66
views
0
recommends
+1 Recommend
1 collections
    1
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Development of Broadly Neutralizing Antibody Mimitopes for Characterization of CRF01_AE HIV-1 Antibody Responses

      research-article

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mapping humoral immune responses to HIV-1 over the course of natural infection is important in understanding epitope exposure in relation to elicitation of broadly neutralizing antibodies (bNAbs), which is considered imperative for effective vaccine design. When analyzing HIV-specific immune responses, the antibody binding profiles may be a correlate for functional antibody activity. In this study, we utilized phage display technology to identify novel mimitopes that may represent Env epitope structures bound by bNAbs directed at V1V2 and V3 domains, CD4 binding site (CD4bs) and the membrane proximal external region (MPER) of Env. Mimitope sequence motifs were determined for each bNAb epitope. Given the ongoing vaccine development efforts in Thailand, these mimitopes that represent CD4bs and MPER epitopes were used to map immune responses of HIV-1 CRF01_AE-infected individuals with known neutralizing responses from two distinct time periods, 1996-98 and 2012-15. The more contemporary cohort showed an increase in binding breadth with binding observed for all MPER and CD4bs mimitopes, while the older cohort showed only 75% recognition of the CD4bs mimitopes and no MPER mimotope binding. Furthermore, mimitope binding profiles correlated significantly with magnitude ( p=0.0036) and breadth ( p=0.0358) of neutralization of a multi-subtype Tier 1 panel of pseudoviruses. These results highlight the utility of this mimitope mapping approach for detecting human plasma IgG-specificities that target known neutralizing antibody epitopes, and may also provide an indication of the plasticity of antibody binding within HIV-1 Env neutralization determinants.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: found

          Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design.

          HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120.

            A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming virus and either permanently inactivate it or reduce its infectivity, or it could block receptors on susceptible cells near the sites of transmission. We describe here how vaginal administration of the broadly neutralizing human monoclonal antibody b12 can protect macaques from simian-human immunodeficiency virus (SHIV) infection through the vagina. Only 3 of 12 animals receiving 5 mg b12 vaginally in either saline or a gel and then challenged vaginally (up to 2 h later) with SHIV-162P4 became infected. In contrast, infection occurred in 12 of 13 animals given various control agents under similar conditions. Lower amounts of b12 were less effective, suggesting that protection was dose dependent. These observations support the concept that viral entry inhibitors can help prevent the sexual transmission of HIV-1 to humans.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              SAROTUP: Scanner and Reporter of Target-Unrelated Peptides

              As epitope mimics, mimotopes have been widely utilized in the study of epitope prediction and the development of new diagnostics, therapeutics, and vaccines. Screening the random peptide libraries constructed with phage display or any other surface display technologies provides an efficient and convenient approach to acquire mimotopes. However, target-unrelated peptides creep into mimotopes from time to time through binding to contaminants or other components of the screening system. In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. Preliminary tests show that SAROTUP is efficient and capable of improving the accuracy of mimotope-based epitope mapping. It is also helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines.
                Bookmark

                Author and article information

                Contributors
                Journal
                Infectious Diseases and Translational Medicine
                Infect. Dis. Transl. Med.
                Infect. Dis. Transl. Med.
                International Biological and Medical Journals Publishing House Co., Limited (Room E16, 3/f, Yongda Commercial Building, No.97, Bonham Stand (Sheung Wan), HongKong )
                2411-2917
                31 October 2017
                31 October 2017
                : 3
                : 2
                : 25-35 (pp. )
                Affiliations
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
                Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
                Lampang Hospital, Lampang, Thailand
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD
                From U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD
                Author notes
                Correspondence to: Lindsay Wieczorek, Email: lwieczorek@hivresearch.org
                Article
                10.11979/idtm.201702004
                000915fb-04ad-45f9-99e8-66a68bd574ff

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                Page count
                Figures: 7, Tables: 2, References: 45, Pages: 11
                Product
                Categories
                Original Research

                Medicine,Infectious disease & Microbiology
                HIV-1,Neutralizing antibodies,Thailand,Mimitopes,Biopanning,Phage display

                Comments

                Comment on this article