Logo
  • Careers
  • Contact Us
  • Donate
  • Subscribe
Search
  • Home
  • About
    • About
    • Board of Directors
    • Senior Leadership
    • Financial Statements
    • Global Funding & Support
    • Our History: 1995-2021
  • Our Work
    • Our Work
    • Discovery & Research
      • HIV Vaccine Translational Research Laboratory
      • Human Immunology Laboratory
      • IAVI Neutralizing Antibody Center
      • Vaccine Design and Development Laboratory
      • Clinical Research Centers
      • Clinical Research Standards
      • HIV Epidemiology Studies
      • IAVI in Africa
    • Translation & Product Development
    • Global Access to Scientific Innovations
    • ADVANCE
      • IAVI DataSpace
    • Advocacy & Community Engagement
      • CASPR
      • Tuberculosis R&D Advocacy
      • World Bank/Japan-supported
        Partnerships | 日本政府・世銀が支援するパートナーシップ
  • Our Science
    • Our Science
    • Pipeline
    • HIV Vaccines
    • bnAbs for HIV Prevention
    • Tuberculosis Vaccines
    • Emerging Infectious Diseases Vaccines
  • News & Resources
    • Latest NewsLatest News
    • Scientific Publications Scientific Publications
    • Press Releases
    • Features
    • IAVI Report
    • IAVI in the News
    • Fact Sheets & Publications
    • VOICES Newsletter
    • Multimedia
    • Media Contacts
    • Subscribe
  • Careers
  • Contact Us
  • Donate
  • Subscribe

Search

  • Home
  • About
    • About
    • Board of Directors
    • Senior Leadership
    • Financial Statements
    • Global Funding & Support
    • Our History: 1995-2021
  • Our Work
    • Our Work
    • Discovery & Research
    • Translation & Product Development
    • Global Access to Scientific Innovations
    • ADVANCE
    • Advocacy & Community Engagement
  • Our Science
    • Our Science
    • Pipeline
    • HIV Vaccines
    • bnAbs for HIV Prevention
    • Tuberculosis Vaccines
    • Emerging Infectious Diseases Vaccines
  • News & Resources
    • Latest NewsLatest News
    • Scientific Publications Scientific Publications
    • Press Releases
    • Features
    • IAVI Report
    • IAVI in the News
    • Fact Sheets & Publications
    • VOICES Newsletter
    • Multimedia
    • Media Contacts
    • Subscribe
  • Latest NewsLatest News
  • Scientific Publications Scientific Publications
  • Press Releases
  • Features
  • IAVI Report
  • IAVI in the News
  • Fact Sheets & Publications
  • VOICES Newsletter
  • Multimedia
  • Media Contacts
  • Subscribe

Scientific Publications

Filter By:

 

 
Filters

Xu L, Pegu A, Rao E, Doria-Rose N, Beninga J, McKee K, Lord DM, Wei RR, Deng G, Louder M, Schmidt SD, Mankoff Z, Wu L, Asokan M, Beil C, Lange C, Leuschner WD, Kruip J, Sendak R, Kwon YD, Zhou T, Chen X, Bailer RT, Wang K, Choe M, Tartaglia LJ, Barouch DH, O'Dell S, Todd JP, Burton DR, Roederer M, Connors M, Koup RA, Kwong PD, Yang ZY, Mascola JR, Nabel GJ

Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 2017;358(6359):85-90 doi: 10.1126/science.aan8630

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.

Topics: HIV Challenge Studies, HIV Neutralizing Antibodies

van Gils MJ, van den Kerkhof TL, Ozorowski G, Cottrell CA, Sok D, Pauthner M, Pallesen J, de Val N, Yasmeen A, de Taeye SW, Schorcht A, Gumbs S, Johanna I, Saye-Francisco K, Liang CH, Landais E, Nie X, Pritchard LK, Crispin M, Kelsoe G, Wilson IA, Schuitemaker H, Klasse PJ, Moore JP, Burton DR, Ward AB, Sanders RWAn HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nat Microbiol 2016;2:16199 doi: 10.1038/nmicrobiol.2016.199

