Dataset Information

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.

ABSTRACT: To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.To investigate whether variants transmitted during MTCT are generally resistant to HIV-1-specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9 and PGT145.Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus nontransmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared with heterosexually transmitted variants, vertically transmitted variants were significantly more sensitive to neutralization by PGT128 and PGT121 (P=0.03 in both cases), but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45-46 (P=0.04), VRC01 (P=0.002) and PGT145 (P=0.03) compared with the nonsubtype A and less sensitive to PGT121 than subtype Cs (P=0.0001).A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes.

SUBMITTER: Mabuka J

PROVIDER: S-EPMC4080909 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.

Mabuka Jennifer J Goo Leslie L Omenda Maxwel M MM Nduati Ruth R Overbaugh Julie J

AIDS (London, England) 20130601 10

<h4>Rationale</h4>To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.<h4>Method</h4>To investigate whether varian ...[more]

PMID: 23856624

Similar Datasets

Project description:Broadly neutralizing antibodies (bNAbs) for HIV-1 prevention or cure strategies must inhibit transmitted/founder and reservoir viruses. Establishing sensitivity of circulating viruses to bNAbs and genetic patterns affecting neutralization variability may guide rational bNAbs selection for clinical development. We analyzed 326 single env genomes from nine individuals followed longitudinally following acute HIV-1 infection, with samples collected at ~1 week after the first detection of plasma viremia; 300 to 1,709 days postinfection but prior to initiating antiretroviral therapy (ART) (median = 724 days); and ~1 year post ART initiation. Sequences were assessed for phylogenetic relatedness, potential N- and O-linked glycosylation, and variable loop lengths (V1 to V5). A total of 43 env amplicons (median = 3 per patient per time point) were cloned into an expression vector and the TZM-bl assay was used to assess the neutralization profiles of 15 bNAbs targeting the CD4 binding site, V1/V2 region, V3 supersite, MPER, gp120/gp41 interface, and fusion peptide. At 1 μg/mL, the neutralization breadths were as follows: VRC07-LS and N6.LS (100%), VRC01 (86%), PGT151 (81%), 10-1074 and PGT121 (80%), and less than 70% for 10E8, 3BNC117, CAP256.VRC26, 4E10, PGDM1400, and N123-VRC34.01. Features associated with low sensitivity to V1/V2 and V3 bNAbs were higher potential glycosylation sites and/or relatively longer V1 and V4 domains, including known "signature" mutations. The study shows significant variability in the breadth and potency of bNAbs against circulating HIV-1 subtype C envelopes. VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants, and major determinants of sensitivity to most bNAbs were within the V1/V4 domains. IMPORTANCE Broadly neutralizing antibodies (bNAbs) have potential clinical utility in HIV-1 prevention and cure strategies. However, bNAbs target diverse epitopes on the HIV-1 envelope and the virus may evolve to evade immune responses. It is therefore important to identify antibodies with broad activity in high prevalence settings, as well as the genetic patterns that may lead to neutralization escape. We investigated 15 bNAbs with diverse biophysical properties that target six epitopes of the HIV-1 Env glycoprotein for their ability to inhibit viruses that initiated infection, viruses circulating in plasma at chronic infection before antiretroviral treatment (ART), or viruses that were archived in the reservoir during ART in subtype C infected individuals in South Africa, a high burden country. We identify the antibodies most likely to be effective for clinical use in this setting and describe mutational patterns associated with neutralization escape from these antibodies.

Dataset Information

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.

Publications

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets