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

被引：41

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

来源：

CELL REPORTS | 2020年 / 31卷 / 06期

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.

引用

页数：22

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