Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.
Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.
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DOI：
10.1371/journal.ppat.1008764
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发表时间：
2020-09
期刊：
影响因子：
6.7
通讯作者：
Bolton DL
中科院分区：
文献类型：
--
作者：
Om K;Paquin-Proulx D;Montero M;Peachman K;Shen X;Wieczorek L;Beck Z;Weiner JA;Kim D;Li Y;Mdluli T;Shubin Z;Bryant C;Sharma V;Tokarev A;Dawson P;White Y;Appelbe O;Klatt NR;Tovanabutra S;Estes JD;Matyas GR;Ferrari G;Alving CR;Tomaras GD;Ackerman ME;Michael NL;Robb ML;Polonis V;Rolland M;Eller MA;Rao M;Bolton DL
为了使用下一代佐剂增强 HIV-1 痘蛋白疫苗的免疫原性，使用铝（明矾）或吸附到明矾的新型脂质体单磷酰脂质 A (MPLA) 制剂 ALFA 在猕猴中评估了重组改良痘苗病毒 Ankara 和多聚体 Env gp145 的初免-加强策略。各组之间的结合抗体反应强劲且具有可比性，而 ALFA 大大增强了抗体依赖性中性粒细胞和单核细胞吞噬反应。在 ALFA 佐剂的男性中，针对异源 2 级 SHIV 粘膜攻击的每次暴露疫苗功效为 90%（P = 0.002），而明矾没有提供保护。在最后一次疫苗接种后七个月的完整挑战系列后，一半接受 ALFA 佐剂的雄性仍未受到感染。抗体依赖性单核细胞和中性粒细胞的吞噬反应均与保护密切相关。感染风险存在显着的性别差异，女性感染率远低于男性。在人类中，相对于明矾，MPLA-脂质体-明矾佐剂 gp120 也增加了 HIV-1 特异性吞噬反应。因此，下一代基于脂质体的佐剂可以驱动疫苗引发的抗体效应活性，从而在猕猴和人类中产生有效的吞噬反应，并且这些反应与保护相关。未来旨在改善功能性体液反应的蛋白质疫苗接种策略可能会受益于此类佐剂。临床上安全的脂质体佐剂可以驱动抗体效应子活性，从而相对于明矾增强吞噬功能，并且这种活性可以介导猕猴免受严格粘膜 SHIV 感染的保护。
To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants. A clinically safe liposomal adjuvant can drive antibody effector activity towards increased phagocytic function relative to alum and this activity mediates protection against stringent mucosal SHIV infection in macaques.
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影响因子：
3.7
作者：
Gottardo R;Bailer RT;Korber BT;Gnanakaran S;Phillips J;Shen X;Tomaras GD;Turk E;Imholte G;Eckler L;Wenschuh H;Zerweck J;Greene K;Gao H;Berman PW;Francis D;Sinangil F;Lee C;Nitayaphan S;Rerks-Ngarm S;Kaewkungwal J;Pitisuttithum P;Tartaglia J;Robb ML;Michael NL;Kim JH;Zolla-Pazner S;Haynes BF;Mascola JR;Self S;Gilbert P;Montefiori DC
通讯作者：
Montefiori DC
免疫途径定义了疫苗介导的对SIV的保护的多种机制。
影响因子：
82.9
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
通讯作者：
Alter G
影响因子：
5.4
作者：
Hidajat, Rachmat;Xiao, Peng;Robert-Guroff, Marjorie
通讯作者：
Robert-Guroff, Marjorie
DOI：
10.1073/pnas.89.1.358
发表时间：
1992-01-01
影响因子：
11.1
作者：
FRIES, LF;GORDON, DM;ALVING, CR
通讯作者：
ALVING, CR
DOI：
10.1016/s1473-3099(10)70049-9
发表时间：
2010-05
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Klein SL;Jedlicka A;Pekosz A
通讯作者：
Pekosz A