OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.
OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infectedpatients.
Authors: B F Haynes; L P Hale; K J Weinhold; D D Patel; H X Liao; P B Bressler; D M Jones; J F Demarest; K Gebhard-Mitchell; A T Haase; J A Bartlett Journal: J Clin Invest Date: 1999-02 Impact factor: 14.808
Authors: Sallie R Permar; Youyi Fong; Nathan Vandergrift; Genevieve G Fouda; Peter Gilbert; Robert Parks; Frederick H Jaeger; Justin Pollara; Amanda Martelli; Brooke E Liebl; Krissey Lloyd; Nicole L Yates; R Glenn Overman; Xiaoying Shen; Kaylan Whitaker; Haiyan Chen; Jamie Pritchett; Erika Solomon; Emma Friberg; Dawn J Marshall; John F Whitesides; Thaddeus C Gurley; Tarra Von Holle; David R Martinez; Fangping Cai; Amit Kumar; Shi-Mao Xia; Xiaozhi Lu; Raul Louzao; Samantha Wilkes; Saheli Datta; Marcella Sarzotti-Kelsoe; Hua-Xin Liao; Guido Ferrari; S Munir Alam; David C Montefiori; Thomas N Denny; M Anthony Moody; Georgia D Tomaras; Feng Gao; Barton F Haynes Journal: J Clin Invest Date: 2015-06-08 Impact factor: 14.808
Authors: V Novitsky; N Rybak; M F McLane; P Gilbert; P Chigwedere; I Klein; S Gaolekwe; S Y Chang; T Peter; I Thior; T Ndung'u; F Vannberg; B T Foley; R Marlink; T H Lee; M Essex Journal: J Virol Date: 2001-10 Impact factor: 5.103
Authors: David R Martinez; Nathan Vandergrift; Ayooluwa O Douglas; Erin McGuire; John Bainbridge; Nathan I Nicely; David C Montefiori; Georgia D Tomaras; Genevieve G Fouda; Sallie R Permar Journal: J Virol Date: 2017-04-13 Impact factor: 5.103
Authors: Charmaine P Mutucumarana; Joshua Eudailey; Erin P McGuire; Nathan Vandergrift; Gerald Tegha; Charles Chasela; Sascha Ellington; Charles van der Horst; Athena P Kourtis; Sallie R Permar; Genevieve G Fouda Journal: Clin Vaccine Immunol Date: 2017-08-04
Authors: Barney S Graham; M Juliana McElrath; Michael C Keefer; Kyle Rybczyk; David Berger; Kent J Weinhold; Janet Ottinger; Guido Ferarri; David C Montefiori; Don Stablein; Carol Smith; Richard Ginsberg; John Eldridge; Ann Duerr; Pat Fast; Barton F Haynes Journal: PLoS One Date: 2010-08-10 Impact factor: 3.240
Authors: Jay A Berzofsky; Jeffrey D Ahlers; John Janik; John Morris; SangKon Oh; Masaki Terabe; Igor M Belyakov Journal: J Clin Invest Date: 2004-08 Impact factor: 14.808