title: Vaccination against heterologous R5 clade C SHIV: prevention of infection and correlates of protection.
abstract: A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Lakhashe
authors.forename: Wendy
authors.initials: W
authors.lastname: Wang
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Girish
authors.initials: G
authors.lastname: Hemashettar
authors.forename: Patricia
authors.initials: P
authors.lastname: Polacino
authors.forename: Shiu-Lok
authors.initials: SL
authors.lastname: Hu
authors.forename: François
authors.initials: F
authors.lastname: Villinger
authors.forename: James G
authors.initials: JG
authors.lastname: Else
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Novembre
authors.forename: John K
authors.initials: JK
authors.lastname: Yoon
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
mesh_terms: D000818:Animals; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D015685:Fusion Proteins, gag-pol; D019302:HIV Envelope Protein gp160; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C514797:gp160 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus