Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

被引：71

作者：

Gilbert, Peter B. ^{[1
,2
]}

Huang, Yunda ^{[1
,3
]}

deCamp, Allan C. ^{[1
]}

Karuna, Shelly ^{[1
]}

Zhang, Yuanyuan ^{[1
]}

Magaret, Craig A. ^{[1
]}

Giorgi, Elena E. ^{[4
,26
]}

Korber, Bette ^{[4
]}

Edlefsen, Paul T. ^{[1
]}

Rossenkhan, Raabya ^{[1
]}

Juraska, Michal ^{[1
]}

Rudnicki, Erika ^{[1
]}

Kochar, Nidhi ^{[1
]}

Huang, Ying ^{[1
]}

Carpp, Lindsay N. ^{[1
]}

Barouch, Dan H. ^{[5
,6
]}

Mkhize, Nonhlanhla N. ^{[7
,8
]}

Hermanus, Tandile ^{[7
,8
]}

Kgagudi, Prudence ^{[7
,8
]}

Bekker, Valerie ^{[7
,8
,10
,11
,12
]}

Kaldine, Haajira ^{[7
,8
]}

Mapengo, Rutendo E. ^{[7
,8
]}

Eaton, Amanda ^{[9
]}

Domin, Elize ^{[8
,9
]}

West, Carley ^{[9
]}

Feng, Wenhong ^{[9
]}

Tang, Haili ^{[9
]}

Seaton, Kelly E. ^{[10
,11
,12
]}

Heptinstall, Jack ^{[10
,11
,12
]}

Brackett, Caroline ^{[10
,11
,12
]}

Chiong, Kelvin ^{[10
,11
,12
]}

Tomaras, Georgia D. ^{[10
,11
,12
]}

Andrew, Philip ^{[13
]}

Mayer, Bryan T. ^{[1
]}

Reeves, Daniel B. ^{[1
]}

Sobieszczyk, Magdalena E. ^{[14
]}

Garrett, Nigel ^{[15
,16
]}

Sanchez, Jorge ^{[17
]}

Gay, Cynthia ^{[18
]}

Makhema, Joseph ^{[19
,20
]}

Williamson, Carolyn ^{[21
]}

Mullins, James I. ^{[3
,22
,23
]}

Hural, John ^{[1
]}

Cohen, Myron S. ^{[24
]}

Corey, Lawrence ^{[23
,25
]}

Montefiori, David C. ^{[9
]}

Morris, Lynn ^{[7
,8
,15
]}

机构：

[1] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[2] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[3] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

[4] Los Alamos Natl Lab, Los Alamos, NM USA

[5] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[6] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA

[7] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa

[8] Univ Witwatersrand, Fac Hlth Sci, Antibody Immun Res Unit, Johannesburg, South Africa

[9] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[10] Duke Univ, Duke Ctr Human Syst Immunol, Dept Surg, Durham, NC USA

[11] Duke Univ, Duke Ctr Human Syst Immunol, Dept Immunol, Durham, NC USA

[12] Duke Univ, Duke Ctr Human Syst Immunol, Dept Mol Genet & Micobiol, Durham, NC USA

[13] Family Hlth Int, Durham, NC USA

[14] Columbia Univ, Irving Med Ctr, Dept Med, Div Infect Dis, New York, NY USA

[15] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa, Durban, South Africa

[16] Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth Med, Durban, South Africa

[17] Univ Nacl Mayor San Marcos, Ctr Invest Tecnol Biomed & Medioambientales, Lima, Peru

[18] Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27515 USA

[19] Botswana Harvard AIDS Initiat Partnership HIV Res, Gaborone, Botswana

[20] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA

[21] Univ Cape Town, Fac Hlth Sci, Div Med Virol, Cape Town, South Africa

[22] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA

[23] Univ Washington, Dept Med, Seattle, WA USA

[24] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC 27515 USA

[25] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

[26] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA

来源：

NATURE MEDICINE | 2022年 / 28卷 / 09期

基金：

英国医学研究理事会; 比尔及梅琳达.盖茨基金会;

关键词：

PROTECTION;

D O I：

10.1038/s41591-022-01953-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT80 biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition. The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT80 of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. Based on this result, we suggest that the goal of sustained PT80 <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT80 biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.

引用

页码：1924 / +

页数：27

共 45 条

[1] Duration of humoral immunity to common viral and vaccine antigens [J].

Amanna, Ian J. ;

Carlson, Nichole E. ;

Slifka, Mark K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (19) :1903-1915

[2]

[Anonymous], 2022, Dual Compensation Waiver Requests for COVID-19 Emergency

[3] Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge [J].

