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Design and tests of an HIV vaccine.

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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.

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Journal ArticleDOI

Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II.

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.
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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.
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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

Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen.

TL;DR: Adoptive transfer experiments of immune spleen cells into syngeneic recipients without addition of antigen demonstrated that maintenance of the antiviral protective capacity of the transferred cells depended on the presence of viral antigen.

Antivirally Protective Cytotoxic T Cell Memory to Lymphocytic Choriomeningitis Virus Is Governed by

TL;DR: The basis of antiviral protection by memory cytotoxic T lymphocytes (CTL) was investigated in vivo and in vitro using lymphocytic choriomeningitis virus (LCMV) and recombinant vaccinia viruses expressing the LCMVglycoprotein (vacc-GP) or -nucleoprotein(vacc-NP) as discussed by the authors.
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T Cell Receptor Repertoire for a Viral Epitope in Humans Is Diversified by Tolerance to a Background Major Histocompatibility Complex Antigen

TL;DR: Tolerance to a background major histocompatibility antigen can effectively diversify the TCR repertoire for a foreign epitope by deflecting the response away from an immunodominant combination of TCR-binding residues.
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T cell responses and viral escape.

TL;DR: In long-term HIV-infected patients, it is striking that very strong CTL responses are maintained despite the loss of specific Th cells, and a coordinated attack on more than one, coupled with effective control of virus replication by potent drug combinations, offers hope of effective therapeutic assistance to the CTL in controlling HIV infection.
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Antagonist HIV-1 Gag peptides induce structural changes in HLA B8.

TL;DR: This work characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24–31) exhibit a variety of responses, and examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface.
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