Design and tests of an HIV vaccine.
TLDR
Experiments in macaques and man suggest that a prime boost regimen using DNA and recombinant pox virus is highly effective at stimulating cellular immunity, but the difficulty of inducing broad cellular responses able to protect against all clades of HIV, remains an important issue.Abstract:
It is likely that a successful vaccine against HIV will need to stimulate the innate immune system, generate high levels of neutralising antibody, strong cellular immune responses, and mucosal immunity. Early efforts to develop HIV vaccines attempted to use the virus glycoprotein, gp120, to induce neutralising antibody, but did not take into account the trimeric structure of the native glycoprotein or the complex nature of the CD4 and chemokine receptor binding sites. Recently, attention has been focused on cellular immune responses, particularly T-cell cytotoxicity, based on evidence from the SIV model and from exposed and uninfected humans. Recent experiments in macaques and man suggest that a prime boost regimen using DNA and recombinant pox virus is highly effective at stimulating cellular immunity. However, in addition to the problems of generating neutralising antibodies and mucosal immunity, the difficulty of inducing broad cellular responses able to protect against all clades of HIV, remains an important issue.read more
Citations
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Journal ArticleDOI
Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities
Nicole Frahm,Bette T. Korber,Bette T. Korber,C. M. Adams,James J. Szinger,Rika Draenert,Marylyn M. Addo,Margaret E. Feeney,Karina Yusim,Kaori Sango,Nancy V. Brown,Devi SenGupta,Alicja Piechocka-Trocha,T. Simonis,F. M. Marincola,Alysse G. Wurcel,David Stone,Christopher J. Russell,P. Adolf,Daniel E. Cohen,Timothy Roach,A. StJohn,Ashok Khatri,K. Davis,James I. Mullins,Philip J. R. Goulder,Bruce D. Walker,Christian Brander +27 more
TL;DR: Factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations are identified.
Journal ArticleDOI
Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II.
Devi SenGupta,Philip J. Norris,Todd J. Suscovich,Mina Hassan-Zahraee,Howell F. Moffett,Alicja Trocha,Rika Draenert,Philip J. R. Goulder,Robert J. Binder,Daniel L. Levey,Bruce D. Walker,Pramod K. Srivastava,Christian Brander +12 more
TL;DR: The present data suggest that HSP-complexed peptides containing multiple MHC class I- and class II-restricted epitopes represent potential vaccine candidates for HIV and other viral infections suitable to induce effective CTL memory by simultaneously providing CD4 T cell help.
Journal ArticleDOI
Causal Vaccine Effects on Binary Postinfection Outcomes
TL;DR: The results show that pertussis vaccination has a significant causal effect in reducing disease severity and the relations between the MLE of the causal estimand and two commonly used estimators for vaccine effects on postinfection outcomes are shown.
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A comparative analysis of viral matrix proteins using disorder predictors
TL;DR: Analysis of the PID patterns in matrix proteins of viruses related and unrelated to HIV-1 might have important implications in the search for HIV vaccines since disorder in the matrix protein might provide a mechanism for immune evasion.
Journal ArticleDOI
Protein intrinsic disorder toolbox for comparative analysis of viral proteins
TL;DR: This exercise provides an example showing how the combined use of intrinsic disorder predictions and relational databases provides an improved understanding of the functional and structural behaviour of viral proteins.
References
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Journal ArticleDOI
Immunological and Virological Analyses of Persons Infected by Human Immunodeficiency Virus Type 1 while Participating in Trials of Recombinant gp120 Subunit Vaccines
Ruth I. Connor,Bette T. Korber,Barney S. Graham,Beatrice H. Hahn,David D. Ho,Bruce D. Walker,Avidan U. Neumann,Sten H. Vermund,Jiri Mestecky,Susan Jackson,Elizabeth A. Fenamore,Yunzhen Cao,Feng Gao,Spyros A. Kalams,Kevin J. Kunstman,D. McDonald,N. McWilliams,Alexandra Trkola,John P. Moore,Steven M. Wolinsky +19 more
TL;DR: It is concluded that vaccination with rgp120 has had, to date, no obvious beneficial or adverse effects on the individuals the authors have studied and genetic sequencing of the envgenes of strains infecting the vaccinees did not reveal any features that clearly distinguished these viruses from contemporary clade B viruses circulating in the United States.
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MVA vaccination against smallpox: clinical tests with an attenuated live vaccinia virus strain (MVA).
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MVA-Stufenimpfung gegen Pocken
Journal ArticleDOI
Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques
Awen Gallimore,Martin Cranage,Nancy R. Cook,Neil Almond,Janet S. Bootman,Erling W. Rud,P. Silvera,Michael Dennis,T. Corcoran,Jim Stott +9 more
TL;DR: Using the macaque simian immunodeficiency virus (SIV) model, the protective potential of nef-specific CTLs, stimulated by vaccination, was examined in animals challenged with a high intravenous dose of the pathogenic simian vaccine-induced SIVmac251(32H)(pJ5).
Journal ArticleDOI
Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.
Tomáš Hanke,Andrew J. McMichael +1 more
TL;DR: A new candidate human immunodeficiency virus (HIV) vaccine has been developed and tailor-designed for a phase III clinical trial in Kenya, and focuses on the induction of cell-mediated immune responses.
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