NFPws: a web server for delineating broadly neutralizing antibody specificities from serum HIV-1 neutralization data

MOTIVATION A better understanding of antibody responses to HIV-1 infection in humans can provide novel insights for the development of an effective HIV-1 vaccine. Neutralization fingerprinting (NFP) is an efficient and accurate algorithm for delineating the epitope specificities found in polyclonal antibody responses to HIV-1 infection. Here, we report the development of NFPws, a web server implementation of the NFP algorithm. The server takes as input serum neutralization data for a set of diverse viral strains, and uses a mathematical model to identify similarities between the serum neutralization pattern and the patterns for known broadly neutralizing monoclonal antibodies (bNAbs), in order to predict the prevalence of bNAb epitope specificities in the given serum. In addition, NFPws also computes and displays a number of estimates related to prediction confidence, as well as the likelihood of presence of novel, previously uncharacterized, antibody specificities in a given serum. NFPws also implements a JSmol viewer for molecular structure visualization of the prediction results. Overall, the NFPws server will be an important tool for the identification and analysis of epitope specificities of bNAb responses against HIV-1. AVAILABILITY AND IMPLEMENTATION NFPws is freely available to access at (http://iglab.accre.vanderbilt.edu/NFPws). The webserver is developed using html, CSS, javascript and perl CGI scripts. The NFP algorithm is implemented with scripts written in octave, linux shell and perl. JSmol is implemented to visualize the prediction results on a representative 3D structure of an HIV-1 antigen.

[1]  Tongqing Zhou,et al.  Structure and immune recognition of trimeric prefusion HIV-1 Env , 2014, Nature.

[2]  I. Wilson,et al.  Insights into the trimeric HIV-1 envelope glycoprotein structure. , 2015, Trends in biochemical sciences.

[3]  Young Do Kwon,et al.  Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G , 2016, Cell.

[4]  Tongqing Zhou,et al.  Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization , 2013, Science.

[5]  Ben Murrell,et al.  Identification of broadly neutralizing antibody epitopes in the HIV-1 envelope glycoprotein using evolutionary models , 2013, Virology Journal.

[6]  Daniel W. Kulp,et al.  Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice , 2015, Cell.

[7]  Dennis R. Burton,et al.  A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals , 2010, PLoS pathogens.

[8]  Lynn Morris,et al.  Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting , 2017, PLoS pathogens.

[9]  T. Kepler,et al.  Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design , 2012, Journal of Virology.

[10]  David Nemazee,et al.  Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen , 2015, Science.

[11]  I. Georgiev,et al.  Elicitation of HIV-1-neutralizing antibodies against the CD4-binding site. , 2013, Current opinion in HIV and AIDS.

[12]  Gwo-Yu Chuang,et al.  Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface , 2014, Nature.

[13]  L. Rychlewski,et al.  Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines , 2013, Virology Journal.

[14]  Florian Klein,et al.  Computational analysis of anti–HIV-1 antibody neutralization panel data to identify potential functional epitope residues , 2013, Proceedings of the National Academy of Sciences.

[15]  J. Sodroski,et al.  The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. , 1998, Science.