Astronomo, Rena D. ;

Lemos, Maria P. ;

Narpala, Sandeep R. ;

Czartoski, Julie ;

Fleming, Lamar Ballweber ;

Seaton, Kelly E. ;

Prabhakaran, Madhu ;

Huang, Yunda ;

Lu, Yiwen ;

Westerberg, Katharine ;

Zhang, Lily ;

Gross, Mary K. ;

Hural, John ;

Tieu, Hong-Van ;

Baden, Lindsey R. ;

Hammer, Scott ;

Frank, Ian ;

Ochsenbauer, Christina ;

Grunenberg, Nicole ;

Ledgerwood, Julie E. ;

Mayer, Kenneth ;

Tomaras, Georgia ;

McDermott, Adrian B. ;

McElrath, M. Juliana .

JOURNAL OF CLINICAL INVESTIGATION, 2021, 131 (16)

[4] The complex challenges of HIV vaccine development require renewed and expanded global commitment [J].

Bekker, Linda-Gail ;

Tatoud, Roger ;

Dabis, Francois ;

Feinberg, Mark ;

Kaleebu, Pontiano ;

Marovich, Mary ;

Ndung'u, Thumbi ;

Russell, Nina ;

Johnson, Jeremiah ;

Luba, Maureen ;

Fauci, Anthony S. ;

Morris, Lynn ;

Pantaleo, Giuseppe ;

Buchbinder, Susan ;

Gray, Glenda ;

Vekemans, Johan ;

Kim, Jerome H. ;

Levy, Yves ;

Corey, Lawrence ;

Shattock, Robin ;

Makanga, Michael ;

Williamson, Carolyn ;

Dieffenbach, Carl ;

Goodenow, Maureen M. ;

Shao, Yiming ;

Staprans, Silvija ;

Warren, Mitchell ;

Johnston, Margaret I. .

LANCET, 2020, 395 (10221) :384-388

[5] Amping up HIV antibodies [J].

Burton, Dennis R. .

SCIENCE, 2021, 372 (6549) :1397-1398

[6]

Carroll RJ., 2006, Measurement Error in Nonlinear Models: a Modern Perspective

[7] Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study [J].

Cohen, Yehuda Z. ;

Butler, Allison L. ;

Millard, Katrina ;

Witmer-Pack, Maggi ;

Levin, Rebeka ;

Unson-O'Brien, Cecilia ;

Patel, Roshni ;

Shimeliovich, Irina ;

Lorenzi, Julio C. C. ;

Horowitz, Jill ;

Walsh, Stephen R. ;

Lin, Shu ;

Weiner, Joshua A. ;

Tse, Anna ;

Sato, Alicia ;

Bennett, Chelsey ;

Mayer, Bryan ;

Seaton, Kelly E. ;

Yates, Nicole L. ;

Baden, Lindsey R. ;

deCamp, Allan C. ;

Ackerman, Margaret E. ;

Seaman, Michael S. ;

Tomaras, Georgia D. ;

Nussenzweig, Michel C. ;

Caskey, Marina .

PLOS ONE, 2019, 14 (08)

[8] Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition [J].

Corey, L. ;

Gilbert, P. B. ;

Juraska, M. ;

Montefiori, D. C. ;

Morris, L. ;

Karuna, S. T. ;

Edupuganti, S. ;

Mgodi, N. M. ;

deCamp, A. C. ;

Rudnicki, E. ;

Huang, Y. ;

Gonzales, P. ;

Cabello, R. ;

Orrell, C. ;

Lama, J. R. ;

Laher, F. ;

Lazarus, E. M. ;

Sanchez, J. ;

Frank, I. ;

Hinojosa, J. ;

Sobieszczyk, M. E. ;

Marshall, K. E. ;

Mukwekwerere, P. G. ;

Makhema, J. ;

Baden, L. R. ;

Mullins, J. I. ;

Williamson, C. ;

Hural, J. ;

McElrath, M. J. ;

Bentley, C. ;

Takuva, S. ;

Lorenzo, M. M. Gomez ;

Burns, D. N. ;

Espy, N. ;

Randhawa, A. K. ;

Kochar, N. ;

Piwowar-Manning, E. ;

Donnell, D. J. ;

Sista, N. ;

Andrew, P. ;

Kublin, J. G. ;

Gray, G. ;

Ledgerwood, J. E. ;

Mascola, J. R. ;

Cohen, M. S. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (11) :1003-1014

[9] Evidence for antibody as a protective correlate for COVID-19 vaccines [J].

Earle, Kristen A. ;

Ambrosino, Donna M. ;

Fiore-Gartland, Andrew ;

Goldblatt, David ;

Gilbert, Peter B. ;

Siber, George R. ;

Dull, Peter ;

Plotkin, Stanley A. .

VACCINE, 2021, 39 (32) :4423-4428

[10]

Fong Youyi, 2022, medRxiv, DOI 10.1101/2022.04.06.22272763

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