Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1

Coleen K Cunningham; Elizabeth J McFarland; Petronella Muresan; Edmund V Capparelli; Charlotte Perlowski; Benjamin Johnston; Frederic Bone; Lynette Purdue; Dwight E Yin; Jack Moye; Hans M L Spiegel; Sai Majji; Gerhard B Theron; Hilda A Mujuru; Murli Purswani; Grace Alvarez; Jaime G Deville; Carrie Chambers; Emily Brown; Paul A Harding; Nicole H Tobin; Kwang Low; Lucio Gama; IMPAACT P1112 team

doi:10.1093/jpids/piaf002

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1

J Pediatric Infect Dis Soc. 2025 Jan 16:piaf002. doi: 10.1093/jpids/piaf002. Online ahead of print.

Authors

Coleen K Cunningham^{1

2}, Elizabeth J McFarland³, Petronella Muresan⁴, Edmund V Capparelli⁵, Charlotte Perlowski⁶, Benjamin Johnston⁷, Frederic Bone⁷, Lynette Purdue⁸, Dwight E Yin⁹, Jack Moye¹⁰, Hans M L Spiegel¹¹, Sai Majji¹⁰, Gerhard B Theron¹², Hilda A Mujuru¹³, Murli Purswani¹⁴, Grace Alvarez¹⁵, Jaime G Deville¹⁶, Carrie Chambers³, Emily Brown⁶, Paul A Harding³, Nicole H Tobin¹⁶, Kwang Low¹⁷, Lucio Gama¹⁷; IMPAACT P1112 team

Affiliations

¹ Department of Pediatrics, University of California, Irvine, Orange, CA, USA.
² Division of Infectious Diseases, Children's Hospital of Orange County, Orange, CA, USA.
³ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Statistical and Data Management Center/ Frontier Science and Technology Research Foundation, Brookline, MA, USA.
⁵ Department of Pediatrics and Pharmacy, UC San Diego Schools of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA.
⁶ FHI 360, Durham, NC, USA.
⁷ Frontier Science Foundation, Amherst, NY, USA.
⁸ National Institute of Allergy and Infectious Diseases, Division of AIDS (Contractor), Bethesda, MD, USA.
⁹ Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Maternal and Pediatric Infectious Disease Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Bethesda, MD, USA.
¹¹ Kelly Government Solutions, Contractor to NIAID/NIH/HHS, Rockville, MD, USA.
¹² Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹³ University of Zimbabwe College of Health Sciences - Clinical Trials Research Centre (UZCHS-CTRC), Zimbabwe.
¹⁴ Division of Pediatric Infectious Disease, Department of Pediatrics, BronxCare Health Systems (affiliated with Icahn School of Medicine at Mount Sinai), Bronx, NY, USA.
¹⁵ University of Miami Miller School of Medicine, Miami, FL, USA.
¹⁶ Department of Pediatrics, University of California, Los Angeles,CA, USA.
¹⁷ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH Bethesda, MD, USA.

PMID: 39821046
DOI: 10.1093/jpids/piaf002

Abstract

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 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 VRC07523LS. VRC07523LS 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 VRC07523LS 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 VRC07523LS was observed to be 39.2±5.0 days. At Week 4 and Week 8, bNAb levels were significantly higher (p≤0.002) after one dose of VRC07523LS, compared to one dose of VRC01 (20 mg/kg). No infant included in the study acquired HIV-1.

Conclusions: VRC07523LS was well tolerated with pharmacokinetics that support further studies of potent long-acting bNAbs together with antiretrovirals to prevent HIV-1 acquisition in infants.

Keywords: Broadly neutralizing antibodies; HIV-1 prevention; VRC07523LS; pharmacokinetics; vertical HIV-1 transmission.

Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US.