Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV.
Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV.
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免疫途径定义了疫苗介导的对SIV的保护的多种机制。
DOI：
10.1038/s41591-018-0161-0
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发表时间：
2018-10
期刊：
影响因子：
82.9
通讯作者：
Alter G
中科院分区：
文献类型：
--
作者：
Ackerman ME;Das J;Pittala S;Broge T;Linde C;Suscovich TJ;Brown EP;Bradley T;Natarajan H;Lin S;Sassic JK;O'Keefe S;Mehta N;Goodman D;Sips M;Weiner JA;Tomaras GD;Haynes BF;Lauffenburger DA;Bailey-Kellogg C;Roederer M;Alter G
抗体是大多数许可疫苗的主要保护相关物;然而，它们的保护机制可能不同，从物理阻断到通过募集先天免疫清除。在这里，我们发现了由免疫位点驱动的疫苗诱导抗体的惊人功能多样性，并与非人灵长类动物中SIV感染风险降低相关。虽然在肌内（IM）和气雾剂（AE）免疫后观察到同等水平的保护，但在其他方面相同的DNA初免，Ad 5加强方案，降低感染风险与IM疫苗接种者中IgG驱动的抗体依赖性单核细胞介导的吞噬作用有关，但在AE免疫动物中通过疫苗引发的IgA驱动的嗜中性粒细胞介导的吞噬作用。因此，虽然途径独立的相关性表明吞噬Fc效应子活性在保护免受SIV中的关键作用，但免疫位点可通过不同的先天效应子细胞和抗体同种型驱动该Fc活性。此外，在第二次非人灵长类动物疫苗试验中，使用不同的IM金丝雀痘初免、蛋白加强策略，与第一次中度保护性人HIV疫苗试验中使用的策略类似，同样与预测的SHIV感染保护相关。这些数据确定了正交功能体液机制，启动不同的疫苗接种途径和免疫策略，指向多个，潜在的互补免疫相关性，可能支持针对HIV的保护性疫苗的合理设计。
Antibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies driven by immunization site and associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization with an otherwise identical DNA prime, Ad5 boost regimen, reduced risk of infection was associated with IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, but via vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE immunized animals. Thus, while route-independent correlates indicate a critical role for phagocytic Fc-effector activity in protection from SIV, the site of immunization may drive this Fc-activity via distinct innate effector cells and antibody isotypes. Moreover, the same correlates predicted protection from SHIV infection in a second non-human primate vaccine trial using a disparate IM canarypox prime, protein boost strategy, analogous to that used in the first moderately protective human HIV vaccine trial. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes and immunization strategies, pointing to multiple, potentially complementary correlates of immunity that may support the rational design of a protective vaccine against HIV.
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影响因子：
82.9
作者：
Fischer, Will;Perkins, Simon;Korber, Bette T.
通讯作者：
Korber, Bette T.
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH
影响因子：
6.7
作者：
Alpert MD;Harvey JD;Lauer WA;Reeves RK;Piatak M Jr;Carville A;Mansfield KG;Lifson JD;Li W;Desrosiers RC;Johnson RP;Evans DT
通讯作者：
Evans DT
影响因子：
2.2
作者：
Gómez-Román, VR;Florese, RH;Robert-Guroff, M
通讯作者：
Robert-Guroff, M
影响因子：
16.6
作者：
Bradley T;Pollara J;Santra S;Vandergrift N;Pittala S;Bailey-Kellogg C;Shen X;Parks R;Goodman D;Eaton A;Balachandran H;Mach LV;Saunders KO;Weiner JA;Scearce R;Sutherland LL;Phogat S;Tartaglia J;Reed SG;Hu SL;Theis JF;Pinter A;Montefiori DC;Kepler TB;Peachman KK;Rao M;Michael NL;Suscovich TJ;Alter G;Ackerman ME;Moody MA;Liao HX;Tomaras G;Ferrari G;Korber BT;Haynes BF
通讯作者：
Haynes BF