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

Martinez, David R.; Tu, Joshua J.; Kumar, Amit; Mangold, Jesse F.; Mangan, Riley J.; Goswami, Ria; Giorgi, Elena Edi; Chen, Juilin; Mengual, Michael; Douglas, Ayooluwa O.; Heimsath, Holly; Saunders, Kevin O.; Nicely, Nathan I.; Eudailey, Joshua; Hernandez, Giovanna; Morgan-Asiedu, Papa Kwadwo; Wiehe, Kevin; Haynes, Barton F.; Moody, M. Anthony; LaBranche, Celia; Montefiori, David C.; Gao, Feng; Permar, Sallie R.

doi:10.1128/mbio.00176-20

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

Journal Article · Tue Mar 10 04:00:00 EDT 2020 · mBio (Online)

DOI:https://doi.org/10.1128/mbio.00176-20· OSTI ID:1767003

Martinez, David R. ^[1]; Tu, Joshua J. ^[1]; Kumar, Amit ^[1]; Mangold, Jesse F. ^[1]; Mangan, Riley J. ^[1]; ^[1]; ^[2]; Chen, Juilin ^[1]; Mengual, Michael ^[1]; Douglas, Ayooluwa O. ^[1]; Heimsath, Holly ^[1]; Saunders, Kevin O. ^[1]; Nicely, Nathan I. ^[1]; Eudailey, Joshua ^[1]; Hernandez, Giovanna ^[1]; Morgan-Asiedu, Papa Kwadwo ^[1]; Wiehe, Kevin ^[1]; Haynes, Barton F. ^[1]; Moody, M. Anthony ^[1]; ^[1] more »

Duke Univ., Durham, NC (United States). Medical Center
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1767003

Report Number(s):: LA-UR--21-20585

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 2 Vol. 11; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
HIV
MTCT
antibody
bNAbs
biological science
infant-T/F virus
mother-to-child transmission
neutralization
vertical transmission
virus

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

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