Diversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical Transmission
| Autor: | Theodore A Gobillot, Meghan Garrett, Ruth Nduati, Frederick A. Matsen, Cassandra A. Simonich, Mackenzie M. Shipley, Vladimir Vigdorovich, Laura E Doepker, D. Noah Sather, Duncan Ralph, Julie Overbaugh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
Immunology HIV Infections V3 loop HIV Antibodies Monoclonal antibody Microbiology Virus 03 medical and health sciences Epitopes 0302 clinical medicine Immune system Antibody Specificity Pregnancy Virology medicine Humans HIV vaccine Pregnancy Complications Infectious 030304 developmental biology Antibody-dependent cell-mediated cytotoxicity AIDS Vaccines 0303 health sciences biology Transmission (medicine) env Gene Products Human Immunodeficiency Virus Antibodies Monoclonal Infant Antibodies Neutralizing Infectious Disease Transmission Vertical Insect Science biology.protein HIV-1 Pathogenesis and Immunity Female Antibody 030217 neurology & neurosurgery |
| Zdroj: | J Virol |
| Popis: | Infants of HIV-positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV-specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families and employed a variety of VH genes. Many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous or autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant, even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire; all were less than 0.25% of total IgG sequences. Our findings illustrate an example of the diversity of HIV-1 nAbs within one mother, cumulatively resulting in a collection of antibody specificities that can contribute to the transmission bottleneck. IMPORTANCE Mother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30 to 40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV is a central goal of HIV vaccine design, understanding the nature of maternal antibodies may provide insights into immune mechanisms of protection. In this study, we isolated and characterized HIV-specific antibodies from the mother of an infant whose transmitted virus has been well studied. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|