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DOE OSTI · 1767003

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.
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Abstract

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.

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59 BASIC BIOLOGICAL SCIENCESHIVMTCTantibodybNAbsbiological scienceinfant-T/F virusmother-to-child transmissionneutralizationvertical transmissionvirus

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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.. 2020-03-10. Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants. https://doi.org/10.1128/mbio.00176-20

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