dis. 214, S275–S280 (2016).

    Article  PubMed  CAS  Google Scholar 

  28. 28.

    Yu, Q. 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 24, 6376–6391 (2006).

    Article  PubMed  CAS  Google Scholar 

  29. 29.

    Ignatius, R. et al. Canarypox virus–induced maturation of dendritic cells is mediated by apoptotic cell death and tumor necrosis factor alpha secretion. J. Virol. 74, 11329–11338 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. 30.

    Fernandes-Alnemri, T. et al. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509–513 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 31.

    Muruve, D. A. et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103–107 (2008).

    Article  PubMed  CAS  Google Scholar 

  32. 32.

    Rao, S. P. et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS ONE 7, e39416 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 33.

    Rivino, L. et al. Chemokine receptor expression identifies pre-T helper (Th)1, pre-Th2, and nonpolarized cells among human CD4+ central memory T cells. J. Exp. Med. 200, 725–735 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. 34.

    Auclair, S. L. et al. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathog. 14, e1006888 (2018).

  35. 35.

    Wei, G. et al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30, 155–167 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. 36.

    Rossol, M. et al. The CD14brightCD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum. 64, 671–677 (2012).

    Article  PubMed  CAS  Google Scholar 

  37. 37.

    Zhu, H. et al. CD16+ monocyte subset was enriched and functionally exacerbated in driving T-cell activation and B-cell response in systemic lupus erythematosus. Front. Immunol. 7, 512 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. 38.

    Eisenbarth, S. C. et al. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453, 1122–1126 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. 39.

    Liu, F. 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. 199, 3293–3305 (2017).

    Article  PubMed  CAS  Google Scholar 

  40. 40.

    Suschak, J. J. et al. Identification of Aim2 as a sensor for DNA vaccines. J. Immunol. 194, 630–636 (2015).

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    Teigler, J. E., Iampietro, M. J. & Barouch, D. H. Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys. J. Virol. 86, 9590–9598 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. 42.

    Teigler, J. E. et al. The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vaccinia virus-based vectors MVA and NYVAC in rhesus monkeys. J. Virol. 88, 1809–1814 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. 43.

    Mitroulis, I. et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172, 147–161.e12 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. 44.

    Cheng, S. C. et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345, 1250684 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. 45.

    Netea, M. G. et al. Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. 46.

    Saeed, S. et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345, 1251086 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. 47.

    Ghonime, M. G. et al. Inflammasome priming by lipopolysaccharide is dependent upon ERK signaling and proteasome function. J. Immunol. 192, 3881–3888 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. 48.

    Panchanathan, R., Liu, H. & Choubey, D. Hypoxia primes human normal prostate epithelial cells and cancer cell lines for the NLRP3 and AIM2 inflammasome activation. Oncotarget 7, 28183–28194 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Gu, L. et al. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404, 407–411 (2000).

    Article  PubMed  CAS  Google Scholar 

  50. 50.

    Cecchinato, V. et al. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunol. 1, 279–288 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. 51.

    Fouts, T. R. et al. Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection. Proc. Natl Acad. Sci. USA 112, E992–E999 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. 52.

    Qureshi, H. et al. Low-dose penile SIVmac251 exposure of rhesus macaques infected with adenovirus type 5 (Ad5) and then immunized with a replication-defective Ad5-based SIV gag/pol/nef vaccine recapitulates the results of the phase IIb step trial of a similar HIV-1 vaccine. J. Virol. 86, 2239–2250 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. 53.

    Reinhardt-Heller, K. et al. Increase of intermediate monocytes in graft-versus-host disease: correlation with MDR1+ Th17.1 levels and the effect of prednisolone and 1α,25-dihydroxyvitamin D3. Biol. Blood Marrow Transplant. 23, 2057–2064 (2017).

    Article  PubMed  CAS  Google Scholar 

  54. 54.

    Joubert, P. E. et al. Autophagy induction by the pathogen receptor CD46. Cell Host Microbe 6, 354–366 (2009).

    Article  PubMed  CAS  Google Scholar 

  55. 55.

    Rodriguez-Rocha, H. et al. Adenoviruses induce autophagy to promote virus replication and oncolysis. Virology 416, 9–15 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. 56.

    Shi, C. S. et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol. 13, 255–263 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. 57.

    Byrne, B. G. et al. Inflammasome components coordinate autophagy and pyroptosis as macrophage responses to infection. mBio 4, e00620-12 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. 58.

    Barouch, D. H. et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482, 89–93 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. 59.

    Strickland, S. L. et al. Significant genetic heterogeneity of the SIVmac251 viral swarm derived from different sources. AIDS Res. Hum. Retroviruses 27, 1327–1332 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Stott, E. J. Anti-cell antibody in macaques. Nature 353, 393 (1991).

    Article  PubMed  CAS  Google Scholar 

  61. 61.

    Barouch, D. H. et al. Characterization of humoral and cellular immune responses elicited by a recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001). J. Infect. Dis. 207, 248–256 (2013).

