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Title: Polyvalent vaccine approaches to combat HIV-1 diversity

Abstract

In this study, a key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversity, and outline the rationale behind several polyvalent vaccine design strategies that are currently under evaluation. Vaccine-elicited T-cell responses, which contribute to the control of HIV-1 in natural infections, are currently being considered in both prevention and treatment settings. Approaches now in preclinical and human trials include full proteins in novel vectors, concatenated conserved protein regions, and polyvalent strategies that improve coverage of epitope diversity and enhance the cross-reactivity of responses. While many barriers to vaccine induction of broadly neutralizing antibody (bNAb) responses remain, epitope diversification has emerged as both a challenge and an opportunity. Recent longitudinal studies have traced the emergence of bNAbs in HIV-1 infection, inspiring novel approaches to recapitulate and accelerate the events that give rise to potent bNAb in vivo. In this review, we have selected two such lineage-based design strategies to illustrate how such in-depth analysis can offer conceptual improvements that may bring us closer tomore » an effective vaccine.« less

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [2];  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Univ. of Pennsylvania, Philadelphia, PA (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1346839
Report Number(s):
LA-UR-16-26755
Journal ID: ISSN 0105-2896
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Immunological Reviews
Additional Journal Information:
Journal Volume: 275; Journal Issue: 1; Journal ID: ISSN 0105-2896
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Biological Science; AIDS; antibodies; antigens/peptides/epitopes; B cells; vaccination; viral

Citation Formats

Korber, Bette, Hraber, Peter Thomas, Wagh, Kshitij, and Hahn, Beatrice H. Polyvalent vaccine approaches to combat HIV-1 diversity. United States: N. p., 2017. Web. https://doi.org/10.1111/imr.12516.
Korber, Bette, Hraber, Peter Thomas, Wagh, Kshitij, & Hahn, Beatrice H. Polyvalent vaccine approaches to combat HIV-1 diversity. United States. https://doi.org/10.1111/imr.12516
Korber, Bette, Hraber, Peter Thomas, Wagh, Kshitij, and Hahn, Beatrice H. Mon . "Polyvalent vaccine approaches to combat HIV-1 diversity". United States. https://doi.org/10.1111/imr.12516. https://www.osti.gov/servlets/purl/1346839.
@article{osti_1346839,
title = {Polyvalent vaccine approaches to combat HIV-1 diversity},
author = {Korber, Bette and Hraber, Peter Thomas and Wagh, Kshitij and Hahn, Beatrice H.},
abstractNote = {In this study, a key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversity, and outline the rationale behind several polyvalent vaccine design strategies that are currently under evaluation. Vaccine-elicited T-cell responses, which contribute to the control of HIV-1 in natural infections, are currently being considered in both prevention and treatment settings. Approaches now in preclinical and human trials include full proteins in novel vectors, concatenated conserved protein regions, and polyvalent strategies that improve coverage of epitope diversity and enhance the cross-reactivity of responses. While many barriers to vaccine induction of broadly neutralizing antibody (bNAb) responses remain, epitope diversification has emerged as both a challenge and an opportunity. Recent longitudinal studies have traced the emergence of bNAbs in HIV-1 infection, inspiring novel approaches to recapitulate and accelerate the events that give rise to potent bNAb in vivo. In this review, we have selected two such lineage-based design strategies to illustrate how such in-depth analysis can offer conceptual improvements that may bring us closer to an effective vaccine.},
doi = {10.1111/imr.12516},
journal = {Immunological Reviews},
number = 1,
volume = 275,
place = {United States},
year = {2017},
month = {1}
}

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Works referenced in this record:

Designing and Testing Broadly-Protective Filoviral Vaccines Optimized for Cytotoxic T-Lymphocyte Epitope Coverage
journal, October 2012


A Multi-Component Prime-Boost Vaccination Regimen with a Consensus MOMP Antigen Enhances Chlamydia trachomatis Clearance
journal, April 2016

  • Badamchi-Zadeh, Alexander; McKay, Paul F.; Korber, Bette T.
  • Frontiers in Immunology, Vol. 7
  • DOI: 10.3389/fimmu.2016.00162

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence
journal, July 2016

  • Murray, Alexandra J.; Kwon, Kyungyoon J.; Farber, Donna L.
  • The Journal of Immunology, Vol. 197, Issue 2
  • DOI: 10.4049/jimmunol.1600343

