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. 2025 Feb 6;14(2):piaf002.
doi: 10.1093/jpids/piaf002.

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

Coleen K Cunningham  1   2 , Elizabeth J McFarland  3 , Petronella Muresan  4 , Edmund V Capparelli  5 , Charlotte Perlowski  6 , Benjamin Johnston  7 , Frederic Bone  7 , Lynette Purdue  8 , Dwight E Yin  9 , Jack Moye  10 , Hans M L Spiegel  11 , Sai Majji  10 , Gerhard B Theron  12 , Hilda A Mujuru  13 , Murli Purswani  14 , Grace Alvarez  15 , Jaime G Deville  16 , Carrie Chambers  3 , Emily Brown  6 , Paul A Harding  3 , Nicole H Tobin  16 , Kwang Low  17 , Lucio Gama  17
Affiliations

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

Coleen K Cunningham et al. J Pediatric Infect Dis Soc. .

Abstract

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.

Keywords: HIV-1 prevention; VRC07–523LS; broadly neutralizing antibodies; pharmacokinetics; vertical HIV-1 transmission.

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Conflict of interest statement

CKC was previously a paid consultant to IAVI. DEY was previously an unpaid technical advisor for the non-profits Cover the Globe and Maipelo Trust. The data in this manuscript were previously presented, in part, at the Conference on Retroviruses and Opportunistic Infections on February 12-16, 2022, Denver, CO, Oral Abstract 0732.

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