Phase 1 Safety and Immunogenicity Testing of DNA and Recombinant Modified Vaccinia Ankara Vaccines Expressing HIV-1 Virus-like Particles

被引:131
作者
Goepfert, Paul A. [1 ]
Elizaga, Marnie L. [2 ]
Sato, Alicia [2 ]
Qin, Li [2 ]
Cardinali, Massimo [4 ]
Hay, Christine M. [6 ]
Hural, John [3 ]
DeRosa, Stephen C. [3 ]
DeFawe, Olivier D. [3 ]
Tomaras, Georgia D. [7 ]
Montefiori, David C. [7 ]
Xu, Yongxian
Lai, Lilin [8 ]
Kalams, Spyros A. [9 ]
Baden, Lindsey R. [10 ]
Frey, Sharon E. [11 ]
Blattner, William A. [5 ]
Wyatt, Linda S. [4 ]
Moss, Bernard [4 ]
Robinson, Harriet L.
机构
[1] Univ Alabama, Dept Med, Birmingham, AL 35294 USA
[2] Fred Hutchinson Canc Res Ctr, Core Operat Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA
[3] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA
[4] NIAID, Bethesda, MD 20892 USA
[5] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA
[6] Univ Rochester, Dept Med, New York, NY USA
[7] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[8] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[9] Vanderbilt Univ, Sch Med, Dept Internal Med, Nashville, TN 37212 USA
[10] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA
[11] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63103 USA
关键词
T-CELL RESPONSES; SIMIAN IMMUNODEFICIENCY; DNA/MVA VACCINE; RHESUS-MONKEYS; TYPE-1; CLADE; MUCOSAL CHALLENGE; IMMUNE-RESPONSES; PLASMID DNA; ALVAC-SIV; ENV;
D O I
10.1093/infdis/jiq105
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Methods. GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants. Results. Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM. Conclusions. MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.
引用
收藏
页码:610 / 619
页数:10
相关论文
共 35 条
[1]   Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine [J].
Amara, RR ;
Villinger, F ;
Altman, JD ;
Lydy, SL ;
O'Neil, SP ;
Staprans, SI ;
Montefiori, DC ;
Xu, Y ;
Herndon, JG ;
Wyatt, LS ;
Candido, MA ;
Kozyr, NL ;
Earl, PL ;
Smith, JM ;
Ma, HL ;
Grimm, BD ;
Hulsey, ML ;
Miller, J ;
McClure, HM ;
McNicholl, JM ;
Moss, B ;
Robinson, HL .
SCIENCE, 2001, 292 (5514) :69-74
[2]   Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines [J].
Amara, RR ;
Villinger, F ;
Staprans, SI ;
Altman, JD ;
Montefiori, DC ;
Kozyr, NL ;
Xu, Y ;
Wyatt, LS ;
Earl, PL ;
Herndon, JG ;
McClure, HM ;
Moss, B ;
Robinson, HL .
JOURNAL OF VIROLOGY, 2002, 76 (15) :7625-7631
[3]   Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys [J].
Barouch, Dan H. ;
O'Brien, Kara L. ;
Simmons, Nathaniel L. ;
King, Sharon L. ;
Abbink, Peter ;
Maxfield, Lori F. ;
Sun, Ying-Hua ;
La Porte, Annalena ;
Riggs, Ambryice M. ;
Lynch, Diana M. ;
Clark, Sarah L. ;
Backus, Katherine ;
Perry, James R. ;
Seaman, Michael S. ;
Carville, Angela ;
Mansfield, Keith G. ;
Szinger, James J. ;
Fischer, Will ;
Muldoon, Mark ;
Korber, Bette .
NATURE MEDICINE, 2010, 16 (03) :319-U116
[4]   Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial [J].
Buchbinder, Susan P. ;
Mehrotra, Devon V. ;
Duerr, Ann ;
Fitzgerald, Daniel W. ;
Mogg, Robin ;
Li, David ;
Gilbert, Peter B. ;
Lama, Javier R. ;
Marmor, Michael ;
del Rio, Carlos ;
McElrath, M. Juliana ;
Casimiro, Danilo R. ;
Gottesdiener, Keith M. ;
Chodakewitz, Jeffrey A. ;
Corey, Lawrence ;
Robertson, Michael N. .
LANCET, 2008, 372 (9653) :1881-1893
[5]   Defining blood processing parameters for optimal detection of cryopreserved antigen-specific responses for HIV vaccine trials [J].
Bull, Marta ;
Lee, Deborah ;
Stucky, Jason ;
Chiu, Ya-Lin ;
Rubin, Abbe ;
Horton, Helen ;
McElrath, M. Juliana .
JOURNAL OF IMMUNOLOGICAL METHODS, 2007, 322 (1-2) :57-69
[6]   HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges [J].
Ellenberger, Dennis ;
Otten, Ronald A. ;
Li, Bin ;
Aidoo, Michael ;
Rodriguez, I. Vanessa ;
Sariol, Carlos A. ;
Martinez, Melween ;
Monsour, Michael ;
Wyatt, Linda ;
Hudgens, Michael G. ;
Edmundo, Kraiselburd ;
Bernard, Moss ;
Robinson, Harriet ;
Thomas, Folks ;
Butera, Salvatore .
VIROLOGY, 2006, 352 (01) :216-225
[7]  
Flynn MN, 2005, J INFECT DIS, V191, P654, DOI 10.1086/428404
[8]   High-dose recombinant canarypox vaccine expressing HIV-1 protein, in seronegative human subjects [J].
Goepfert, PA ;
Horton, H ;
McElrath, MJ ;
Gurunathan, S ;
Ferrari, G ;
Tomaras, GD ;
Montefiori, DC ;
Allen, M ;
Chiu, YL ;
Spearman, P ;
Fuchs, JD ;
Koblin, BA ;
Blattner, WA ;
Frey, S ;
Keefer, MC ;
Baden, LR ;
Corey, L .
JOURNAL OF INFECTIOUS DISEASES, 2005, 192 (07) :1249-1259
[9]   Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction [J].
Hanke, Tomas ;
McMichael, Andrew J. ;
Dorrell, Lucy .
JOURNAL OF GENERAL VIROLOGY, 2007, 88 :1-12
[10]   Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge [J].
Hansen, Scott G. ;
Vieville, Cassandra ;
Whizin, Nathan ;
Coyne-Johnson, Lia ;
Siess, Don C. ;
Drummond, Derek D. ;
Legasse, Alfred W. ;
Axthelm, Michael K. ;
Oswald, Kelli ;
Trubey, Charles M. ;
Piatak, Michael, Jr. ;
Lifson, Jeffrey D. ;
Nelson, Jay A. ;
Jarvis, Michael A. ;
Picker, Louis J. .
NATURE MEDICINE, 2009, 15 (03) :293-299