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
journal, June 2009

  • Goonetilleke, Nilu; Liu, Michael K. P.; Salazar-Gonzalez, Jesus F.
  • The Journal of Experimental Medicine, Vol. 206, Issue 6
  • DOI: 10.1084/jem.20090365

Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
journal, November 2013

  • Hammer, Scott M.; Sobieszczyk, Magdalena E.; Janes, Holly
  • New England Journal of Medicine, Vol. 369, Issue 22
  • DOI: 10.1056/NEJMoa1310566

Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
journal, September 2012


Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques
journal, May 2016

  • Li, Hui; Wang, Shuyi; Kong, Rui
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 24
  • DOI: 10.1073/pnas.1606636113

Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection
journal, March 2016


Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains
journal, June 2014

  • Fera, D.; Schmidt, A. G.; Haynes, B. F.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 28
  • DOI: 10.1073/pnas.1409954111

Cytomegalovirus Vectors Violate CD8+ T Cell Epitope Recognition Paradigms
journal, May 2013


Justification for the inclusion of Gag in HIV vaccine candidates
journal, December 2015


Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine
journal, October 2007


T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces
journal, May 2009

  • Korber, B. T.; Letvin, N. L.; Haynes, B. F.
  • Journal of Virology, Vol. 83, Issue 17, p. 8300-8314
  • DOI: 10.1128/JVI.00114-09

Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys
journal, February 2010

  • Santra, Sampa; Liao, Hua-Xin; Zhang, Ruijin
  • Nature Medicine, Vol. 16, Issue 3, p. 324-328
  • DOI: 10.1038/nm.2108

Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer
journal, September 2015

  • Kong, Leopold; Torrents de la Peña, Alba; Deller, Marc C.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 10
  • DOI: 10.1107/S1399004715013917

Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial
journal, April 2012

  • Haynes, Barton F.; Gilbert, Peter B.; McElrath, M. Juliana
  • New England Journal of Medicine, Vol. 366, Issue 14
  • DOI: 10.1056/NEJMoa1113425

The role of recombination in the emergence of a complex and dynamic HIV epidemic
journal, March 2010


Protective Efficacy of a Global HIV-1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys
journal, October 2013


Persistent HIV-1 replication during antiretroviral therapy
journal, January 2016


HIV-1 Conserved Elements p24CE DNA Vaccine Induces Humoral Immune Responses with Broad Epitope Recognition in Macaques
journal, October 2014


A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies
journal, September 2013


Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens
journal, March 2016

  • Hessell, Ann J.; Malherbe, Delphine C.; Pissani, Franco
  • The Journal of Immunology, Vol. 196, Issue 7
  • DOI: 10.4049/jimmunol.1500527

Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape
journal, May 2012


Optimization and delivery of plasmid DNA for vaccination
journal, December 2006


HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996


New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency
journal, October 2015

  • Doria-Rose, Nicole A.; Bhiman, Jinal N.; Roark, Ryan S.
  • Journal of Virology, Vol. 90, Issue 1
  • DOI: 10.1128/JVI.01791-15

Definition of the viral targets of protective HIV-1-specific T cell responses
journal, January 2011

  • Mothe, Beatriz; Llano, Anuska; Ibarrondo, Javier
  • Journal of Translational Medicine, Vol. 9, Issue 1
  • DOI: 10.1186/1479-5876-9-208

Nanoparticle vaccines
journal, January 2014


Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein
journal, June 2015


HIV-1 Nomenclature Proposal
journal, April 2000


Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study
journal, May 2015


Novel Conserved-region T-cell Mosaic Vaccine With High Global HIV-1 Coverage Is Recognized by Protective Responses in Untreated Infection
journal, April 2016

  • Ondondo, Beatrice; Murakoshi, Hayato; Clutton, Genevieve
  • Molecular Therapy, Vol. 24, Issue 4
  • DOI: 10.1038/mt.2016.3

Immune System Regulation in the Induction of Broadly Neutralizing HIV-1 Antibodies
journal, December 2013


Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design
journal, December 2015

  • Gorman, Jason; Soto, Cinque; Yang, Max M.
  • Nature Structural & Molecular Biology, Vol. 23, Issue 1
  • DOI: 10.1038/nsmb.3144

Recent Developments in Preclinical DNA Vaccination
journal, January 2014


Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques
journal, August 2015


Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
journal, April 2013

  • Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing
  • Nature, Vol. 496, Issue 7446
  • DOI: 10.1038/nature12053

Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition
journal, February 2016

  • Abdul-Jawad, Sultan; Ondondo, Beatrice; van Hateren, Andy
  • Molecular Therapy, Vol. 24, Issue 2
  • DOI: 10.1038/mt.2015.210

Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies
journal, October 2015

  • Bhiman, Jinal N.; Anthony, Colin; Doria-Rose, Nicole A.
  • Nature Medicine, Vol. 21, Issue 11
  • DOI: 10.1038/nm.3963

Mosaic H5 Hemagglutinin Provides Broad Humoral and Cellular Immune Responses against Influenza Viruses
journal, May 2016

  • Kamlangdee, Attapon; Kingstad-Bakke, Brock; Osorio, Jorge E.
  • Journal of Virology, Vol. 90, Issue 15
  • DOI: 10.1128/JVI.00730-16

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody
journal, April 2016


Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E
journal, January 2016


Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design
journal, March 2013


Antibody responses to envelope glycoproteins in HIV-1 infection
journal, May 2015

  • Burton, Dennis R.; Mascola, John R.
  • Nature Immunology, Vol. 16, Issue 6
  • DOI: 10.1038/ni.3158

Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants
journal, December 2006

  • Fischer, Will; Perkins, Simon; Theiler, James
  • Nature Medicine, Vol. 13, Issue 1, p. 100-106
  • DOI: 10.1038/nm1461

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys
journal, November 2008

  • Liu, Jinyan; O’Brien, Kara L.; Lynch, Diana M.
  • Nature, Vol. 457, Issue 7225
  • DOI: 10.1038/nature07469

Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
journal, December 2009

  • Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai
  • New England Journal of Medicine, Vol. 361, Issue 23
  • DOI: 10.1056/NEJMoa0908492

Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies
journal, August 2016


Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01
journal, July 2010


Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study
journal, May 2014


Distinct Evolutionary Pressures Underlie Diversity in Simian Immunodeficiency Virus and Human Immunodeficiency Virus Lineages
journal, October 2012

  • Fischer, W.; Apetrei, C.; Santiago, M. L.
  • Journal of Virology, Vol. 86, Issue 24
  • DOI: 10.1128/JVI.01862-12

Hepatitis C Genotype 1 Mosaic Vaccines Are Immunogenic in Mice and Induce Stronger T-Cell Responses than Natural Strains
journal, December 2012

  • Yusim, Karina; Dilan, Rebecca; Borducchi, Erica
  • Clinical and Vaccine Immunology, Vol. 20, Issue 2
  • DOI: 10.1128/CVI.00605-12

Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G
journal, May 2016


Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies
journal, July 2014


Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV
journal, December 2013

  • Roederer, Mario; Keele, Brandon F.; Schmidt, Stephen D.
  • Nature, Vol. 505, Issue 7484
  • DOI: 10.1038/nature12893

Early Selection in Gag by Protective HLA Alleles Contributes to Reduced HIV-1 Replication Capacity That May Be Largely Compensated for in Chronic Infection
journal, September 2010

  • Brockman, Mark A.; Brumme, Zabrina L.; Brumme, Chanson J.
  • Journal of Virology, Vol. 84, Issue 22
  • DOI: 10.1128/JVI.01086-10

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants
journal, October 2015

  • Hraber, Peter; Korber, Bette; Wagh, Kshitij
  • Viruses, Vol. 7, Issue 10
  • DOI: 10.3390/v7102881

Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys
journal, February 2010

  • Barouch, Dan H.; O'Brien, Kara L.; Simmons, Nathaniel L.
  • Nature Medicine, Vol. 16, Issue 3, p. 319-323
  • DOI: 10.1038/nm.2089

Antiretroviral Treatment of Adult HIV Infection: 2014 Recommendations of the International Antiviral Society–USA Panel
journal, July 2014

  • Günthard, Huldrych F.; Aberg, Judith A.; Eron, Joseph J.
  • JAMA, Vol. 312, Issue 4
  • DOI: 10.1001/jama.2014.8722

Nanotechnology in vaccine delivery
journal, May 2008

  • Peek, Laura J.; Middaugh, C. Russell; Berkland, Cory
  • Advanced Drug Delivery Reviews, Vol. 60, Issue 8
  • DOI: 10.1016/j.addr.2007.05.017

Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing
journal, August 2010


HIV-1 Vaccine Development After STEP
journal, February 2010


Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine
journal, May 2011

  • Hansen, Scott G.; Ford, Julia C.; Lewis, Matthew S.
  • Nature, Vol. 473, Issue 7348
  • DOI: 10.1038/nature10003

Impact of HIV infection on the haemostatic response during sepsis and malaria
journal, March 2016