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

The induction by vaccination of broadly neutralizing antibodies (bNAbs) capable of neutralizing various HIV-1 viral strains is challenging, but understanding how a subset of HIV-infected individuals develops bNAbs may guide immunization strategies. Here, we describe the isolation and characterization of the bNAb ACS202 from an elite neutralizer that recognizes a new, trimer-specific and cleavage-dependent epitope at the gp120-gp41 interface of the envelope glycoprotein (Env), involving the glycan N88 and the gp41 fusion peptide. In addition, an Env trimer, AMC011 SOSIP.v4.2, based on early virus isolates from the same elite neutralizer, was constructed, and its structure by cryo-electron microscopy at 6.2 Å resolution reveals a closed, pre-fusion conformation similar to that of the BG505 SOSIP.664 trimer. The availability of a native-like Env trimer and a bNAb from the same elite neutralizer provides the opportunity to design vaccination strategies aimed at generating similar bNAbs against a key functional site on HIV-1.

Kratochvil S, McKay PF, Kopycinski JT, Bishop C, Hayes PJ, Muir L, Pinder CL, Cizmeci D, King D, Aldon Y, Wines BD, Hogarth PM, Chung AW, Kent SJ, Held K, Geldmacher C, Dally L, Santos NS, Cole T, Gilmour J, Fidler S, Shattock RJ

A Phase 1 Human Immunodeficiency Virus Vaccine Trial for Cross-Profiling the Kinetics of Serum and Mucosal Antibody Responses to CN54gp140 Modulated by Two Homologous Prime-Boost Vaccine Regimens. Front Immunol 2017;8:595 doi: 10.3389/fimmu.2017.00595

Abstract & Topics (Click to display abstract, topics and IAVI Projects)    

A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months. The two homologous prime-boost regimens were well tolerated and induced CN54gp140-specific responses that were observed in both the systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with FcγR engagement, and both vaccine regimens were associated with strikingly similar patterns in antibody titer and FcγR-binding profiles. In both groups, identical changes in the antigen (Ag)-specific IgG-subclass fingerprint, leading to a decrease in IgG1 and an increase in IgG4 levels, were modulated by booster injections. Here, the dissection of immune profiles further supports the notion that prime-boost strategies are essential for the induction of diverse Ag-specific HIV-1 responses. The results reported here clearly demonstrate that identical responses were effectively and safely induced by both vaccine regimens, indicating that an accelerated 6-month regimen could be employed for the rapid induction of immune responses against CN54gp140 with no apparent impact on the overall quality of the induced immune response. (This study has been registered at https://ClinicalTrials.gov under registration no. NCT01966900.).

Topics: IAVI Clinical Trial

Keywords: X001

Zhou T, Doria-Rose NA, Cheng C, Stewart-Jones GBE, Chuang GY, Chambers M, Druz A, Geng H, McKee K, Kwon YD, O'Dell S, Sastry M, Schmidt SD, Xu K, Chen L, Chen RE, Louder MK, Pancera M, Wanninger TG, Zhang B, Zheng A, Farney SK, Foulds KE, Georgiev IS, Joyce MG, Lemmin T, Narpala S, Rawi R, Soto C, Todd JP, Shen CH, Tsybovsky Y, Yang Y, Zhao P, Haynes BF, Stamatatos L, Tiemeyer M, Wells L, Scorpio DG, Shapiro L, McDermott AB, Mascola JR, Kwong PDQuantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep 2017;19(4):719-732 doi: S2211-1247(17)30488-6

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.

Safrit JT, Tomaras GD, Hanke T, deCamp AC, Voronin YThe Landscape of Targeted Immune Responses in the HIV-1 Vaccine Field. AIDS Res. Hum. Retroviruses ;32(10-11):944-946

Abstract & Topics (Click to display abstract, topics and IAVI Projects)    

Kassanjee R, Pilcher CD, Busch MP, Murphy G, Facente SN, Keating SM, Mckinney E, Marson K, Price MA, Martin JN, Little SJ, Hecht FM, Kallas EG, Welte AViral load criteria and threshold optimization to improve HIV incidence assay characteristics. AIDS 2016;30(15):2361-71 doi: 10.1097/QAD.0000000000001209

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

Assays for classifying HIV infections as 'recent' or 'nonrecent' for incidence surveillance fail to simultaneously achieve large mean durations of 'recent' infection (MDRIs) and low 'false-recent' rates (FRRs), particularly in virally suppressed persons. The potential for optimizing recent infection testing algorithms (RITAs), by introducing viral load criteria and tuning thresholds used to dichotomize quantitative measures, is explored.