    Article  PubMed  CAS  Google Scholar 

  62. 62.

    Rosati, M. et al. Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine 26, 5223–5229 (2008).

    Article  PubMed  CAS  Google Scholar 

  63. 63.

    Keele, B. F. et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl Acad. Sci. USA 105, 7552–7557 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Keele, B. F. et al. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J. Exp. Med. 206, 1117–1134 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. 65.

    Romano, J. W. et al. NASBA technology: isothermal RNA amplification in qualitative and quantitative diagnostics. Immunol. Invest. 26, 15–28 (1997).

    Article  PubMed  CAS  Google Scholar 

  66. 66.

    Vaccari, M. et al. Vaccine-induced CD8+ central memory T cells in protection from simian AIDS. J. Immunol. 175, 3502–3507 (2005).

    Article  PubMed  CAS  Google Scholar 

  67. 67.

    Schiffner, T. et al. Immune focusing and enhanced neutralization induced by HIV-1 gp140 chemical cross-linking. J. Virol. 87, 10163–10172 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. 68.

    Li, M. et al. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 79, 10108–10125 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. 69.

    Autissier, P., Soulas, C., Burdo, T. H. & Williams, K. C. Immunophenotyping of lymphocyte, monocyte and dendritic cell subsets in normal rhesus macaques by 12-color flow cytometry: clarification on DC heterogeneity. J. Immunol. Methods 360, 119–128 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. 70.

    Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. 71.

    Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. 72.

    Nakaya, H. I. et al. Systems biology of vaccination for seasonal influenza in humans. Nat. Immunol. 12, 786–795 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. 73.

    Gundem, G. & Lopez-Bigas, N. Sample-level enrichment analysis unravels shared stress phenotypes among multiple cancer types. Genome Med. 4, 28 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Montojo, J. et al. GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics 26, 2927–2928 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. 75.

    Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Ahern for editorial and graphical support and all of the staff at Advanced BioScience Laboratories for helping with the execution of the animal study. We thank J. Lucas, J. Peel and Y. Lin for specific binding and total antibody assays and G. Overman and N. Yates for assay and technical assistance. We thank D. Barouch (Harvard Medical School) for providing the Ad26–SIV recombinant vaccine. This work was mostly supported with federal funds from the intramural program of the National Cancer Institute, NIH, including contract no. HHSN261200800001E (G.F.). Contributions were made by the extramural NIAID program (HHSN27201100016C; D.M.), the Henry M. Jackson Foundation, the US Department of Defense and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325 (R.A.K.) and OPP1147555 (R.A.K.) from the Bill and Melinda Gates Foundation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

Author information

Affiliations

Authors

Contributions

G.F. designed and coordinated the study with M.V. and S.N.G., interpreted the data and wrote the manuscript. S.F. and R.P.S. analyzed the gene expression data, performed the correlates of risk analyses, prepared the figures and helped to write the manuscript. D.R.B. performed the flow cytometry for monocytes in the blood. M.V. performed the studies on TH cell types and analyzed the antibody data and prepared some of the figures together with S.N.G. M.B., L.S., I.S.d.C. M.N.D. performed the analysis of cytokines in the serum. V.G., M.O. and D.F. performed the PCR analysis and RNA extraction. G.G. and N.P.M.L. measured the serum IgG titers and NK cells in the mucosa. H.V.T. and M. Rao measured and analyzed responses to cyclic V2. K.M.M. helped with sorting of monocytes. K.E.F., M. Roederer and R.A.K. performed the intracellular cytokine analysis. B.F.K. measured the number of transmitted variants. X.S., G.D.T., M.P.W., K.J.M., J.S.G., D.N.F., D.C.M. and M. Rosati studied humoral responses in the serum. D.J.V. assisted with statistical analyses. B.K.F., M. Rosati and G.N.P. provided the SIV DNAs.

Corresponding author

Correspondence to Genoveffa Franchini.

Ethics declarations

Competing interests

The US Government in conjunction with Sanofi Pasteur holds Patent 5766598: A Recombinant Attenuated ALVAC Canarypox virus Expression Vectors Containing Heterologous DNA Segments Encoding Lentiviral Gene, inventors E. Paoletti, J. Tartaglia and W. I. Cox, issued 16 June 1998, for the ALVAC vaccine. The US Government also holds Patent 7094408: Improved Immunogenicity Using a Combination of DNA and Vaccinia Virus Vector Vaccines, inventors G. Franchini, Z. Hel and G. Pavlakis, issued 22 August 2006. This patent is for the combination DNA and ALVAC poxvirus vaccines.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 and Supplementary Tables 1 and 4–6

Reporting Summary

Supplementary Table 2

Genes associated with protection from SIVmac251 acquisition

Supplementary Table 3

Immune markers associated with the risk of SIVmac251 acquisition

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vaccari, M., Fourati, S., Gordon, S.N. 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 24, 847–856 (2018). https://doi.org/10.1038/s41591-018-0025-7

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing