First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine (IPCAVD 001)

被引：135

作者：

Baden, Lindsey R. ^{[1
,3
,4
]}

Walsh, Stephen R. ^{[1
,3
]}

Seaman, Michael S. ^{[2
,3
]}

Tucker, Robert P. ^{[1
]}

Krause, Kathleen H. ^{[1
]}

Patel, Alka ^{[1
]}

Johnson, Jennifer A. ^{[1
,3
]}

Kleinjan, Jane ^{[1
]}

Yanosick, Katherine E. ^{[2
]}

Perry, James ^{[2
]}

Zablowsky, Elise ^{[2
]}

Abbink, Peter ^{[2
]}

Peter, Lauren ^{[2
]}

Iampietro, M. Justin ^{[2
]}

Cheung, Ann ^{[2
]}

Pau, Maria G. ^{[5
]}

Weijtens, Mo ^{[5
]}

Goudsmit, Jaap ^{[5
]}

Swann, Edith ^{[7
]}

Wolff, Mark ^{[6
]}

Loblein, Hayley ^{[6
]}

Dolin, Raphael ^{[2
,3
,4
]}

Barouch, Dan H. ^{[2
,3
,4
]}

机构：

[1] Brigham & Womens Hosp, Rockville, MD USA

[2] Beth Israel Deaconess Med Ctr, Boston, MA USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Ragon Inst MGH MIT & Harvard, Boston, MA USA

[5] Crucell Holland BV, Leiden, Netherlands

[6] EMMES Corp Rockville, Rockville, MD USA

[7] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2013年 / 207卷 / 02期

关键词：

HIV Vaccine; Adenovirus; 26; Safety; Immunogenicity; Dose-escalation; CELLULAR IMMUNE-RESPONSES; RHESUS-MONKEYS; PHASE-1; SAFETY; HEALTHY-ADULTS; VECTORS; TRIAL; INFECTION; TYPE-5; STEP;

D O I：

10.1093/infdis/jis670

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Background. We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans. Methods. Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. Results. Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 x 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively. Conclusion. This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 x 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1.

引用

页码：240 / 247

页数：8

共 28 条

[1]

Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D [J].

Abbink, Peter ;

Lemckert, Angelique A. C. ;

Ewald, Bonnie A. ;

Lynch, Diana M. ;

Denholtz, Matthew ;

Smits, Shirley ;

Holterman, Lennart ;

Damen, Irma ;

Vogels, Ronald ;

Thorner, Anna R. ;

O'Brien, Kara L. ;

Carville, Angela ;

Mansfield, Keith G. ;

Goudsmit, Jaap ;

Havenga, Menzo J. E. ;

Barouch, Dan H. .

JOURNAL OF VIROLOGY, 2007, 81 (09) :4654-4663

[2]

Timing of Plasmid Cytokine (IL-2/Ig) Administration Affects HIV-1 Vaccine Immunogenicity in HIV-Seronegative Subjects [J].

Baden, Lindsey R. ;

Blattner, William A. ;

Morgan, Cecilia ;

Huang, Yunda ;

Defawe, Olivier D. ;

Sobieszczyk, Magdalena E. ;

Kochar, Nidhi ;

Tomaras, Georgia D. ;

McElrath, M. Juliana ;

Russell, Nina ;

Brandariz, Kara ;

Cardinali, Massimo ;

Graham, Barney S. ;

Barouch, Dan H. ;

Dolin, Raphael .

JOURNAL OF INFECTIOUS DISEASES, 2011, 204 (10) :1541-1549

[3]

Characterization of Humoral and Cellular Immune Responses Elicited by a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine in Healthy Adults (IPCAVD 001) [J].

Barouch, Dan H. ;

Liu, Jinyan ;

Peter, Lauren ;

Abbink, Peter ;

Iampietro, M. Justin ;

Cheung, Ann ;

Alter, Galit ;

Chung, Amy ;

Dugast, Anne-Sophie ;

Frahm, Nicole ;

McElrath, M. Juliana ;

Wenschuh, Holger ;

Reimer, Ulf ;

Seaman, Michael S. ;

Pau, Maria G. ;

Weijtens, Mo ;

Goudsmit, Jaap ;

Walsh, Stephen R. ;

Dolin, Raphael ;

Baden, Lindsey R. .

JOURNAL OF INFECTIOUS DISEASES, 2013, 207 (02) :248-256

[4]

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys [J].

Barouch, Dan H. ;

Liu, Jinyan ;

Li, Hualin ;

Maxfield, Lori F. ;

Abbink, Peter ;

Lynch, Diana M. ;

Iampietro, M. Justin ;

SanMiguel, Adam ;

Seaman, Michael S. ;

Ferrari, Guido ;

Forthal, Donald N. ;

Ourmanov, Ilnour ;

Hirsch, Vanessa M. ;

Carville, Angela ;

Mansfield, Keith G. ;

Stablein, Donald ;

Pau, Maria G. ;

Schuitemaker, Hanneke ;

Sadoff, Jerald C. ;

Billings, Erik A. ;

Rao, Mangala ;

Robb, Merlin L. ;

Kim, Jerome H. ;

Marovich, Mary A. ;

Goudsmit, Jaap ;

Michael, Nelson L. .

NATURE, 2012, 482 (7383) :89-U115

[5]

International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations [J].

Barouch, Dan H. ;

Kik, Sandra V. ;

Weverling, Gerrit J. ;

Dilan, Rebecca ;

King, Sharon L. ;

Maxfield, Lori F. ;

Clark, Sarah ;

Ng'ang'a, David ;

Brandariz, Kara L. ;

Abbink, Peter ;

Sinangil, Faruk ;

de Bruyn, Guy ;

Gray, Glenda E. ;

Roux, Surita ;

Bekker, Linda-Gail ;

Dilraj, Athmanundh ;

Kibuuka, Hannah ;

Robb, Merlin L. ;

Michael, Nelson L. ;

Anzala, Omu ;

Amornkul, Pauli N. ;

Gilmour, Jill ;

Hural, John ;

Buchbinder, Susan P. ;

Seaman, Michael S. ;

Dolin, Raphael ;

Baden, Lindsey R. ;

Carville, Angela ;

Mansfield, Keith G. ;

Pau, Maria G. ;

Goudsmit, Jaap .

VACCINE, 2011, 29 (32) :5203-5209

[6]

Novel adenovirus vector-based vaccines for HIV-1 [J].

Barouch, Dan H. .

CURRENT OPINION IN HIV AND AIDS, 2010, 5 (05) :386-390

[7]

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

[8]

EV01:: A phase I trial in healthy HIV negative volunteers to evaluate a clade CHIV vaccine, NYVAC-C undertaken by the EuroVacc Consortium [J].

Bart, Pierre-Alexandre ;

Goodall, Ruth ;

Barber, Tristan ;

Harari, Alexandre ;

Guimaraes-Walker, Ana ;

Khonkarly, Mona ;

Sheppard, Neil C. ;

Bangala, Yolanda ;

Frachette, Marie-Joelle ;

Wagner, Ralf ;

Liljestrom, Peter ;

Kraehenbuhl, Jean-Pierre ;

Girard, Marc ;

Goudsmit, Jaap ;

Esteban, Mariano ;

Heeney, Jonathan ;

Sattentau, Quentin ;

McCormack, Sheena ;

Babiker, Abdel ;

Pantaleo, Giuseppe ;

Weber, Jonathan .

VACCINE, 2008, 26 (25) :3153-3161

[9]

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

[10]

Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector [J].

Catanzaro, Andrew T. ;

Koup, Richard A. ;

Roederer, Mario ;

Bailer, Robert T. ;

Enama, Mary E. ;

Moodie, Zoe ;

Gu, Lin ;

Martin, Julie E. ;

Novik, Laura ;

Chakrabarti, Bimal K. ;

Butman, Bryan T. ;

Gall, Jason G. D. ;

King, C. Richter ;

Andrews, Charla A. ;

Sheets, Rebecca ;

Gomez, Phillip L. ;

Mascola, John R. ;

Nabel, Gary J. ;

Graham, Barney S. .

JOURNAL OF INFECTIOUS DISEASES, 2006, 194 (12) :1638-1649

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