Human T-cell lymphotropic virus type 1 (HTLV-1) causes cancer and neuropathology whereas human immunodeficiency virus (HIV)causes AIDS. We uncovered the mechanisms used by HTLV-1 to inhibit innate and adaptive host responses and that HTLV-1 replication in vivo depends on infection of monocytes that necessitate cleavage of the viral p12 precursor protein, thus providing a novel viral therapeutic target. We engineered vaccines, together with the private sector to prevent HTLV-1 and HIV infection. One of the HIV vaccines, the ALVAC-HIV/gp120, has been the first to demonstrate limited, but significant protection against HIV acquisition in humans. Our studies in macaques mirror the human results providing the opportunity to identify the immunological effector(s) of protection and improve vaccine efficacy against HIV.
- Van Prooyen N, Gold H, Andresen V, Schwartz O, Jones K, Ruscetti F, Lockett S, Gudla P, Venzon D, Franchini G. Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission. Proc Natl Acad Sci U S A. 2010;107(48):20738-43.
- Edghill-Smith Y, Golding H, Manischewitz J, King LR, Scott D, Bray M, Nalca A, Hooper JW, Whitehouse CA, Schmitz JE, Reimann KA, Franchini G. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med. 2005;11(7):740-7.
- Nicot C, Dundr M, Johnson JM, Fullen JR, Alonzo N, Fukumoto R, Princler GL, Derse D, Misteli T, Franchini G. HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication. Nat Med. 2004;10(2):197-201.
- Hel Z, Venzon D, Poudyal M, Tsai WP, Giuliani L, Woodward R, Chougnet C, Shearer G, Altman JD, Watkins D, Bischofberger N, Abimiku A, Markham P, Tartaglia J, Franchini G. Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques. Nat Med. 2000;6(10):1140-6.
- Vaccari M, Gordon SN, Fourati S, Schifanella L, Liyanage NP, Cameron M, Keele BF, Shen X, Tomaras GD, Billings E, Rao M, Chung AW, Dowell KG, Bailey-Kellogg C, Brown EP, Ackerman ME, Vargas-Inchaustegui DA, Whitney S, Doster MN, Binello N, Pegu P, Montefiori DC, Foulds K, Quinn DS, Donaldson M, Liang F, Loré K, Roederer M, Koup RA, McDermott A, Ma ZM, Miller CJ, Phan TB, Forthal DN, Blackburn M, Caccuri F, Bissa M, Ferrari G, Kalyanaraman V, Ferrari MG, Thompson D, Robert-Guroff M, Ratto-Kim S, Kim JH, Michael NL, Phogat S, Barnett SW, Tartaglia J, Venzon D, Stablein DM, Alter G, Sekaly RP, Franchini G. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition. Nat Med. 2016;22(7):762-70.
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