Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants

Author:

Martinez David R.12,Tu Joshua J.2,Kumar Amit2,Mangold Jesse F.2,Mangan Riley J.2,Goswami Ria2ORCID,Giorgi Elena E.3,Chen Juilin12,Mengual Michael4,Douglas Ayooluwa O.2,Heimsath Holly2,Saunders Kevin O.25,Nicely Nathan I.2,Eudailey Joshua2,Hernandez Giovanna2,Morgan-Asiedu Papa Kwadwo2,Wiehe Kevin2,Haynes Barton F.24,Moody M. Anthony26,LaBranche Celia5ORCID,Montefiori David C.25,Gao Feng4,Permar Sallie R.126

Affiliation:

1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA

2. Duke Human Vaccine Institute, Durham, North Carolina, USA

3. Los Alamos National Laboratory, Los Alamos, New Mexico, USA

4. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

5. Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

6. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA

Abstract

Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.

Funder

American Society of Microbiology: Robert D. Watkins Fellowship

HHS | NIH | National Institute of Allergy and Infectious Diseases

Burroughs Wellcome Fund

HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference67 articles.

1. UNAIDS. 2018 Global HIV & AIDS statistics—2018 fact sheet. UNAIDS Geneva Switzerland.

2. Fowler MG, Fiscus SA, Currier JS, Makanani B, Martinson F, Chipato T, Browning R, Shapiro D, Mofenson L. 2015. PROMISE: efficacy and safety of 2 strategies to prevent perinatal HIV transmission. Oral presentation. Conference on Retroviruses and Opportunistic Infections, Seattle, WA.

3. UNAIDS. 2015 Progress report on the global plan: towards the elimination of new HIV infections among children and keeping their mothers alive. UNAIDS Geneva Switzerland.

4. Human placental Fc receptors

5. Mother-to-child transmission of HIV-1 in Congo, central Africa

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