Divide and conquer: broadly neutralizing antibody combinations for improved HIV-1 viral coverage

被引：7

作者：

Wagh, Kshitij ^{[1
,2
,4
,5
]}

Seaman, Michael S. ^{[3
]}

机构：

[1] Los Alamos Natl Lab, Theoret Div, Los Alamos, NM USA

[2] New Mex Consortium, Los Alamos, NM USA

[3] Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA USA

[4] Los Alamos Natl Lab, Theoret Div, Los Alamos, NM 87545 USA

[5] New Mexico Consortium, Los Alamos, NM 87545 USA

来源：

CURRENT OPINION IN HIV AND AIDS | 2023年 / 18卷 / 04期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

Broadly neutralizing antibodies; clinical trials; HIV-1; passive immunization; prevention; therapy;

D O I：

10.1097/COH.0000000000000800

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Purpose of reviewSuccessful HIV-1 prevention and therapy will require broad and potent coverage of within-host and global viral diversity. Broadly neutralizing antibody (bNAb) combination and multispecific therapeutics provide an opportunity to meet this challenge due to the complementary activity of individual antibody components. Here, we review the principles and applications of this concept.Recent findingsThe Antibody Mediated Prevention (AMP) trials have demonstrated the high bar for neutralization potency and breadth that bNAb-mediated prevention modalities will need to achieve to have a meaningful impact on the HIV-1 epidemic. Additional clinical studies have recently shown that an even higher bar may be required for therapeutic inhibition of the diverse within-host quasispecies present in viremic and aviremic people with HIV-1 (PWH). We discuss how the complementarity of bNAbs in terms of neutralization profiles, resistance mutations and coverage of within-host quasispecies may overcome these stringent requirements and lead to effective bNAb combination or multispecific antibody based prophylactic and therapeutic strategies.The design of next-generation bNAb-based combination or multispecific therapeutics for the prevention and/or treatment of HIV-1 infection will need to leverage the complementarity of component bNAbs to maximize the potency and breadth that will be required for clinical success.

引用

页码：164 / 170

页数：7

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