• Careers
  • Contact Us
  • Donate
  • Search

Logo

  • About
  • Our Work
  • Our Science
  • Newsroom
    • Scientific Publications
    • Press Releases
    • IAVI in the News
    • More News
    • Fact Sheets & Publications
    • IAVI Report
    • VOICES
Home > Newsroom > Scientific Publications

Scientific Publications

Filter By:

 

 
Filters

Ford T, Wenden C, Mbekeani A, Dally L, Cox JH, Morin M, Winstone N, Hill AVS, Gilmour J, Ewer KJCryopreservation-related loss of antigen-specific IFNγ producing CD4 T-cells can skew immunogenicity data in vaccine trials: Lessons from a malaria vaccine trial substudy. Vaccine 2017;35(15):1898-1906 doi: S0264-410X(17)30241-4

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

Ex vivo functional immunoassays such as ELISpot and intracellular cytokine staining (ICS) by flow cytometry are crucial tools in vaccine development both in the identification of novel immunogenic targets and in the immunological assessment of samples from clinical trials. Cryopreservation and subsequent thawing of PBMCs via validated processes has become a mainstay of clinical trials due to processing restrictions inherent in the disparate location and capacity of trial centres, and also in the need to standardize biological assays at central testing facilities. Logistical and financial requirement to batch process samples from multiple study timepoints are also key. We used ELISpot and ICS assays to assess antigen-specific immunogenicity in blood samples taken from subjects enrolled in a phase II malaria heterologous prime-boost vaccine trial and showed that the freeze thaw process can result in a 3-5-fold reduction of malaria antigen-specific IFNγ-producing CD3CD4 effector populations from PBMC samples taken post vaccination. We have also demonstrated that peptide responsive CD8 T cells are relatively unaffected, as well as CD4 T cell populations that do not produce IFNγ. These findings contribute to a growing body of data that could be consolidated and synthesised as guidelines for clinical trials with the aim of increasing the efficiency of vaccine development pipelines.

Wu KY, Oppert M, Wall KM, Inambao M, Simpungwe MK, Ahmed N, Abdallah JF, Tichacek A, Allen SACouples' voluntary HIV counseling and testing provider training evaluation, Zambia. Health Promot Int 2017; doi: daw108

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

With the expansion of couples' voluntary HIV counseling and testing (CVCT) in urban Zambia, there is a growing need to evaluate CVCT provider trainings to ensure that couples are receiving quality counseling and care. We evaluated provider knowledge scores, pre- and post-training and predictors of pre- and post-training test scores. Providers operating in 67 government clinics in four Copperbelt Province cities were trained from 2008 to 2013 in three domains: counseling, rapid HIV laboratory testing and data management. Trainees received pre- and post-training tests on domain-specific topics. Pre- and post-training test scores were tabulated by provider demographics and training type, and paired t-tests evaluated differences in pre- and post-training test scores. Multivariable ANCOVA determined predictors of pre- and post-training test scores. We trained 1226 providers, and average test scores increased from 68.8% pre-training to 83.8% post-training (p < 0.001). Test scores increased significantly for every demographic group and training type (p < 0.001) with one exception-test scores did not significantly increase for those receiving counseling or data management training who had less than a high school education. In multivariable analysis, higher educational level and having a medical background were predictive of a higher pre-test score; higher pre-test scores and having a medical background were predictive of higher post-test scores. Pre- and post-test assessments are critical to ensure quality services, particularly as task-shifting from medical to lay staff becomes more common. Assessments showed that our CVCT trainings are successful at increasing knowledge, and that those with lower education may benefit from repeat trainings.

Landais E, Murrell B, Briney B, Murrell S, Rantalainen K, Berndsen ZT, Ramos A, Wickramasinghe L, Smith ML, Eren K, de Val N, Wu M, Cappelletti A, Umotoy J, Lie Y, Wrin T, Algate P, Chan-Hui PY, Karita E, Ward AB, Wilson IA, Burton DR, Smith D, Pond SLK, Poignard P

HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage. Immunity 2017;47(5):990-1003.e9 doi: S1074-7613(17)30479-X

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

Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.

Topics: HIV Immunogen Design

Grebe E, Welte A, Hall J, Keating SM, Facente SN, Marson K, Martin JN, Little SJ, Price MA, Kallas EG, Busch MP, Pilcher CD, Murphy GInfection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms. J. Acquir. Immune Defic. Syndr. 2017;76(5):547-555 doi: 10.1097/QAI.0000000000001537

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

Custom HIV staging assays, including the Sedia HIV-1 Limiting Antigen (LAg) Avidity EIA and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify 'recent' infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and long-standing infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.

Ingale J, Stano A, Guenaga J, Sharma SK, Nemazee D, Zwick MB, Wyatt RTHigh-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells. Cell Rep 2016;15(9):1986-99 doi: 10.1016/j.celrep.2016.04.078

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

A major step toward an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env) mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers. Here, we present the design of liposomal nanoparticles displaying well-ordered Env spike trimers on their surface. Biophysical analysis, cryo- and negative stain electron microscopy, as well as binding analysis with a panel of broadly neutralizing antibodies confirm a high-density, well-ordered trimer particulate array. The Env-trimer-conjugated liposomes were superior to soluble trimers in activating B cells ex vivo and germinal center B cells in vivo. In addition, the trimer-conjugated liposomes elicited modest tier 2 homologous neutralizing antibodies. The trimer-conjugated liposomes represent a promising initial lead toward the development of more effective HIV vaccine immunogens.

Rutstein SE, Ananworanich J, Fidler S, Johnson C, Sanders EJ, Sued O, Saez-Cirion A, Pilcher CD, Fraser C, Cohen MS, Vitoria M, Doherty M, Tucker JD

Clinical and public health implications of acute and early HIV detection and treatment: a scoping review. J Int AIDS Soc 2017;20(1):21579 doi: 10.7448/IAS.20.1.21579

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

The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.

Topics: HIV Acute Infection

McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, Kulp DW, Macauley MS, Sok D, Pauthner M, Menis S, Cottrell CA, Torres JL, Hsueh J, Schief WR, Wilson IA, Ward AB, Sanders RW, Burton DRHoles in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies. Cell Rep 2016;16(9):2327-38 doi: 10.1016/j.celrep.2016.07.074

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

A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design.

Wang Y, O'Dell S, Turner HL, Chiang CI, Lei L, Guenaga J, Wilson R, Martinez-Murillo P, Doria-Rose N, Ward AB, Mascola JR, Wyatt RT, Karlsson Hedestam GB, Li Y

HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates. J. Virol. 2017;91(21) doi: e00910-17

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

Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation. Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within a subset of individuals. To achieve this goal, an improved understanding of vaccine-elicited responses, including at the monoclonal Ab level, is essential. Here, we isolated and characterized a panel of vaccine-elicited cross-reactive neutralizing MAbs targeting the Env V3 loop that moderately neutralized several primary viruses and recapitulated the serum neutralizing antibody response. Striking similarities between the cross-reactive V3 NAbs elicited by vaccination in macaques and natural infections in humans illustrate commonalities between the vaccine- and infection-induced responses to V3 and support the feasibility of exploring the V3 epitope as a HIV-1 vaccine target in nonhuman primates.

Topics: HIV Immunogen Design, HIV Neutralizing Antibodies

Burton DR, Hangartner LBroadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol. 2016;34:635-59 doi: 10.1146/annurev-immunol-041015-055515

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

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.

Sok D, Burton DR

HIV Broadly Neutralizing Antibodies: Taking Good Care Of The 98. Immunity 2016;45(5):958-960 doi: S1074-7613(16)30444-7

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

In this issue of Immunity, Huang et al. (2016) describe an exceptionally broad and potent neutralizing antibody to HIV. This antibody, N6, is capable of neutralizing up to 98% of global isolates with a potent median IC of 0.04 μg/mL, making it the current 'best-in-class' for bNAbs targeting the CD4 binding site.

Topics: HIV Neutralizing Antibodies

Page 9 of 84

StartPrev...56789...111213NextEnd

About

Board of Directors

Senior Leadership

Financial Statements

Global Funding & Support

Our Work

Discovery

Translation & Product Development

Clinical & Epidemiology Research

Global Community Engagement

IAVI DataSpace

Our Science

Pipeline

Broadly Neutralizing Antibodies

Immunogens

Viral Vectors and mRNA

Tuberculosis

Other Diseases

Newsroom

Scientific Publications

Press Releases

IAVI in the News

More News

Fact Sheets & Publications

IAVI Report

VOICES

Accessibility

Compliance

Contact Us

Privacy Policy

Site Map

Supplier Diversity

Terms of Use

©2018 International AIDS Vaccine Initiative. All rights reserved. International AIDS Vaccine Initiative, IAVI, and the IAVI logo
are trademarks of the International AIDS Vaccine Initiative, Inc.