Sok D, Le KM, Vadnais M, Saye-Francisco KL, Jardine JG, Torres JL, Berndsen ZT, Kong L, Stanfield R, Ruiz J, Ramos A, Liang CH, Chen PL, Criscitiello MF, Mwangi W, Wilson IA, Ward AB, Smider VV, Burton DR

Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows. Nature 2017;548(7665):108-111 doi: 10.1038/nature23301

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens that antigenically mimic the HIV envelope glycoprotein (Env), such as the soluble cleaved trimer BG505 SOSIP, have improved the elicitation of potent isolate-specific antibody responses in rabbits and macaques, but so far failed to induce broadly neutralizing antibodies. One possible reason for this failure is that the relevant antibody repertoires are poorly suited to target the conserved epitope regions on Env, which are somewhat occluded relative to the exposed variable epitopes. Here, to test this hypothesis, we immunized four cows with BG505 SOSIP. The antibody repertoire of cows contains long third heavy chain complementary determining regions (HCDR3) with an ultralong subset that can reach more than 70 amino acids in length. Remarkably, BG505 SOSIP immunization resulted in rapid elicitation of broad and potent serum antibody responses in all four cows. Longitudinal serum analysis for one cow showed the development of neutralization breadth (20%, n = 117 cross-clade isolates) in 42 days and 96% breadth (n = 117) at 381 days. A monoclonal antibody isolated from this cow harboured an ultralong HCDR3 of 60 amino acids and neutralized 72% of cross-clade isolates (n = 117) with a potent median IC of 0.028 μg ml. Breadth was elicited with a single trimer immunogen and did not require additional envelope diversity. Immunization of cows may provide an avenue to rapidly generate antibody prophylactics and therapeutics to address disease agents that have evolved to avoid human antibody responses.

Topics: HIV Neutralizing Antibodies

Moldt B, Le KM, Carnathan DG, Whitney JB, Schultz N, Lewis MG, Borducchi EN, Smith KM, Mackel JJ, Sweat SL, Hodges AP, Godzik A, Parren PW, Silvestri G, Barouch DH, Burton DRNeutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques. AIDS 2016;30(10):1543-51 doi: 10.1097/QAD.0000000000001102

Abstract & Topics (Click to display abstract, topics and IAVI Projects)     FREE PMC ARTICLE

Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126.

Obuku AE, Asiki G, Abaasa A, Ssonko I, Harari A, van Dam GJ, Corstjens PL, Joloba M, Ding S, Mpendo J, Nielsen L, Kamali A, Elliott AM, Pantaleo G, Kaleebu P, Pala PEffect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk. AIDS Res. Hum. Retroviruses 2016;32(7):668-75 doi: 10.1089/AID.2015.0274

Abstract & Topics (Click to display abstract, topics and IAVI Projects)    

In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and β-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals.

Hayes PJ, Cox JH, Coleman AR, Fernandez N, Bergin PJ, Kopycinski JT, Nitayaphan S, Pitisuttihum P, de Souza M, Duerr A, Morgan C, Gilmour JWAdenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition. AIDS 2016;30(11):1703-12 doi: 10.1097/QAD.0000000000001122

Abstract & Topics (Click to display abstract, topics and IAVI Projects)    

The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers.

Page 16 of 92

StartPrev111213...1516171819...NextEnd

About

About

Board of Directors

Senior Leadership

Financial Statements

Global Funding & Support

Our History: 1995-2021

Our Work

Our Work

Discovery & Research

Translation & Product Development

Global Access to Scientific Innovations

ADVANCE

Advocacy & Community Engagement

Our Science

Our Science

Pipeline

HIV Vaccines

bnAbs for HIV Prevention

Tuberculosis Vaccines

Emerging Infectious Diseases Vaccines

News & Resources

Latest NewsLatest News

Scientific Publications Scientific Publications

Press Releases

Features

IAVI Report

IAVI in the News

Fact Sheets & Publications

VOICES Newsletter

Multimedia

Media Contacts

Subscribe

icon iaviIAVI guidestar platinum seal 2021 IAVI Charity Navigator 2021

Accessibility

Compliance/RFPs

Contact IAVI

Privacy Policy

Site Map

Supplier Diversity

Terms of Use

©2022 International AIDS Vaccine Initiative. International AIDS Vaccine Initiative®, IAVI®, and the IAVI logo® are registered trademarks of the International AIDS Vaccine Initiative, Inc.