Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge

被引:44
作者
Felber, Barbara K. [1 ]
Lu, Zhongyan [1 ]
Hu, Xintao [1 ]
Valentin, Antonio [2 ]
Rosati, Margherita [2 ]
Remmel, Christopher A. L. [3 ]
Weiner, Joshua A. [3 ]
Carpenter, Margaret C. [3 ]
Faircloth, Katelyn [3 ]
Stanfield-Oakley, Sherry [4 ,5 ,6 ]
Williams, Wilton B. [4 ]
Shen, Xiaoying [4 ]
Tomaras, Georgia D. [4 ,5 ,6 ,7 ]
LaBranche, Celia C. [4 ,5 ]
Montefiori, David [4 ,5 ]
Trinh, Hung, V [8 ,9 ]
Rao, Mangala [8 ]
Alam, Munir S. [4 ]
Vandergrift, Nathan A. [4 ,19 ]
Saunders, Kevin O. [4 ,5 ]
Wang, Yunfei [4 ]
Rountree, Wes [4 ]
Das, Jishnu [10 ]
Alter, Galit [10 ]
Reed, Steven G. [11 ]
Aye, Pyone P. [12 ]
Schiro, Faith [12 ]
Pahar, Bapi [12 ]
Dufour, Jason P. [12 ]
Veazey, Ronald S. [12 ]
Marx, Preston A. [13 ,14 ]
Venzon, David J. [15 ]
Shaw, George M. [16 ,17 ]
Ferrari, Guido [4 ,5 ,6 ]
Ackerman, Margaret E. [3 ]
Haynes, Barton F. [4 ,18 ]
Pavlakis, George N. [2 ]
机构
[1] NCI Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA
[2] NCI Frederick, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA
[3] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA
[4] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA
[5] Duke Univ, Dept Surg, Durham, NC 27710 USA
[6] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[7] Duke Univ, Dept Immunol, Durham, NC 27710 USA
[8] US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA
[9] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA
[10] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA
[11] Infect Dis Res Inst, Seattle, WA 98102 USA
[12] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA
[13] Tulane Univ, Sch Publ Hlth & Trop Med, Tulane Natl Primate Res Ctr, New Orleans, LA 70112 USA
[14] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA 70112 USA
[15] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[16] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[17] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
[18] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[19] RTI Int, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA
基金
美国国家卫生研究院;
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; HIV-1 VACCINE EFFICACY; FUSION INHIBITOR T-20; CHRONIC VIREMIA; CELL RESPONSES; SIV CHALLENGES; ENVELOPE; EPITOPE; TYPE-1;
D O I
10.1016/j.celrep.2020.107624
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to Fc gamma RIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity.
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页数:22
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