Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07-523LS in Newborn Infants Exposed to HIV-1

被引：0

作者：

Cunningham, Coleen K. ^{[1
,2
]}

Mcfarland, Elizabeth J. ^{[3
]}

Muresan, Petronella ^{[4
]}

Capparelli, Edmund, V ^{[5
,6
,7
]}

Perlowski, Charlotte ^{[8
]}

Johnston, Benjamin ^{[9
]}

Bone, Frederic ^{[9
]}

Purdue, Lynette ^{[10
]}

Yin, Dwight E. ^{[11
]}

Moye, Jack ^{[12
]}

Spiegel, Hans M. L. ^{[13
]}

Majji, Sai ^{[12
]}

Theron, Gerhard B. ^{[14
]}

Mujuru, Hilda A. ^{[15
]}

Purswani, Murli ^{[16
]}

Alvarez, Grace ^{[17
]}

Deville, Jaime G. ^{[18
]}

Chambers, Carrie ^{[3
]}

Brown, Emily ^{[8
]}

Harding, Paul A. ^{[3
]}

Tobin, Nicole H. ^{[18
]}

Low, Kwang ^{[19
]}

Gama, Lucio ^{[19
]}

机构：

[1] Univ Calif Irvine, Dept Pediat, 3800 West Chapman Ave,Suite 200, Orange, CA 92868 USA

[2] Childrens Hosp Orange Cty, Div Infect Dis, Orange, CA 92868 USA

[3] Univ Colorado, Dept Pediat, Anschutz Med Campus, Aurora, CO 80045 USA

[4] Boston Univ, Ctr Informat & Syst Engn, Brookline, MA 02446 USA

[5] UC San Diego Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[6] UC San Diego Sch Med, Dept Pharm, La Jolla, CA 92093 USA

[7] Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[8] FHI 360, Durham, NC 27701 USA

[9] Frontier Sci Technol & Res Fdn, Amherst, NY 14226 USA

[10] NIAID, Bethesda, MD USA

[11] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA

[12] Branch Eunice Kennedy Shriver Natl Inst Child Hlth, NIH, Bethesda, MD USA

[13] NIAID, Kelly Govt Solut, NIH, Dept HHS, Rockville, MD USA

[14] Stellenbosch Univ, Fac Med & Hlth Sci, Dept Obstet & Gynaecol, Cape Town, South Africa

[15] Univ Zimbabwe, Coll Hlth Sci, Clin Trials Res Ctr UZCHS CTRC, Harare, Zimbabwe

[16] BronxCare Hlth Syst, Dept Pediat, Div Pediat Infect Dis, Bronx, NY USA

[17] Univ Miami, Miller Sch Med, Miami, FL USA

[18] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA

[19] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY | 2025年 / 14卷 / 02期

关键词：

broadly neutralizing antibodies; VRC07-523LS; vertical HIV-1 transmission; pharmacokinetics; HIV-1; prevention; IDENTIFICATION; TRANSMISSION; DELIVERY; POTENCY; BURDEN; TRIALS; WOMEN;

D O I：

10.1093/jpids/piaf002

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by the use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07-523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07-523LS.Methods VRC07-523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (cohort 1; N = 11, enrolled in USA) and breastfed (cohort 2; N = 11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1. Breastfed infants (cohort 2) received a second 100-mg dose at 12 weeks if still receiving breastmilk. All infants received antiretroviral prophylaxis in addition to VRC07-523LS. VRC07-523LS levels were compared to VRC01 levels, as determined previously in this study.Results Local reactions (all grade <= 2) occurred after dose 1 in 18% of infants in cohort 1 and after doses 1 and 2 in 100% of infants in cohort 2. The VRC07-523LS dose at birth (mean 26 mg/kg) achieved a mean +/- SD plasma level of 222.3 +/- 71.6 mcg/mL by 24 hours and 18.4 +/- 7.2 mcg/mL at week 12, prior to dose 2. The pre-established target of >= 10 mcg/mL at week 12 was met in 94% of infants. The terminal half-life of VRC07-523LS was observed to be 39.2 +/- 5.0 days. At week 4 and week 8, bNAb levels were significantly higher (P <= .002) after one dose of VRC07-523LS, compared to one dose of VRC01 (20 mg/kg). No infant included in the study acquired HIV-1.Conclusions VRC07-523LS was well tolerated with pharmacokinetics that support further studies of potent long-acting bNAbs together with antiretrovirals to prevent HIV-1 acquisition in infants. Broadly neutralizing monoclonal antibodies (bNAb) have been shown to reduce HIV- transmission from sensitive virus in adults. The present study is the first to demonstrate the safety and pharmacokinetics of the bNAb VRC07-523LS in neonates exposed to HIV-1.

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页数：8

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