  • Huson, Michaëla A. M.; Kalkman, Rachel; Hoogendijk, Arie J.
  • British Journal of Haematology, Vol. 173, Issue 6
  • DOI: 10.1111/bjh.14006

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors
journal, June 2015


Progress in HIV-1 vaccine development
journal, July 2014

  • Haynes, Barton F.; Moody, M. Anthony; Alam, Munir
  • Journal of Allergy and Clinical Immunology, Vol. 134, Issue 1
  • DOI: 10.1016/j.jaci.2014.04.025

Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120
journal, May 2013

  • Kong, Leopold; Lee, Jeong Hyun; Doores, Katie J.
  • Nature Structural & Molecular Biology, Vol. 20, Issue 7
  • DOI: 10.1038/nsmb.2594

Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale
journal, August 2014


Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing
journal, August 2011


Vaccine delivery using nanoparticles
journal, January 2013

  • Gregory, Anthony E.; Titball, Richard; Williamson, Diane
  • Frontiers in Cellular and Infection Microbiology, Vol. 3
  • DOI: 10.3389/fcimb.2013.00013

Antiretroviral Therapy for the Prevention of HIV-1 Transmission
journal, September 2016

  • Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth
  • New England Journal of Medicine, Vol. 375, Issue 9
  • DOI: 10.1056/NEJMoa1600693

Breadth of cellular and humoral immune responses elicited in rhesus monkeys by multi-valent mosaic and consensus immunogens
journal, July 2012


Web-based design and evaluation of T-cell vaccine candidates
journal, May 2008


Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine
journal, October 2016

  • Theiler, James; Yoon, Hyejin; Yusim, Karina
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep33987

Diversity Considerations in HIV-1 Vaccine Selection
journal, June 2002

  • Gaschen, Brian; Taylor, Jesse; Yusim, Karina
  • Science, Vol. 296, Issue 5577, p. 2354-2360
  • DOI: 10.1126/science.1070441

Polyreactivity and Autoreactivity among HIV-1 Antibodies
journal, October 2014

  • Liu, Mengfei; Yang, Guang; Wiehe, Kevin
  • Journal of Virology, Vol. 89, Issue 1
  • DOI: 10.1128/JVI.02378-14

T cells induced by recombinant chimpanzee adenovirus alone and in prime-boost regimens decrease chimeric EcoHIV/NDK challenge virus load: Immunity to infection
journal, October 2012

  • Roshorm, Yaowaluck; Cottingham, Mathew G.; Potash, Mary-Jane
  • European Journal of Immunology, Vol. 42, Issue 12
  • DOI: 10.1002/eji.201242624

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    T = 4 Icosahedral HIV-1 Capsid As an Immunogenic Vector for HIV-1 V3 Loop Epitope Display
    journal, November 2018

    • Zhang, Zhiqing; He, Maozhou; Bai, Shimeng
    • Viruses, Vol. 10, Issue 12
    • DOI: 10.3390/v10120667

    The quest for an antibody-based HIV vaccine
    journal, January 2017

    • Haynes, Barton F.; Mascola, John R.
    • Immunological Reviews, Vol. 275, Issue 1
    • DOI: 10.1111/imr.12517

    Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
    journal, August 2019

    • Rudometov, Andrey P.; Chikaev, Anton N.; Rudometova, Nadezhda B.
    • Vaccines, Vol. 7, Issue 3
    • DOI: 10.3390/vaccines7030083

    Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants
    journal, July 2018


    Simplified steps to heterologous prime-boost HIV vaccine development?
    journal, September 2019

    • Michael, Nelson L.
    • Journal of Clinical Investigation, Vol. 129, Issue 11
    • DOI: 10.1172/jci132440

    Models of immune selection for multi-locus antigenic diversity of pathogens
    journal, November 2018

    • Georgieva, Maria; Buckee, Caroline O.; Lipsitch, Marc
    • Nature Reviews Immunology, Vol. 19, Issue 1
    • DOI: 10.1038/s41577-018-0092-5

    Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
    journal, May 2019


    Nanoparticle vaccines against viral infections
    journal, May 2018

    • Sulczewski, Fernando B.; Liszbinski, Raquel B.; Romão, Pedro R. T.
    • Archives of Virology, Vol. 163, Issue 9
    • DOI: 10.1007/s00705-018-3856-0

    A novel polyepitope vaccine elicited HIV peptide specific CD4+ T cell responses in HLA-A2/DRB1 transgenic mice
    journal, September 2017